EDITORIAL ESPANOL:

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Hola amigos DERMÁGICOS, allí va la segunda parte de la revisión sobre LUPUS ERITEMATOSO SISTÉMICO, el tema es muy amplio y seleccione las mejores de los años 97-99. y se actualizo 2024 haciendo énfasis en el tratamiento.

Nos volveremos a ver en la red...PRÓXIMA EDICIÓN: DERMATOMIOSITIS.

Saludos,,,

Dr. José Lapenta R.,,,

 EDITORIAL ENGLISH:

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Hello DERMAGICS friends, there goes the second part of the revision SYSTEMIC LUPUS ERYTHEMATOSUS, the topic is very wide and select the best in the years 97-99. and it was update in 2024 emphasizing treatment.

We will see in the net again...NEXT EDITION: DERMATOMYOSITIS. 

Greetings,,,

Dr. José Lapenta R. 

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DERMAGIC/EXPRESS(54)

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LUPUS ERITEMATOSO SISTÉMICO II/ SYSTEMIC LUPUS ERYTHEMATOSUS II

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A.) New and Emerging Therapies for Systemic Lupus Erythematosus.

B.) Emerging Biologic Therapies for Systemic Lupus Erythematosus.

C.) Biologics in Systemic Lupus Erythematosus: Recent Evolutions and Benefits.

D.) New and Future Therapies: Changes in the Therapeutic Armamentarium for SLE.

E.) Targeted Small Molecules for Systemic Lupus Erythematosus: Drugs in the Pipeline.

F.) Current Cell Therapies for Systemic Lupus Erythematosus.

G.) New Developments in Systemic Lupus Erythematosus.

H.) First Latin American Clinical Practice Guidelines for the Treatment of Systemic Lupus Erythematosus: Latin American Group for the Study of Lupus (GLADEL, Grupo Latino Americano De Estudio Del Lupus)-Pan-American League of Associations of Rheumatology (PANLAR).

I.) Treating Systemic Lupus Erythematosus in the 21st Century: New Drugs and New Perspectives on Old Drugs.

J.) Systemic Lupus Erythematosus: A Review.

K.) Systemic Lupus Erythematosus: Diagnosis and Treatment.

52.) [Soluble tumor necrosis factor receptors in patients with systemic lupus erythematosus] 

53.) Primary biliary cirrhosis and systemic lupus erythematosus. A new case report. 

54.) Genetic analysis of interleukin-10 promoter region in patients with systemic lupus erythematosus in Taiwan. 

55.) Mucocutaneous disease in Arabs with systemic lupus erythematosus: clinical expression and relevance to autoantibodies. 

56.) Renal transplantation in systemic lupus erythematosus. A case control study of 45 patients. 

57.) Salmonella septic arthritis in systemic lupus erythematosus and other systemic diseases. 

58.) Neuropsychiatric systemic lupus erythematosus and the syndrome of inappropriate secretion of antidiuretic hormone: a case report with very late onset systemic lupus erythematosus. 

59.) Myocardial infarction in patients with systemic lupus erythematosus with normal findings from coronary arteriography and without coronary vasculitis--case reports. 

60.) [Is autoantibody determination in patients with systemic lupus erythematosus useful? Anti-C1q-autoantibody as an example] 

61.) Association between prolactin and disease activity in systemic lupus erythematosus. Influence of statistical power. 

62.) Correlation of 9G4 idiotope with disease activity in patients with systemic lupus erythematosus. 

63.) Systemic lupus erythematosus: perinatal and neonatal implications. 

64.) Autologous peripheral blood stem and progenitor (CD34+) cell transplantation for systemic lupus erythematosus complicated by Evans syndrome. 

65.) [Evolutive aspects of systemic lupus erythematosus in Dakar. Apropos of 30 cases] 

66.) Autoantibodies in systemic lupus erythematosus. 

67.) The genetics of human systemic lupus erythematosus. 

68.) Exacerbation of systemic lupus erythematosus related to cytomegalovirus infection. 

69.) Visual disturbance by lymphocytic hypophysitis in a non-pregnant woman with systemic lupus erythematosus. 

70.) Pulmonary involvement in juvenile systemic lupus erythematosus: a study on lung function in patients asymptomatic for respiratory disease. 

71.) Genome scan of human systemic lupus erythematosus: evidence for linkage on chromosome 1q in African-American pedigrees. 

72.) Cutaneous manifestations of childhood systemic lupus erythematosus. 

73.) Gender differences in autoimmune diseases: estrogen increases calcineurin expression in systemic lupus erythematosus. 

74.) Anti-beta2-glycoprotein I, anti-prothrombin and anticardiolipin antibodies in a longitudinal study of patients with systemic lupus erythematosus and the antiphospholipid syndrome. 

75.) Identification and characterization of a calreticulin-binding nuclear protein as histone (H1), an autoantigen in systemic lupus erythematosus. 

76.) Systemic lupus erythematosus in Kuwait--hospital based study. 

77.) Use of intravenous immunoglobulin therapy in pregnancy in systemic lupus erythematosus and antiphospholipid antibody syndrome. 

78.) Relationship between neurometabolite derangement and neurocognitive dysfunction in systemic lupus erythematosus. 

79.) Mutations in T cell receptor zeta chain mRNA of peripheral T cells from systemic lupus erythematosus patients. 

80.) C1q and systemic lupus erythematosus. 

81.) A multicentre study of 513 Danish patients with systemic lupus erythematosus. I. Disease manifestations and analyses of clinical subsets. 

82.) Renal manifestations of concurrent systemic lupus erythematosus and HIV infection. 

83.) Glomerular thrombosis: an unusual cause of renal failure in systemic lupus erythematosus. 

84.) Coexistent minocycline-induced systemic lupus erythematosus and autoimmune hepatitis. 

85.) Expression of CTLA-4 molecule in peripheral blood T lymphocytes from patients with systemic lupus erythematosus. 

86.) [Nasal reactivity in systemic lupus erythematosus] 

87.) Mycophenolate mofetil suppresses autoimmunity and mortality in the female NZB x NZW F1 mouse model of systemic lupus erythematosus. 

88.) Prevalence of autoantibodies to ribosomal P proteins in juvenile-onset systemic lupus erythematosus compared with the adult disease. 

89.) Trends in the incidence and mortality of systemic lupus erythematosus, 1950-1992. 

90.) Antithrombin, protein S and protein C and antiphospholipid antibodies in systemic lupus erythematosus. 

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51.) Dehydroepiandrosterone in systemic lupus erythematosus: relationship between dosage, serum levels, and clinical response. 

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Author 

Barry NN; McGuire JL; van Vollenhoven RF 

Address 

Division of Immunology and Rheumatology, Stanford University Medical Center, CA 94305-5111, USA. 

Source 

J Rheumatol, 25(12):2352-6 1998 Dec 

Abstract 

OBJECTIVE: To examine in women with systemic lupus erythematosus (SLE) who participated in a clinical trial the relationship between daily dose of dehydroepiandrosterone (DHEA), serum levels of DHEA and DHEA sulfate (DHEAS), clinical effectiveness, and side effects. METHODS: Twenty-three women with mild to moderate SLE were treated with DHEA for a 6 month period. The starting dose was 50 mg/day, and monthly stepwise increases were allowed. Subjects were assessed monthly by the Systemic Lupus Erythematosus Disease Activity Index, Systemic Lupus Activity Measure (SLAM), Health Assessment Questionnaire, and other outcomes. Serum testosterone, DHEA, and DHEAS levels were obtained and side effects noted monthly. RESULTS: Statistically significant improvements were found in all lupus outcomes over 6 months. Serum DHEA and DHEAS levels correlated with the dose of DHEA. Serum DHEA and DHEAS correlated negatively with SLAM score. A second order regression analysis of serum DHEAS level versus SLAM score suggested that the optimal serum level of DHEAS was 1000 microg/dl. The most common side effect was acne. CONCLUSION: The clinical response to DHEA was not clearly dose dependent. Serum levels of DHEA and DHEAS correlated only weakly with lupus outcomes, but suggested an optimum serum DHEAS of 1000 microg/dl. Monitoring these serum levels appears to have limited clinical utility. 

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52.) [Soluble tumor necrosis factor receptors in patients with systemic lupus erythematosus] 

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Author 

Weber JC; Korganow AS; Ginsbourger M; Lehr L; Hauptmann G; Muller S; Pasquali JL 

Address 

Service de M´edecine interne et d'Immunologie Clinique, H^opitaux Universitaires de Strasbourg. 

Source 

Presse Med, 27(38):1941-5 1998 Dec 5 

Abstract 

OBJECTIVE: To study the variations of type II soluble receptors for tumor necrosis factor (sR-TNF) in patients with systemic lupus erythematosus and investigate their use in the clinical setting. PATIENTS AND METHODS: Twenty-six patients with systemic lupus were followed for a mean 3 years. sR-TNF and other immunological parameters (C reactive protein, anti-DNA antibodies, C3 and C4 complement fractions, soluble receptors for interleukin 2) were measured in sera at different points of the disease course. The systemic lupus activity measure (SLAM) was determined at each point, and confronted with the biology results. The study was cross sectional for the group and longitudinal for the patients. RESULTS: sR-TNF was the immunological parameter which correlated best with SLAM. It also correlated with sedimentation rate, C reactive protein, thrombopenia, anemia, creatinine level, anti-DNA antibodies and sR-IL2. The longitudinal study pointed out however that this finding is not consistent for each patient. CONCLUSION: A rise in sR-TNF related to systemic lupus activity but is of limited practical interest for individual patient follow-up. 

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53.) Primary biliary cirrhosis and systemic lupus erythematosus. A new case report. 

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Author 

Michel F; Toussirot E; Wendling D 

Address 

Rheumatology Department, Jean Minjoz Teaching Hospital, Besan¸con, France. 

Source 

Rev Rhum Engl Ed, 65(7-9):504-7 1998 Jul-Sep 

Abstract 

Systemic lupus erythematosus and primary biliary cirrhosis are two autoimmune disorders that rarely occur in the same patient. Ten well-documented cases have been reported to date. We add the case of a woman who was diagnosed with systemic lupus erythematosus at 54 years of age then with primary biliary cirrhosis 18 years later. Interestingly, primary biliary cirrhosis antedated the systemic lupus erythematosus in all the other reported cases. The possibility that a patient may develop more than one autoimmune disorder should be borne in mind. 

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54.) Genetic analysis of interleukin-10 promoter region in patients with systemic lupus erythematosus in Taiwan. 

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Author 

Ou TT; Tsai WC; Chen CJ; Chang JG; Yen JH; Wang WS; Lin CH; Tsai JJ; Liu HW 

Address 

Department of Internal Medicine, Chung-Ho Memorial Hospital, Kaohsiung, Republic of China. 

Source 

Kao Hsiung I Hsueh Ko Hsueh Tsa Chih, 14(10):599-606 1998 Oct 

Abstract 

Overproduction of interleukin-10 (IL-10) may play an important role in the development of systemic lupus erythematosus (SLE) or lupus nephritis. There is also a polymorphic dinucleotide repeat in the human IL-10 promoter region (IL-10PR). Our aim was to study whether or not the IL-10PR alleles contributed to the susceptibility to SLE or lupus nephritis. One hundred SLE patients and 103 healthy controls were studied for IL-10PR by PCR and electrophoretic analysis. The distribution of IL-10PR alleles, genotypes and the sum of both alleles (SBA) from different groups or subgroups were analyzed. SLE patients showed no difference in the distribution of IL-10PR alleles, genotypes and SBA, as compared to healthy controls. Lupus nephritis patients (N = 49) also showed no difference in IL-10PR alleles, genotypes and SBA, as compared to SLE patients without nephritis (N = 51). Of 49 lupus nephritis patients, ten developed end-stage renal disease (ESRD) and four of them were found to suffer from rapid progressive renal failure (RPRF). Patients with RPRF presented much smaller SBA than other ESRD patients (p = 0.005). Lupus nephritis patients carrying small SBA (< 18) suffered from a higher prevalence of RPRF than lupus nephritis patients without small SBA (50% V.S. 0%, p < 0.001, relative risk 82). Our data provide the first evidence of a strong association between IL-10PR and severe progression of lupus nephritis in human patients. In the future, a prospective genetic analysis of IL-10PR for patients with lupus nephritis is recommended. It might be helpful for physicians to identify the lupus nephritis subgroup with a high risk of developing RPRF early, because this might lead to a better therapy and prognosis for these patients. 

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55.) Mucocutaneous disease in Arabs with systemic lupus erythematosus: clinical expression and relevance to autoantibodies. 

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Author 

Al-Attia HM; Al Ahmed YH 

Address 

Department of Internal Medicine in Mafraq Hospital, Abu Dhabi, United Arab Emirates. 

Source 

Lupus, 7(8):535-9 1998 

Abstract 

Both criterial and non-criterial mucocutaneous manifestations of 42 Arabs with systemic lupus erythematosus are reviewed. Photosensitivity occurred in 40.5%, malar rash in 35.75% and oral ulcers in 26% of patients. Subcutaneous nodules and subcutaneous lupus erythematosus (SCLE) were not seen, and there were few cases of discoid rash (DLE), Raynaud's phenomenon, livedo reticularis and SLE-related sicca and anticardiolipin syndromes. In the clinical relevance of autoantibodies in these patients, there was a significant association between anti-Sm antibodies and oral ulcers (P= 0.033) and, interestingly, between anti-cardiolipin (aCL) antibodies and lack of photosensitivity (P = 0.014). The report also reviews previously presented data on mucocutaneous LE in Arab and non-Arab patients and emphasises the presence of intra- and inter-racial variations of SLE expression including the clinical relevance to autoantibodies. 

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56.) Renal transplantation in systemic lupus erythematosus. A case control study of 45 patients. 

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Author 

Azevedo LS; Rom~ao JE Jr; Malheiros D; Saldanha LB; Ianhez LE; Sabbaga E 

Address 

Renal Transplantation Unit, University of S~ao Paulo Medical School, SP, Brazil. 

Source 

Nephrol Dial Transplant, 13(11):2894-8 1998 Nov 

Abstract 

BACKGROUND: Outcome and the issue of recurrence of disease in systemic lupus erythematosus (SLE) renal transplant recipients is still a matter of controversy. There is a lack of comparative studies with non-SLE patients. The aim of this paper is to compare renal transplantation in lupus patients with a similar matched non-SLE group. METHODS: Forty-five patients with systemic lupus erythematosus subjected to 48 kidney transplants were studied. For comparative purposes, a case-control population was selected, matched for gender, race, type of donor, age, and time of transplantation. Patients with non-glomerulonephritis diseases were excluded. RESULTS: No differences in acute episodes of rejection, causes of kidney loss or patient death were observed. General as well as infectious complications were similar. Pregnancy rates and outcomes were similar with no deleterious effect on patients or grafts. Actuarial 1- and 5-year patient survivals (97.7 and 91.1% for SLE and 95.4 and 87% for controls, respectively) and graft survivals (93.1 and 80.7% for SLE and 88.8 and 70.2% for controls, respectively) were similar. Long-term renal function expressed by serum creatinine was the same. No differences in immunosuppressive drug (azathioprine, prednisone, and cyclosporin) requirements were found. Clinical SLE recurrence was suspected only once (a patient with thrombocytopenia, hypocomplementaemia with low complement levels and positive antiplatelet antibodies). Two SLE patients showed mesangial proliferative glomerulonephritis compatible with recurrence. Both grafts were lost. Two further patients showed membranous glomerulonephritis with an immunofluorescence pattern compatible with recurrence. A fifth patient had necrotizing arteritis which recovered after treatment with cyclophosphamide and another patient showed focal and segmental glomerulosclerosis. Histology of biopsies from five patients in the control group showed signs compatible with recurrence of focal and segmental glomerulosclerosis and membranous glomerulonephritis. There was a wide variation in serum levels of antinuclear antibodies. A wide variation in complement levels was also observed, but with a tendency towards low C4 levels. CONCLUSIONS: The safety of renal transplantation in SLE patients is equivalent to a matched case-control group with a similar rate of recurrence of disease. 

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57.) Salmonella septic arthritis in systemic lupus erythematosus and other systemic diseases. 

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Author 

Chen JY; Luo SF; Wu YJ; Wang CM; Ho HH 

Address 

Division of Allergy, Immunology and Rheumatology, Chang Gung Memorial Hospital, Tao-Yuan, Taiwan, Republic of China. 

Source 

Clin Rheumatol, 17(4):282-7 1998 

Abstract 

Salmonella infection is an important problem in immunocompromised patients. The synovium is a particular metastatic focus of Salmonella infection and can result in many disabilities of life. Systemic lupus erythematosus (SLE) patients were highly susceptible to Salmonella infection. In the past 6 years, 41 patients with Salmonella septic arthritis have been treated in our hospital. Eleven patients had an underlying systemic disease of SLE which presented with a distinctive clinical course. Alcoholic liver disease (six cases) was another common underlying systemic disease. The most frequent predisposing articular factor was avascular necrosis (16 cases). The hip joint was the most commonly involved site. Salmonella group B was the most common serotype (30/41). Seventy-three per cent (8/11) of the SLE group had involvement of two or more joints compared with only three out of 30 patients in the non-SLE group. The sex differentiation shows a predominance of young females (10/11) in the SLE group and middle-aged males in the non-SLE group. Moreover, in the SLE group, all 11 patients shared the risk of lupus nephritis and steroid use. Ten patients had Salmonella group B bacteraemia and five had urinary tract infections simultaneously. In the non-SLE group, there were 10 patients with a history of steroid use, three with antecedent enteritis, 12 with bacteraemia, and three with necrotising fasciitis. Seven patients in each of the groups had a recurrent course. However, three patients in the non-SLE group had died during the episode of septic arthritis. 

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58.) Neuropsychiatric systemic lupus erythematosus and the syndrome of inappropriate secretion of antidiuretic hormone: a case report with very late onset systemic lupus erythematosus. 

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Author 

Mirsattari SM; Power C; Fine A; McGinn GS; Ludwick S; Canvin JM 

Address 

Department of Internal Medicine, University of Manitoba Health Sciences Centre, Winnipeg, Canada. 

Source 

Br J Rheumatol, 37(10):1132-4 1998 Oct 

Abstract 

The syndrome of inappropriate secretion of antidiuretic hormone (SIADH) associated with neuropsychiatric lupus (NP-SLE) is rare. We report a case of SIADH associated with the new onset of SLE in an 88-yr-old female. The unique features of this case include the extreme age of onset of SLE presenting with neuropsychiatric manifestations and positive antiribosomal P antibody titres. Both the NP manifestations of SLE and SIADH were highly correlated with the SLE disease activity. This case illustrates a novel presentation of NP-SLE with SIADH which may develop due to antibody-mediated hypothalamic dysfunction. 

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59.) Myocardial infarction in patients with systemic lupus erythematosus with normal findings from coronary arteriography and without coronary vasculitis--case reports. 

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Author 

Rangel A; Lavalle C; Ch´avez E; Jim´enez M; Acosta JL; Badu´i E; Albarr´an H 

Address 

Departamento de Hemodinamia, Hospital De Especialidades, Centro Medico La Raza, IMSS, Mexico City, Mexico. 

Source 

Angiology, 50(3):245-53 1999 Mar 

Abstract 

The authors present the cases of two young patients, a man and a woman, who presented with myocardial infarction, in the absence of ischemic heart disease or stenosis of the coronary arteries. The woman was known to have systemic lupus erythematosus (SLE) for the past 3 years (the immunoglobulin M [IgM] anticardiolipins antibodies were positive), without a history of coronary risk factors. Suddenly she presented with acute chest pain on rest that lasted 4 hours and culminated in anterior wall myocardial infarction. She was admitted to the coronary care unit, where no thrombolysis was given. She did not have echocardiographic evidence of Libman-Sacks endocarditis, but myocardial infarction was evident at the electrocardiogram (ECG). The young man had SLE (the IgM anticardiolipins were absent, but he was positive for lupus anticoagulant antibodies), he was hyperlipidemic, was a moderate smoker and moderately obese, and had no history of ischemic heart disease. He suddenly presented with an acute myocardial infarction documented by ECG, enzymes, and gammagraphy. In both patients, coronary angiography findings were normal and myocardial biopsy did not show evidence of arteritis. The relevance of these cases is the rare association of ischemic heart disease in SLE, with normal coronary arteries and without evidence of arteritis or verrucous endocarditis. 

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60.) [Is autoantibody determination in patients with systemic lupus erythematosus useful? Anti-C1q-autoantibody as an example] 

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Author 

Trendelenburg M; Schifferli JA 

Address 

Medizinische Klinik B, Universit¨atsspital Basel. 

Source 

Schweiz Rundsch Med Prax, 87(51-52):1811-3 1998 Dec 24 

Abstract 

Many autoantibodies have been described in patients with systemic lupus erythematosus. However, besides antibodies to dsDNA, the majority of them has not been shown to help the clinician. It is interesting to note that the recently described autoantibodies to C1q strongly correlate with the occurrence or worsening of a preexisting lupus nephritis. 

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61.) Association between prolactin and disease activity in systemic lupus erythematosus. Influence of statistical power. 

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Author 

Blanco-Favela F; Quintal-Alvarez G; Lea~nos-Miranda A 

Address 

Pediatric Hospital, National Medical Center Siglo XXI, Instituto Mexicano del Seguro Social, M´exico, DF. 

Source 

J Rheumatol, 26(1):55-9 1999 Jan 

Abstract 

OBJECTIVE: To analyze the statistical power of studies in the medical literature on the relationship between prolactin (PRL) and systemic lupus erythematosus (SLE) activity. METHODS: Published studies that were identified through MEDLINE search, as well as references from these articles, were reviewed. RESULTS: We identified 5 articles that sought to establish a relationship between PRL and SLE activity. In 4 of them, the frequency of hyperprolactinemia in SLE (>20 ng/ml) was 2.2-47.2%, and in one article, there was a relationship between PRL and SLE activity. A power analysis of individual studies could be carried out in only 2 of the 5; there were no significant effects; the 2 articles cited differences in the frequency of hyperprolactinemia in patients with and without lupus activity (1.6 and 12.3%, respectively), but because of a low power of the studies (> or =30.8%), it could not be determined whether the differences in the frequency of hyperprolactinemia were significant. On the other hand, joint analysis of 3 articles showed a significant association between hyperprolactinemia and lupus activity. CONCLUSION: Published clinical results concerning the relationship between PRL and Jupus activity are contradictory, due in part to the statistical power of the studies. Our analysis of these studies showed that PRL is related to lupus activity, without establishing a formal causal relationship. 

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62.) Correlation of 9G4 idiotope with disease activity in patients with systemic lupus erythematosus. 

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Author 

Isenberg DA; McClure C; Farewell V; Spellerberg M; Williams W; Cambridge G; Stevenson F 

Address 

Centre For Rheumatology/Bloomsbury Rheumatology Unit, University College London. 

Source 

Ann Rheum Dis, 57(9):566-70 1998 Sep 

Abstract 

OBJECTIVE: To compare the levels of the 9G4 idiotope (9G4 Id) in systemic lupus erythematosus (SLE) patients with a detailed disease activity index, the British Isles Lupus Assessment Group (BILAG) index, and serological parameters of disease activity by ds DNA antibody levels and serum C3 concentrations. METHODS: In a cross sectional analysis serum samples from 190 patients with SLE were studied and a further 55 serial bleeds from 14 patients. An enzyme linked immunosorbent assay was used to measure the 9G4 Id, and anti dsDNA and antimyeloperoxidase (MPO) antibodies. The C3 levels were measured by laser nephelometer. RESULTS: Seventy six of 190 (40%) of the patients tested had raised 9G4 Id levels. In the cross sectional study 9G4 Id levels were found to correlate with disease activity in the BILAG cardiovascular/respiratory renal, and haematological systems and with global BILAG score (p < 0.01). In the serial bleeds 9G4 Id levels correlated with anti-dsDNA antibody and C3 levels, but not with anti-MPO antibodies. No correlations were found with treatment. In six cases the 9G4 Id levels correlated well with global BILAG scores and dsDNA antibody levels. In four cases the BILAG global and 9G4 Id levels alone correlated well. CONCLUSIONS: Raised levels of the 9G4 Id are present in a substantial proportion of serum samples from patients with lupus, correlate with various aspects of disease activity in SLE. The Id is detectable on anti-dsDNA antibodies, though it must also be present on other immunoglobulins whose specificities remain unknown. 

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63.) Systemic lupus erythematosus: perinatal and neonatal implications. 

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Author 

Classen SR; Paulson PR; Zacharias SR 

Address 

Denver Health Medical Center, CO 80204, USA. 

Source 

J Obstet Gynecol Neonatal Nurs, 27(5):493-500 1998 Sep-Oct 

Abstract 

Systemic lupus erythematosus (SLE) is a chronic autoimmune disorder that can affect almost all organ systems in the body. It is most common in women of childbearing age and may cause multiple peripartum complications. This article reviews the pathophysiology of SLE and the effects of SLE on fertility and pregnancy. The complexities of managing a pregnant patient with SLE are reviewed, and the importance of interdisciplinary collaboration discussed, as well as the effects of SLE on the fetus and a review of neonatal lupus erythematosus. Finally, a case report of a pregnant patient with SLE with challenging clinical management issues is presented. 

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64.) Autologous peripheral blood stem and progenitor (CD34+) cell transplantation for systemic lupus erythematosus complicated by Evans syndrome. 

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Author 

Musso M; Porretto F; Crescimanno A; Bondi F; Polizzi V; Scalone R; Mariani G 

Address 

Division of Haematology, University of Palermo, Italy. 

Source 

Lupus, 7(7):492-4 1998 

Abstract 

Immunoablation followed by allogeneic stem cell (SC) transplantation has been shown to be capable of curing a large spectrum of experimental autoimmune disorders, hereditary and/or induced. Superimposable results, albeit with some exceptions, have been obtained in human patients affected by coincidental autoimmune and blood diseases. However, both because of encouragine experimental results and of the procedure's greater safety, autologous SC are being increasingly utilized worldwide. Case reports are being collected in the registry of the European Group for Blood and Marrow Transplantation (EBMT)/European League against Rheumatism (EULAR) Autoimmune Disease Stem Cell Project. Among the severe autoimmune diseases (SADs), which are the target of autologous transplantation, severe refractory systemic lupus erythematosus (SLE) is a condition which may benefit from this procedure. We report here the case of a 19 year old female patient with a six year history of SLE with secondary antiphospholipid syndrome (APS), who later developed refractory Evans syndrome. She was transplanted with autologous mobilized CD34+ SC and progenitor cells after conditioning with cyclosphosphamide, anti-T lymphocyte globulin and prednisone. Eight months after transplant, the patient is alive and well, with normal blood counts and persistent low-titre direct antiglobulin (DAT, Coombs) and anti-nuclear antibody (ANA) tests. Anti-double stranded DNA antibody (Anti-dsDNA), lupus anticoagulant tests and anti-cardiolipin antibody (ACA) test are negative. 

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65.) [Evolutive aspects of systemic lupus erythematosus in Dakar. Apropos of 30 cases] 

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Author 

Ka MM; Diouf B; Mbengue M; Kane A; Wade B; Diallo S; Diop TM 

Address 

Clinique m´edicale, CHU A. Le Dantec, Dakar, S´en´egal. mmka@hdantec.refer.sn 

Source 

Bull Soc Pathol Exot, 91(4):306-8 1998 

Abstract 

To determine the characteristics of evolution of systemic lupus erythematosus (SLE), the authors studied 30 cases retrospectively. All were black women aged from 16 to 73 years (with a mean of 30 years) at the time of diagnosis. Dermatological manifestations consisting in discoid lupus or alopecia inaugurated the disease in 12 cases, joint symptoms in 10 cases. Polyarthritis was the most common inaugural manifestation, followed by discoid lupus. Corticosteroids therapy alone or associated to chloroquine or immunosuppressor led to good results; 88% of patients who received treatment had good outcomes in the first 5 months after diagnosis. After this time lapse, 6 cases of complications related to the corticosteroids therapy occurred. After one year, 5 patients presented one or more flare-ups and had to be re-hospitalized; 8 others were lost to the follow-up. The overall mortality rate was 27% (8 cases out of 30). Causes of death were first renal failure (3/8) followed by infectious complications (2/8). The management of SLE could be improved by a close follow-up and providing the patients and their family with adequate information. 

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66.) Autoantibodies in systemic lupus erythematosus. 

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Author 

Cabral AR; Alarc´on-Segovia D 

Address 

Department of Immunology and Rheumatology, Instituto Nacional de la Nutricion Salvador-Zubiran, Mexico DF, Mexico. 

Source 

Curr Opin Rheumatol, 10(5):409-16 1998 Sep 

Abstract 

Cationic germ line gene-encoded anti-DNA antibodies appear to cause inflammatory lesions via deposition and in situ formation of immune complexes, but also perhaps through apoptosis of glomerular mesangial cells. Somatic mutation is not critical for the expression of the electrical net charge of anti-DNA. In one transgenic mouse model, the nephrogenicity of anti-DNA was dependent on the expression of interleukin alpha by epidermal cells. Anti-P autoantibodies are present in the serum of healthy children but are masked by IgG antibodies. Some anti-P antibodies appear to be a subset of antilymphocyte autoantibodies. It was confirmed that anti-Ro/SS-A antibodies react with structurally unrelated conformational epitopes. The combined results of immunofluorescence and enzyme-linked immunosorbent assay in the detection of antineutrophil cytoplasmic antibody has a 99.5% specificity for vasculitis among patients with connective tissue diseases. Antinucleosome antibodies are highly prevalent in patients with systemic lupus erythematosus and show an inverse correlation with nucleosome plasma levels. Transfected T-cell receptor alpha chains specific for nucleosomal autoepitopes from a Th clone that accelerates lupus nephritis, recognized the nucleosomal epitopes presented by antigen presenting cell-bearing 1-A molecules, as well as human DR molecules, via the classical major histocompatibility complex class II groove. IgG antibodies against (beta 2 -glycoprotein (GP)-1 are significantly associated with thrombosis in patients with antiphospholipid syndrome, with a specificity and sensitivity that ranges from 85% to 98% and 32% to 54%, respectively. The lupus anticoagulant activity, or the lack of it, of anti-beta 2-glycoprotein-1 appears to reside on the epitope specificity. Beta 2-glycoprotein-1 binds to apoptotic cells; in turn, anti-beta 2-glycoprotein-1 facilitate apoptotic cell clearance by macrophages. The recently described anti-A2/RA33 autoantibody appears to recognize an epitope capable of distinguishing patients with lupus or with rheumatoid arthritis from those with mixed connective tissue disease. 

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67.) The genetics of human systemic lupus erythematosus. 

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Author 

Harley JB; Moser KL; Gaffney PM; Behrens TW 

Address 

Oklahoma City US Department of Veterans Affairs Medical Center University of Oklahoma Health Sciences Center Oklahoma Medical Research Foundation 825 N.E. 13th Street Oklahoma City Oklahoma 73104 USA. john-harley@omrf.ouhsc.edu 

Source 

Curr Opin Immunol, 10(6):690-6 1998 Dec 

Abstract 

Major advances in understanding the genetic foundation of systemic lupus erythematosus are in the offing. Genetic association studies suggest multiple effects that include those encoded by the HLA region, the genes for Fcgamma receptors and other genes such as that for the mannose-binding protein. Genome scan studies suggest many (at least twelve) genetic linkages with lupus. Identifying the genes linked with lupus is likely to require many years of concerted effort, as well as the availability and evaluation of much larger pedigree collections. 

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68.) Exacerbation of systemic lupus erythematosus related to cytomegalovirus infection. 

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Author 

Hayashi T; Lee S; Ogasawara H; Sekigawa I; Iida N; Tomino Y; Hashimoto H; Hirose S 

Address 

Department of Medicine, Jutendo University Izu-Nagaoka Hospital, Shizuoka, Japan. 

Source 

Lupus, 7(8):561-4 1998 

Abstract 

We report two patients with systemic lupus erythematosus (SLE) in whom cytomegalovirus (CMV) infection may have played a significant role in the exacerbation or onset of symptoms. The first patient had thrombocytopenia and the second had proteinuria. CMV infection was observed in both patients when their symptoms developed. 

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69.) Visual disturbance by lymphocytic hypophysitis in a non-pregnant woman with systemic lupus erythematosus. 

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Author 

Katano H; Umemura A; Kamiya K; Kanai H; Yamada K 

Address 

Department of Neurosurgery, Nagoya City University Medical School, Nagoya, Japan. 

Source 

Lupus, 7(8):554-6 1998 

Abstract 

The authors present the case of a patient with systemic lupus erythematosus who developed visual disturbance and amenorrhea. Though the clinical and radiological findings resembled those of pituitary adenoma, the patient was finally diagnosed as having lymphocytic hypophysitis after the operation. We briefly describe this relatively rare entity in relation to its autoimmune pathogenesis. 

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70.) Pulmonary involvement in juvenile systemic lupus erythematosus: a study on lung function in patients asymptomatic for respiratory disease. 

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Author 

Trapani S; Camiciottoli G; Ermini M; Castellani W; Falcini F 

Address 

Department of Pediatrics, University of Florence, Italy. 

Source 

Lupus, 7(8):545-50 1998 

Abstract 

Pleuro-pulmonary involvement has been well recognized in adults affected with systemic lupus erythematosus (SLE), but few studies have been carried out in children. A longitudinal study on a group of 15 children affected with juvenile SLE (JSLE), asymptomatic for lung disease, was performed, and the prevalence and the features of respiratory function alterations, over a period of 12 months, were analysed. Moreover, a possible correlation between any pulmonary function test (PFT) and disease duration, disease activity, visceral involvement and immunological pattern was evaluated. At baseline, a significant functional lung impairment was present in 40% of patients, with a significantly reduced FVC, VA and DLCO in 26% of them; in 60% of patients at 6 months and in 33% of patients at 12 months. At 6 and 12 months, our data did not show any significant modification in PFTs and the restrictive pattern, observed at baseline, remained unchanged. No correlation between altered PFTs and disease duration, activity and/or immunological findings was found. At baseline, the presence of neurological involvement was the only extra-pulmonary feature correlated to reduced FVC. 

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71.) Genome scan of human systemic lupus erythematosus: evidence for linkage on chromosome 1q in African-American pedigrees. 

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Author 

Moser KL; Neas BR; Salmon JE; Yu H; Gray-McGuire C; Asundi N; Bruner GR; Fox J; Kelly J; Henshall S; Bacino D; Dietz M; Hogue R; Koelsch G; Nightingale L; Shaver T; Abdou NI; Albert DA; Carson C; Petri M; Treadwell EL; James JA; Harley JB 

Address 

Arthritis and Immunology Program, Oklahoma Medical Research Foundation, Oklahoma City, OK 73104, USA. 

Source 

Proc Natl Acad Sci U S A, 95(25):14869-74 1998 Dec 8 

Abstract 

Systemic lupus erythematosus (SLE) is an autoimmune disorder characterized by production of autoantibodies against intracellular antigens including DNA, ribosomal P, Ro (SS-A), La (SS-B), and the spliceosome. Etiology is suspected to involve genetic and environmental factors. Evidence of genetic involvement includes: associations with HLA-DR3, HLA-DR2, Fcgamma receptors (FcgammaR) IIA and IIIA, and hereditary complement component deficiencies, as well as familial aggregation, monozygotic twin concordance >20%, lambdas > 10, purported linkage at 1q41-42, and inbred mouse strains that consistently develop lupus. We have completed a genome scan in 94 extended multiplex pedigrees by using model-based linkage analysis. Potential [log10 of the odds for linkage (lod) > 2.0] SLE loci have been identified at chromosomes 1q41, 1q23, and 11q14-23 in African-Americans; 14q11, 4p15, 11q25, 2q32, 19q13, 6q26-27, and 12p12-11 in European-Americans; and 1q23, 13q32, 20q13, and 1q31 in all pedigrees combined. An effect for the FcgammaRIIA candidate polymorphism) at 1q23 (lod = 3.37 in African-Americans) is syntenic with linkage in a murine model of lupus. Sib-pair and multipoint nonparametric analyses also support linkage (P < 0.05) at nine loci detected by using two-point lod score analysis (lod > 2.0). Our results are consistent with the presumed complexity of genetic susceptibility to SLE and illustrate racial origin is likely to influence the specific nature of these genetic effects. 

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72.) Cutaneous manifestations of childhood systemic lupus erythematosus. 

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Author 

Wananukul S; Watana D; Pongprasit P 

Address 

Department of Pediatrics, Chulalongkorn University, Bangkok, Thailand. 

Source 

Pediatr Dermatol, 15(5):342-6 1998 Sep-Oct 

Abstract 

We assessed the mucocutaneous signs in 57 children with classical systemic lupus erythematosus seen during a 6 year period. The female:male ratio was 4.2:1. Ages ranged from 4 to 15 years (mean 11.9 years) at the time of diagnosis. Cutaneous manifestations (77%) were the second most common finding, next to renal involvement (84%). The skin changes noted were malar rash (74%), oral ulcer (46%), vasculitis (42%), photosensitivity (40%), alopecia (32%), and discoid lupus erythematosus (LE) (19%). All 11 discoid LE patients were girls. Periungual erythema, Raynaud's phenomenon, periungual gangrene, nail involvement, and subacute LE were rare. Antinuclear antibody reaction was positive in 93% and anti-dsDNA was positive in 46%. Eight patients died, six from severe infection and two from renal failure. 

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73.) Gender differences in autoimmune diseases: estrogen increases calcineurin expression in systemic lupus erythematosus. 

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Author 

Rider V; Foster RT; Evans M; Suenaga R; Abdou NI 

Address 

School of Biological Sciences, University of Missouri-Kansas City, Kansas City, Missouri, 64110, USA. 

Source 

Clin Immunol Immunopathol, 89(2):171-80 1998 Nov 

Abstract 

Systemic lupus erythematosus (SLE) predominantly affects women (9:1 compared to men) of childbearing age and often decreases its intensity in postmenopausal women, suggesting that sex hormones play a role in its pathogenesis. Comparison of steady-state levels of calcineurin mRNA using RNase protection assays revealed increased calcineurin expression in response to estradiol in cultured T cells from nine female lupus patients. Calcineurin mRNA levels did not increase significantly in T cells from eight age-matched normal control female volunteers. Estrogen-dependent calcineurin mRNA increased in a dose-dependent fashion, while progesterone and dexamethasone did not increase calcineurin mRNA in patient cells. Lupus T cell calcineurin mRNA increased in response to estradiol at 6 h but not at 3 h. Calcineurin phosphatase activity increased in lupus T cell extracts after incubation of cells with estradiol, while phosphatase activity in normal T cells was unaffected by estrogen. Calcineurin expression in T cells from patients with vasculitis and rheumatoid arthritis taking medications similar to those taken by the lupus patients was unaffected by estradiol. This study provides the first evidence for a molecular marker of estrogen action in lupus patients and suggests that estrogen-dependent changes in lupus T cell calcineurin could alter proinflammatory cytokine gene regulation and T-B cell interactions. 

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74.) Anti-beta2-glycoprotein I, anti-prothrombin and anticardiolipin antibodies in a longitudinal study of patients with systemic lupus erythematosus and the antiphospholipid syndrome. 

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Author 

Inan¸c M; Donohoe S; Ravirajan CT; Radway-Bright EL; Mackie I; Machin S; Isenberg DA 

Address 

Department of Medicine, University College London. 

Source 

Br J Rheumatol, 37(10):1089-94 1998 Oct 

Abstract 

OBJECTIVE: To determine anti-beta2 glycoprotein-I (anti-beta2GPI) and anti-prothrombin (anti-ProT) antibody levels, and the IgG subclass distribution of anti-beta2GPI antibodies, in serial samples from patients with systemic lupus erythematosus (SLE) and antiphospholipid syndrome (APS) having initial or recurrent thrombotic/neurological (T/N) events during the study period. To investigate the correlations between these antibodies and beta2GPI antigen, anticardiolipin antibody (aCL), anti-double-stranded (ds) DNA, C3 levels and disease activity. METHODS: Fifty serum samples were identified from seven patients with SLE who had had T/N events during the follow-up from a cohort under long-term follow-up. IgG anti-beta2GPI, anti-ProT, aCL, IgG subclasses of anti-beta2GPI and beta2GPI antigen levels were determined by ELISA. Corresponding disease activity [British Isles Lupus Assessment Group (BILAG)], anti-dsDNA and C3 levels were compared. RESULTS: IgG anti-beta2GPI antibody levels were elevated in six of the patients before and after the T/N events with less marked fluctuations than aCL antibody levels. The predominant subclass of anti-beta2GPI antibodies was IgG2 before and after the T/N events. IgG anti-ProT antibodies were negative in all cases. There was a significant but weak correlation between anti-beta2GPI and aCL antibodies. No correlation was found between disease activity and IgG anti-beta2GPI antibody and beta2GPI antigen levels. There were fluctuations in beta2GPI antigen levels and a trend to increase after T/N events was observed in some patients. CONCLUSION: Most of the patients with a T/N event during the study period had IgG anti-beta2GPI, but not IgG anti-ProT antibodies. Many IgG aCL-negative samples were found to have IgG anti-beta2GPI activity during the follow-up period. The predominant subclass of IgG anti-beta2GPI was IgG2, which may have importance in the pathogenesis of APS. beta2GPI antigen levels were found to be increased in some patients with SLE after T/N events. IgG anti-beta2GPI antibodies may be used as an adjunctive marker of future T/N events in patients with SLE and APS with aCL antibodies and lupus anticoagulant. 

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75.) Identification and characterization of a calreticulin-binding nuclear protein as histone (H1), an autoantigen in systemic lupus erythematosus. 

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Author 

Treves S; Bajocchi G; Zorzato F; Govoni M; Trotta F 

Address 

Department of Experimental and Diagnostic Medicine, University of Ferrara, Italy. zor@ifeuniv.unife.it 

Source 

Lupus, 7(7):479-87 1998 

Abstract 

Our objective was to identify nuclear calreticulin-binding protein(s) and investigate whether there is a correlation between presence of autoantibodies against calreticulin and calreticulin-binding protein(s) in the sera of patients suffering from systemic lupus erythematosus (SLE). The ligand overlay procedure using digoxigenin-labelled calreticulin was used to identify a calreticulin-binding protein in the nuclear fraction of bovine brain. Fractionation of the nuclear components was used to localize the major positive calreticulin-binding protein. The protein was partially purified using hydroxylapatitie chromatography and subjected to NH2-amino acid sequence analysis. Immunoblots using the sera of SLE patients were then carried out on calreticulin and the calreticulin-binding protein. The calreticulin-binding protein present in the nucleoplasm was identified as histone H1. Approximately 62% (26/42) patients with SLE had IgG antibodies directed against H1 whereas the sera of healthy individuals did not react with the antigen; 36% of patients with SLE had both anti-calreticulin and anti-histone H1 antibodies. Phosphorylation of the latter protein did not alter its immunoreactivity. These findings demonstrate that the concomitant presence of autoantibodies directed against both calreticulin and histone H1 occurs frequently in patients with SLE and may help shed some light on the mechanisms which bring about the autoimmune response. 

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76.) Systemic lupus erythematosus in Kuwait--hospital based study. 

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Author 

Al-Jarallah K; Al-Awadi A; Siddiqui H; Al-Salim I; Shehab D; Umamaheswaran I; Gaurer S; Al-Saied K; Kumar R; Malaviya AN 

Address 

Department of Medicine, Faculty of Medicine, Kuwait University, Mubarak Al-Kabeer Hospital, Safat. 

Source 

Lupus, 7(7):434-8 1998 

Abstract 

The present study describes the clinical characteristics of patients with systemic lupus erythematosus (SLE), from the rheumatology service of the two main teaching hospitals in Kuwait. It was a retrospective-cum-prospective clinical study of 108 SLE patients. There were 98 females and 10 males, with a median age of 31.5y. Kuwaitis constituted 69%, while 31% were expatriates. The mean disease duration was 62 months. The main clinical features were: musculoskeletal involvement (87%), photosensitivity (48%), malar rash (43%), discoid lesions (10%), oral ulcers (33%), vasculitic skin lesions (10%), haematological features (53%), constitutional symptoms (51.4%), neuropsychiatric manifestations (23%), renal involvement (37%), serositis (29%), clinical manifestations of antiphospholipid syndrome (21%), cardiac involvement (10%) and pulmonary manifestations (19%). In conclusion, the clinical features of SLE in Kuwait were similar to most major studies from developed countries. Main differences included prominent haematological and mucocutaneous manifestations and possibly a low prevalence of anti-Sm antibodies. Whether these differences are due to the environment or genetic factors, remains to be studied. 

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77.) Use of intravenous immunoglobulin therapy in pregnancy in systemic lupus erythematosus and antiphospholipid antibody syndrome. 

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Author 

Gordon C; Kilby MD 

Address 

Department of Rheumatology, University of Birmingham, UK. p.c.gordon@bham.ac.uk 

Source 

Lupus, 7(7):429-33 1998 

Abstract 

Systemic lupus erythematosus and antiphospholipid antibody syndrome are associated with an increased risk of intrauterine growth restriction, miscarriage, stillbirth and premature delivery. Recent advances in therapy during pregnancy have improved the outcome but there is still significant fetal and maternal morbidity and mortality. Treatment of patients failing conventional therapy during the second half of pregnancy is difficult and may be complicated by the development of preeclampsia. The addition of intravenous immunoglobulin therapy offers a low risk strategy for reducing autoantibody mediated disease and improving placental function in severely compromised, growth restricted pregnancies. 

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78.) Relationship between neurometabolite derangement and neurocognitive dysfunction in systemic lupus erythematosus. 

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Author 

Brooks WM; Jung RE; Ford CC; Greinel EJ; Sibbitt WL Jr 

Address 

Center for Non-Invasive Diagnosis and the Department of Neurosciences, The University of New Mexico Health Sciences Center, Albuquerque 87131-5021, USA. 

Source 

J Rheumatol, 26(1):81-5 1999 Jan 

Abstract 

OBJECTIVE: To determine the relationship between neurochemical markers of brain injury and brain dysfunction associated with systemic lupus erythematosus (SLE). METHODS: Patients with SLE (n = 12) were studied using magnetic resonance spectroscopic imaging at 1.5 Tesla to determine neurochemistry and a neurocognitive testing battery to determine brain dysfunction. N-acetylaspartate (NAA), creatine (Cre), and choline (Cho) concentrations were measured in white (WM) and gray (GM) matter and expressed as the ratios NAA/Cho, NAA/Cre, and Cho/Cre. Neurocognitive testing results were expressed as a composite z score. Disease activity was quantified by SLE Disease Activity Index (SLEDAI) and disease injury by Systemic Lupus International Collaborating Clinics (SLICC)/American College of Rheumatology Damage Index. RESULTS: Neurochemical measures of brain injury were correlated with neurocognitive testing z scores: NAA/Cho in WM (r = 0.77, p = 0.003) and GM (r = 0.67, p = 0.017); WM Cho/Cre also correlated with total z score (r = -0.74, p = 0.006). Neurometabolite ratios and SLICC were correlated: GM NAA/Cho (r = -0.70, p = 0.011 ) and NAA/Cre (r = -0.71, p = 0.01) and WM Cho/Cre (r = 0.66, p = 0.02). Correlations between neurometabolite ratios and SLEDAI did not reach significance. CONCLUSION: Brain function is closely correlated with brain injury assessed noninvasively by proton magnetic resonance spectroscopy. This important finding further supports the use of magnetic resonance spectroscopy to evaluate brain injury in SLE. 

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79.) Mutations in T cell receptor zeta chain mRNA of peripheral T cells from systemic lupus erythematosus patients. 

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Author 

Tsuzaka K; Takeuchi T; Onoda N; Pang M; Abe T 

Address 

Second Department of Internal Medicine, Saitama Medical Center, Saitama Medical School, 1981 Kamoda, Kawagoe, Saitama 350, Japan. 

Source 

J Autoimmun, 11(5):381-5 1998 Oct 

Abstract 

Systemic lupus erythematosus (SLE) is a systemic autoimmune disease of unknown aetiology. Although it has been reported that T cells might be responsible for the pathogenesis of SLE, it remains unclear whether immune aberrations of SLE T cells are the primary event in this pathological process. We have recently reported that tyrosine phosphorylation and expression of the T cell receptor zeta chain (TCR zeta) was significantly decreased in SLE T cells and that two SLE patients exhibited a 36 bp, exon 7 deletion of the TCR zeta mRNA. To investigate further common mutations in TCR zeta mRNA among SLE patients, mRNA was isolated from the peripheral blood T cells of two normal controls, two systemic sclerosis (SSc) patients, and eight SLE patients. TCR zeta cDNA was amplified by RT-PCR. Five out of the eight SLE patients exhibited abnormal migration patterns of the TCR zeta cDNA in PCR single stranded conformational polymorphism analysis. PCR products were ligated into pUC18 and five clones obtained were sequenced. Analysis of the nucleotide sequences revealed that all of the five pUC18 clones from the normal controls and SSc patients had the normal nucleotide sequence, whereas all eight SLE patients had mutations in TCR zeta cDNA accompanied by predicted amino acid substitutions. Mutations found in six of these patients corresponded to those of the third immunoreceptor tyrosine-based activation motif (ITAM) domain or the GTP/GDP binding site in TCR zetaThus, these mutations in TCR zeta mRNA could be responsible for the decreased expression of the TCR zeta protein in SLE T cells. 

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80.) C1q and systemic lupus erythematosus. 

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Author 

Walport MJ; Davies KA; Botto M 

Address 

Department of Medicine, Imperial College School of Medicine, London, U.K. 

Source 

Immunobiology, 199(2):265-85 1998 Aug 

Abstract 

In this chapter we review the association between SLE and C1q. In the first part of the chapter we discuss the clinical associations of C1q deficiency, and tabulate the available information in the literature relating to C1q deficiency and autoimmune disease. Other clinical associations of C1q deficiency are then considered, and we mention briefly the association between other genetically determined complement deficiencies and lupus. In the review we explore the relationship between C1q consumption and lupus and we discuss the occurrence of low molecular weight (7S) C1q in lupus, which raises the possibility that increased C1q turnover in the disease may result in unbalanced chain synthesis of the molecule. Anti-C1q antibodies are also strongly associated with severe SLE affecting the kidney, and with hypocomplementaemic urticarial vasculitis, and these associations are also examined. We address the question of how C1q deficiency may cause SLE, discussing the possibility that this may be due to abnormalities of immune complex processing, which have been well characterised in a umber of different human models. There is clear evidence that immune complex processing is abnormal in patients with hypocomplementaemia, and this is compatible with the hypothesis that ineffective immune complex clearance could cause tissue injury, and this may in turn stimulate an autoantibody response. We have also considered the possibility that C1q-C1q receptor interactions are critical in the regulation of apoptosis, and we explore the hypothesis that dysregulation of apoptosis could explain important features in the development of autoimmune disease associated with C1q deficiency. An abnormally high rate of apoptosis, or defective clearance of apoptotic cells, could promote the accumulation of abnormal cellular products that might drive an autoimmune response. Anti-C1q antibodies have been described in a number of murine models of lupus, and these are also briefly discussed. We focus on the recently developed C1q "knockout" mice, which have been developed in our laboratory. Amongst the C1q deficient mice of a mixed genetic background high titres of antinuclear antibodies were detected in approximately half the animals, and around 25% of the mice, aged eight months had evidence of a glomerulonephritis with immune deposits. Large numbers of apoptotic bodies were also present in diseased glomeruli, and this supports the hypothesis that C1q may have a critical role to play in the physiological clearance of apoptotic cells. 

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81.) A multicentre study of 513 Danish patients with systemic lupus erythematosus. I. Disease manifestations and analyses of clinical subsets. 

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Author 

Jacobsen S; Petersen J; Ullman S; Junker P; Voss A; Rasmussen JM; Tarp U; Poulsen LH; van Overeem Hansen G; Skaarup B; Hansen TM; Pødenphant J; Halberg P 

Address 

Department of Rheumatology at Copenhagen University Hospitals at Hvidovre Hospital, Hvidovre, Denmark. 

Source 

Clin Rheumatol, 17(6):468-77 1998 

Abstract 

A Danish multicentre study was undertaken of the manifestations, infections, thrombotic events, survival and predictive factors of survival in 513 Danish patients with systemic lupus erythematosus (SLE) according to the 1982 classification criteria of the American College of Rheumatology. The mean duration of follow-up was 8.2 years from diagnosis and 12.8 years from first symptom. This paper describes the most common clinical and laboratory manifestations and their relationship to sex and age at the time of onset and diagnosis. Cluster analysis revealed three clinically defined clusters at the time of disease onset. Cluster 1 (57% of patients) consisted of relatively elderly patients without nephropathy or malar rash, but with a high prevalence of discoid lesions. Cluster 2 (18%) consisted of patients with nephropathy, a third of whom also developed serositis and lymphopenia. The patients of the third cluster (25%) all had malar rash and half were photosensitive. Follow-up showed that the patients of cluster 2 developed azotaemia, large proteinuria, arterial hypertension and myositis significantly more often than did the rest of the patients, but the mortality was not increased. The risk of developing renal end-stage disease was highest in men with early-onset disease. 

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82.) Renal manifestations of concurrent systemic lupus erythematosus and HIV infection. 

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Author 

Chang BG; Markowitz GS; Seshan SV; Seigle RL; D'Agati VD 

Address 

Department of Pathology, Columbia Presbyterian Medical Center, New York, NY 10032, USA. 

Source 

Am J Kidney Dis, 33(3):441-9 1999 Mar 

Abstract 

Autoimmune phenomena are common in human immunodeficiency virus (HIV) infection, yet systemic lupus erythematosus (SLE) and HIV infection rarely are seen concurrently in the same patient. Many of the cases of combined HIV infection and SLE reported in the literature are patients with SLE before HIV infection and who did not undergo renal biopsy at a time when both processes were present. We report the clinical manifestations and renal biopsy findings in four subjects with concurrent HIV infection and SLE and compare them with the seven previously reported cases in the literature. Taken together, most patients were black (91%) and male (73%), and approximately half (55%) were children with perinatal HIV infection. These demographics differ markedly from those of idiopathic SLE, a disease that predominantly affects female adults. Renal presentations included proteinuria and hypocomplementemia, frequently with hematuria and renal insufficiency. Renal biopsy findings in 10 cases included all classes of lupus nephritis (class IIb in two cases, class III in one case, class IV in three cases, class V in three cases, class III and V in one case), two of which also displayed overlapping features of HIV-associated nephropathy (HIVAN). One case had isolated findings of HIVAN. This cohort provides a unique population in which to study interacting pathomechanisms between HIV infection and SLE. 

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83.) Glomerular thrombosis: an unusual cause of renal failure in systemic lupus erythematosus. 

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Author 

Uwonkunda MR; Cosyns JP; Devogelaer JP; Houssiau FA 

Address 

Service de Rhumatologie et d'Anatomie Pathologique, Universit´e Catholique de Louvain, Bruxelles, Belgique. 

Source 

Acta Clin Belg, 53(6):371-3 1998 Dec 

Abstract 

The authors report an unusual case of acute renal failure occurring in a patient with systemic lupus erythematosus and antiphospholipid antibodies. Kidney biopsy revealed glomerular thrombosis, in the absence of glomerulonephritis. The authors stress the clinical and biological signs that suggest the thrombotic nature of kidney failure in lupus patients. 

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84.) Coexistent minocycline-induced systemic lupus erythematosus and autoimmune hepatitis. 

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Author 

Angulo JM; Sigal LH; Espinoza LR 

Address 

Department of Medicine, LSU School of Medicine at New Orleans, LA 70112-2822, USA. 

Source 

Semin Arthritis Rheum, 28(3):187-92 1998 Dec 

Abstract 

OBJECTIVES: This study was performed to raise awareness among rheumatologists about two autoimmune disorders associated with long-term minocycline therapy that can coexist in the same patient. We provide an update on the occurrence of these disorders, their main characteristics, and the current knowledge of potential pathogenic mechanisms. METHODS: We searched the medical literature in English indexed in MEDLINE from 1966 through April 1998 for the term minocycline combined with each of the following: autoimmune hepatitis (AIH), chronic hepatitis, lupus, systemic lupus erythematosus (SLE), anti-myeloperoxidase (anti-MPO), arthritis, vasculitis, and toxicity. We also reviewed relevant references cited in the articles our search uncovered. RESULTS: We identified over 60 minocycline-induced cases of SLE and 24 cases of minocycline-induced AIH. Both autoimmune disorders coexisted in the same patient in 12 cases reported in the literature and in one case seen at our clinic. These 13 patients were characterized by symmetrical polyarthralgias/polyarthritis, elevated liver enzymes, and positive antinuclear antibodies (ANA); they also were generally anti-histone-negative, and only two patients had perinuclear anti-neutrophil cytoplasmic antibodies (p-ANCA). After withdrawal of minocycline, their symptoms resolved, and abnormal laboratory results normalized or markedly improved. CONCLUSIONS: Although data on the actual prevalence of autoimmune disorders induced by minocycline are not available, numerous case reports or small series deal with such disorders. Probable pathogenic mechanisms for each of these conditions are discussed. 

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85.) Expression of CTLA-4 molecule in peripheral blood T lymphocytes from patients with systemic lupus erythematosus. 

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Author 

Liu MF; Liu HS; Wang CR; Lei HY 

Address 

Department of Internal Medicine, College of Medicine, National Cheng Kung University, Tainan, Taiwan, R.O.C. 

Source 

J Clin Immunol, 18(6):392-8 1998 Nov 

Abstract 

CTLA-4 is a cell surface molecule expressed on activated T cells that is suggested to deliver a negative signal for T cell activation. Since CTLA-4 might be a negative regulator of autoimmune diseases, we investigated its expression on T cells from 20 patients with systemic lupus erythematosus (SLE) by flow cytometric analysis and RT-PCR. We found that although CTLA-4 mRNA was readily detected in all patients and controls, only a very minor subset of T cells expressed detectable surface CTLA-4 molecules in both groups. But patients with SLE had significantly increased percentages of CTLA-4-positive T cells compared with normal controls, implying at least that there was no apparent defective expression of CTLA-4 molecule in human lupus. The kinetics of CTLA-4 expression on T cells stimulated in vitro with PMA plus ionomycin were similar in normal controls and patients with SLE. The expression of CTLA-4 molecules after stimulation increased gradually and peaked at 72 hr. However, the induction of CTLA-4 expression on patients' T cells appeared to be weaker than that of normal individuals. Whether this reflects impaired downregulation by CTLA-4 molecules in SLE patients needs to be clarified further. 

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86.) [Nasal reactivity in systemic lupus erythematosus] 

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Author 

Bruno E; Russo S; Alessandrini M 

Address 

Clinica Otorinolaringoiatrica, Universit`a di Roma Tor Vergata. 

Source 

Acta Otorhinolaryngol Ital, 18(2):96-100 1998 Apr 

Abstract 

The present study was prompted by the fact that alterations in nasal respiration were observed in patients with active Systemic Lupus Erythematosus (SLE). These alterations were most likely of a disreactive nature and, thus, could not be attributed to pathology-induced vasculitic alterations. The study was performed using the case/control method. Patients with active SLE were selected on the basis of reference symptoms (difficulty in nasal breathing) and the absence of any significant alteration in the rhinological objectives. Basal, positioning and evoked (cold water, 5 degrees C) rhinomanometry was performed in line with the standards suggested by the "Committee Report on Standardization of Rhinomanometry". Positional testing of the SLE patients revealed "paradoxical response" (66% in the supine decubitus, 50% homolateral and 56% controlateral). In addition there was a statistically significant (p < 0.05) increase in resistance vs. the control group both in the positional testing and upon cold water stimulation. The authors recognized that the rhinomanometric values found in the SLE patients--index of nasal mucosa disreactivity--confirm the presence of the distonic-vegetative alterations characteristic of aspecific vasomotor rhinopathy. In conclusion, the authors hypothesize on the pathogenic mechanisms behind the clinical and instrumental conditions revealed in light of the documented autonomic neuropathy present in SLE patients. 

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87.) Mycophenolate mofetil suppresses autoimmunity and mortality in the female NZB x NZW F1 mouse model of systemic lupus erythematosus. 

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Author 

McMurray RW; Elbourne KB; Lagoo A; Lal S 

Address 

G.V. (Sonny) Montgomery VAMC, the University of Mississippi Medical Center, Jackson 39216, USA. 

Source 

J Rheumatol, 25(12):2364-70 1998 Dec 

Abstract 

OBJECTIVE: To examine the effects of the immunosuppressant, mycophenolate mofetil (MM), on autoimmunity, glomerulonephritis, and mortality in the female NZB x NZW F1 (B/W) mouse model of systemic lupus erythematosus (SLE). METHODS: The development of murine lupus was assessed during the lifespan of 10 female B/W mice given 200 mg/kg/day of MM compared to 10 female B/W mice given vehicle. At 6 week intervals, mice were examined for weight change, albuminuria, antibodies to DNA, and IgG immunoglobulin levels. Morbidity and mortality were assessed daily. In a parallel study, MM treated and control B/W mice were examined at 18 weeks of age for splenocyte phenotype and adhesion molecule expression, as well as antibody titers and in vitro cytokine production in response to immunization with dinitrophenyl-keyhole limpet hemocyanin (DNP-KLH). RESULTS: The administration of MM was well tolerated without apparent side effects. Weight gain in MM treated and control mice was identical through 36 weeks of age. In the treatment group, MM suppressed the development of albuminuria and anti-DNA antibodies compared to the control animals. There were no significant differences between groups in serum concentrations of total IgG. At 60 weeks of age survival in the MM treated group was 100% compared to 10% in the control group. MM did not alter the percentages of CD4, CD8, or IgM positive splenocytes; however, the percentage of CD4+ T lymphocytes expressing very late antigen 4 and intercellular adhesion molecule 1 was reduced. MM inhibited the antibody response to DNP-KLH immunization in vivo; however, in vitro cytokine production in response to KLH was not suppressed. CONCLUSION: MM suppressed the development of autoimmunity and prolonged lifespan in the female B/W mouse model of SLE. Suppression of autoimmunity was achieved without obvious side effects or altered CD4:CD8 T cell ratios. MM may be a useful primary or adjunctive therapy in human SLE. 

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88.) Prevalence of autoantibodies to ribosomal P proteins in juvenile-onset systemic lupus erythematosus compared with the adult disease. 

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Author 

Reichlin M; Broyles TF; Hubscher O; James J; Lehman TA; Palermo R; Stafford HA; Taylor-Albert E; Wolfson-Reichlin M 

Address 

Arthritis and Immunology Program, Oklahoma Medical Research Foundation, Oklahoma City 73104, USA. 

Source 

Arthritis Rheum, 42(1):69-75 1999 Jan 

Abstract 

OBJECTIVE: To determine the prevalence of anti-ribosomal P (anti-P) proteins in several groups of patients with juvenile-onset systemic lupus erythematosus (SLE) in comparison with the prevalence in adult SLE. METHODS: Serum samples were pooled together from 3 cohorts of patients with juvenile-onset SLE in 3 different medical centers and from a miscellaneous group of juvenile-onset SLE patients whose samples were sent by regional physicians. Sera were studied for the presence of anti-P using 2 assays: Western blot with ribosomes as antigen, and an enzyme-linked immunosorbent assay with the COOH-terminal 22 amino acids of the ribosomal P protein in a multiantigenic peptide format as antigen. Sera found positive by both tests were considered positive for anti-P antibodies. Findings from similar studies involving a large cohort of patients with adult-onset SLE from Oklahoma City were used for comparison. RESULTS: The prevalence of anti-P antibodies in the pooled sample of juvenile-onset SLE sera was 45 of 108, or 42%, while in the adult cohort from Oklahoma City, 20 of 260, or 7.7%, were positive for anti-P (odds ratio [OR] 9.6, P < 10(-8) by Fisher's exact test). In addition, it was shown that 12 of 13 patients with both anti-P and anti-double-stranded DNA (anti-dsDNA) in the juvenile SLE cohort had nephritis, while only 8 of 22 patients without both antibodies were nephritic (OR 21.0, P < 10(-8)). It was also shown that in 9 illustrative cases, the levels of anti-P and anti-dsDNA antibodies usually varied together and in concordance with the clinical activity as measured by the SLE Disease Activity Index (SLEDAI). Finally, anti-P-positive and anti-P-negative patients had a similar prevalence of anti-dsDNA, anti-Ro/SSA, and anti-La/SSB antibodies, but patients with anti-P had a higher prevalence of anti-U1 RNP and anti-Sm (P = 0.041 and P = 0.0385, respectively, by Fisher's exact test). CONCLUSION: Antibodies to ribosomal P protein are more prevalent in juvenile-onset SLE than in adult-onset SLE. Levels of antibodies to ribosomal P protein vary with the clinical disease activity as measured by the SLEDAI, often in concordance with the levels of anti-dsDNA. The presence of both anti-P and anti-dsDNA antibodies was powerfully associated with nephritis in the cohort of patients for whom comprehensive clinical and serologic data were available. 

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89.) Trends in the incidence and mortality of systemic lupus erythematosus, 1950-1992. 

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Author 

Uramoto KM; Michet CJ Jr; Thumboo J; Sunku J; O'Fallon WM; Gabriel SE 

Address 

Mayo Clinic, Rochester, Minnesota 55905, USA. 

Source 

Arthritis Rheum, 42(1):46-50 1999 Jan 

Abstract 

OBJECTIVE: To describe trends in systemic lupus erythematosus (SLE) incidence and mortality over the past 4 decades. METHODS: Using the Rochester Epidemiology Project resources, medical records were screened to identify all Rochester, Minnesota residents with any SLE-associated diagnoses, discoid lupus, positivity for antinuclear antibodies, and/or false-positive syphilis test results determined between January 1, 1980 and December 31, 1992. Medical records were then reviewed using a pretested data collection form in order to identify cases of SLE according to the American College of Rheumatology 1982 revised criteria for SLE. Drug-induced cases were excluded. All identified SLE patients were followed up until death, migration from the county, or October 1, 1997. These data were combined with similar data from the same community obtained between 1950 and 1979, and trends in the SLE incidence and mortality over time were calculated. RESULTS: Of the 430 medical records reviewed, 48 newly diagnosed cases of SLE (42 women and 6 men) were identified between 1980 and 1992. The average incidence rate (age- and sex-adjusted to the 1970 US white population) was 5.56 per 100,000 (95% confidence interval [95% CI] 3.93-7.19), compared with an incidence of 1.51 (95% CI 0.85-2.17) in the 1950-1979 cohort. The age- and sex-adjusted prevalence rate as of January 1, 1993 was approximately 1.22 per 1,000 (95% CI 0.97-1.47). Survival among SLE patients was significantly worse than in the general population (P = 0.017 compared with the 1980-1992 cohort, and P < 0.0001 compared with the 1950-1979 cohort, by log-rank test). Cox proportional hazards modeling demonstrated a statistically significant improvement in the survival rate over time (P = 0.035). CONCLUSION: Over the past 4 decades, the incidence of SLE has nearly tripled, and there has been a statistically significant improvement in survival. These findings are likely due to a combination of improved recognition of mild disease and better approaches to therapy. 

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90.) Antithrombin, protein S and protein C and antiphospholipid antibodies in systemic lupus erythematosus. 

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Author 

Costallat LT; Ribeiro CC; Annichino-Bizzacchi JM 

Address 

Departament of Internal Medicine, State University of Campinas, UNICAMP, Brasil. 

Source 

Sangre (Barc), 43(5):345-8 1998 Oct 

Abstract 

Patients with systemic lupus erythematosus (SLE) have an increased risk of thrombosis, related to the lupus anticoagulant or anticardiolipin antibodies (ACL). Antithrombin (AT), protein C (PC) and protein S are natural anticoagulants with a very important role in the regulation of coagulation and fibrinolysis, and in the prevention of thrombosis. Total protein S (TPS), free protein S (FPS), AT and PC were measured in 53 unselected patients with SLE in order to verify their relation with previous history of thrombosis or the presence of anticardiolipin antibodies (ACL). The influence of prednisone use on the concentration of these natural anticoagulants was also analysed. The control group was formed by 20 blood donors. The PC concentration was increased in patients with ACL, when compared to controls (p < 0.01), or patients without ACL (p = 0.01). FPS levels were decreased in patients with SLE in relation to controls (p = 0.01), but not related to thrombosis or ACL. There was no difference in plasmatic concentration of AT and TPS, between patients and controls. PC, AT and TPS were increased in patients under prednisone use (p < 0.01). There was no association between concentration of natural anticoagulants and a history of thrombosis. Although decreased FPS was found, or results suggest that it seems not to be a risk factor for thrombosis in SLE. Since PC and AT were not decreased, they should not be involved with thromboembolic complications in these patients. The use of prednisone can influence concentration of natural anticoagulants in patients with SLE. 

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DATA-MÉDICOS/DERMAGIC-EXPRESS No (54) 10/05/99 DR. JOSE LAPENTA R. 

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Produced by Dr. José Lapenta R. Dermatologist
Venezuela 1.998-2.024

Producido por Dr. José Lapenta R. Dermatólogo Venezuela 1.998-2.0024

Tlf: 0414-2976087 - 04127766810