Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0024141 (systemic lupus erythematosus)
 44,322 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

With a few exceptions, there remains a paucity of good epidemiological studies from India and South-East Asia. The overall impression is that the prevalence of rheumatoid arthritis (RA) is slightly less compared with the West and follows a milder course. There may be differences in the articular expression of the disease with the wrist and forefoot less commonly affected than in Caucasian studies. Extra-articular manifestations and erosive change are less frequent and severe. HLA DR4 does not correlate with seropositivity and severity of RA. The prevalence of SLE may be less in the Indian subcontinent than in the West. However, recent indications are that in South-East Asia and the Pacific region the prevalence morbidity and mortality are higher than in developed countries. An improvement in socio-economic conditions may be accompanied by an improvement in the survival of patients with SLE.
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PMID:Rheumatoid arthritis and connective tissue disorders: India and South-East Asia. 772 87

Recent studies have suggested an association between primary antiphospholipid syndrome (PAPS), antiphospholipid antibodies and some major histocompatibility complex (MHC) antigens. We have studied the relationship between MHC class II antigens and PAPS in 19 patients from the south of Spain. Univariant analysis showed an association between PAPS and HLA-DQ7 (47% vs 25%l P = 0.3), DR4 (32% vs 16%; P = 0.08) and DQ3 (63% vs 39%; P = 0.04). However, multivariant analysis confirmed the association with DQ7 (RR = 2.5; CI 80%: 1.3-4.7) and DR4 (RR = 2.2; CI 80%: 1.1-4.4) but not with DQ3. When we introduced DRw53 into this analysis, we noticed a DR4 confounding effect, with DQ7 (RR = 3.1; CI 80%: 1.7-5.8) and Drw53 (RR = 2.3; CI 80%: 1.2-4.4) remaining as the most important HLA antigens related to PAPS. In conclusion, in PAPS patients from the South of Spain, HLA-DQ7 antigen showed the highest relative risk for PAPS, followed by DRw53.
Lupus 1995 Feb
PMID:Association between HLA class II antigens and primary antiphospholipid syndrome from the south of Spain. 776 40

1. Graft survival was similar at one year for the various diseases, but at 3 years, a 16% divergence was noted among diseases. IGAN patients had the highest graft survival rate. 2. Graft survival rates of IGAN, ALP, and PC in Black and White patients were similar, but in all other diseases, a high loss rate was seen after one year among Black patients. 3. Patient survival was almost identical for the various diseases among Whites and Blacks. 4. SLE patients with DR2 or DR3 had higher graft survival rates than SLE patients without these groups (p < 0.05 in Whites). 5. IDDM patients with DR3 or DR4 had higher graft survival rates than IDDM patients without these groups (p < 0.05 in Whites, p = ns in Blacks). 6. Nephrosclerosis patients with DR2 or DR4 had higher graft survival rates than those who did not (p = ns in Whites, p < 0.05 in Blacks). 7. CGN patients with DR1 had higher graft survival rates than CGN patients without DR1 (p < 0.00005 in Whites). 8. IDDM patients with SPK transplants had higher graft survival rates than IDDM patients grafted with a KAT (p < 0.000001). In recent years, almost 30% of IDDM patients had SPK transplants. 9. Patients with SPK grafts compared to KAT were younger, White, were more often DR3/4, and worked full-time. 10. The SPK effect was seen only at the excellent centers. At all other centers, SPK and KAT patients had the same graft survival rates.
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PMID:The long-term effect of primary disease on cadaver-donor renal transplant recipients. 791 83

In rheumatic disease, monoclonal antibodies have been used for the treatment of refractory rheumatoid arthritis, systemic lupus erythematosus, unresponsive vasculitis and relapsing polychondritis. Our greatest experience has however been with rheumatoid arthritis. After molecular engineering, hybrid monoclonal antibodies constructed from animal sources become largely human, and thus well tolerated, and highly specific. They can be focused selectively to particular targets, but the problem is to identify the causative antibody. In rheumatoid arthritis, we do know a great deal about the pathogenesis of the disease and rational targets can be selected. The major histocompatibility complex class II molecules would theoretically be the most effective target, but no specific antigen has been identified. Total blockade of all class II molecules would probably result in unacceptable immunosuppression. Despite this handicap, anti-HLA-DR4 monoclonal antibodies have been used in humans in an attempt to generate an anti-idiotypic response against DR4. T lymphocytes are known to play a major role in the pathogenesis of rheumatoid arthritis, thus targeting their surface markers would be a reasonable approach to monoclonal antibody therapy. Trials have been conducted using antibodies against the surface markers CD7, CD5, CDw52 and CD4. Further work has centered on differentiation antigens. Preliminary evidence suggests anti-interleukin-2-receptor monoclonal antibodies may be effective in rheumatoid arthritis. There have also been reports of attempts at anti-cytokine immunotherapy. Adhesion molecules would be another potential target. The ongoing trials have given us much insight into the pathogenesis of rheumatoid diseases and led us to the stage where we are now attempting to identify appropriate therapeutic regimes and combinations to maximise patient benefit. At present, we must continue our research for the causative antigen.
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PMID:Monoclonal antibody therapy in rheumatic disease. 802 42

Presence of autoimmune diseases and relationship of autoantibody expression with HLA association has been studied in 44 multicase rheumatoid arthritis (RA) families of Asian Indian origin. An increased prevalence of systemic lupus erythematosus (SLE) was observed in relatives (2.3%). Although HLA-DR4 segregated preferentially with seropositivity in general, no difference was observed among seropositive versus seronegative RA. On the other hand, no HLA association was observed with ANF positivity in these families. An increased frequency of DR7 in the ANF negative and RF negative group of RA patients compared to positive groups suggests that it may act as protective element for the development of autoantibodies in RA. An increased occurrence of DR4 in relatives affected with SLE was observed. While RA segregated mostly with HLA-DR4 in these families, autoimmune thyroid disease and insulin dependent diabetes mellitus (IDDM) segregated with HLA-DR3 suggesting the involvement of at least two sets of HLA-linked autoimmunity favouring susceptibility genes in the Indian population.
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PMID:Occurrence of autoimmune diseases and relationship of autoantibody expression with HLA phenotypes in multicase rheumatoid arthritis families. 835 6

Whether a genetic predisposition to develop the antiphospholipid syndrome (APS) and to produce anticardiolipin antibodies (aCL) and lupus anticoagulant (LAC) exists has been addressed by family studies and by population studies on primary APS and on aCL in diseases other than primary APS. Various studies suggest a familial occurrence of aCL and LAC, with or without clinical evidence of APS. This familial tendency could be genetically determined, because APS, aCL, and LAC occur in families carrying haplotypes which contain HLA-DR4, -DR7, and -DRw53. Population studies on primary APS also indicate that HLA genes have a role in conferring susceptibility to develop primary APS. Again, DR4, DR7, and DRw53 are the relevant loci. Population studies on aCL in diseases other than primary APS indicate that aCL are associated with DR4, DR7, and DRw53, at least when they are found in patients with systemic lupus erythematosus. Because HLA-DR4, -DR7, and -DRw53 are in linkage disequilibrium, the genetic association of aCL could be with DRw53 and, depending on the regional frequency of DR4 or DR7, it could be linked with either DR4 or DR7. HLA-DR4 seems to be more important in Anglo-Saxons, whereas DR7 emerges in populations of Latin origin. In this report we review our studies and the pertinent literature in this field.
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PMID:The immunogenetics of the antiphospholipid syndrome, anticardiolipin antibodies, and lupus anticoagulant. 879 13

The cause of toxic oil syndrome (TOS) has not yet been definitively determined, but some genetic susceptibility factors (certain HLA antigens and female sex) have been identified in 236 patients. Similarities with genetic factors for scleroderma and hydralazine-induced lupus (i.e. in TOS female sex and HLA-A24, Pcorrected = 0.00001 and DR4, Pcorrected = 0.04, respectively) may provide a clue to the responsible xenobiotic and its pathogenesis, and may also help in understanding the basis of the related eosinophilia-myalgia syndrome associated with tryptophan ingestion. In this paper it is also established that a human class I antigen (HLA-A24) and, independently, an HLA class II haplotype (DR4-DQ8, Pcorrected = 0.04) and arginine 52 in the alpha-DQ chains (Pcorrected = 0.03) are associated with TOS susceptibility, similarly to insulin-dependent diabetes. This further supports the classification of TOS as an autoimmune disease. Also, the increased frequency of a particular set of low-frequency HLA class I antigens in chronic TOS patients (i.e. B27, B37, B38 and B49) and the probable decrease in the frequency of HLA-B homozygotes in surviving patients (Pcorrected = 0.008) may provide an objective model to explain the maintenance of the HLA polymorphism: less frequent HLA alleles may be more advantageous in the event of unexpected human contact with unusual xenobiotics (not only microbes); however, other mechanisms working together to preserve and generate HLA polymorphism may coexist.
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PMID:Frequencies of HLA-A24 and HLA-DR4-DQ8 are increased and that of HLA-B blank is decreased in chronic toxic oil syndrome. 880 34

Alleles of the major histocompatibility complex (MHC) have been recognized as genetic factors for the development of SLE. The [HLA-B8; SC01; DR3] extended haplotype seems to be relevant in patients from white European descent, pertinent alleles, however, are difficult to select on haplotypes with linkage disequilibrium. Studies in non-Caucasian patients are therefore mandatory. Admixture estimates in Mexicans have shown a proportion of 56% of Indian genes, 40% of Caucasian genes and from 4 to 12% of Black genes. In order to determine the relevant MHC loci in the genetic susceptibility for SLE we studied Class I, II and III alleles in 102 Mexican SLE patients and 350 of their first degree relatives and compared these two groups to another one composed by 200 ethnically matched normal individuals. We found significantly increased frequencies of HLA-DR3 (pC = 0.03, RR = 2.56) and DR7 (pC = 0.004, RR = 3.08) in SLE patients as compared to controls. On the other hand, first degree relatives had a significantly increased frequency of HLA-DR7 (pC = 0.01, RR = 2.98). There were 21 out of 33 HLA-DR3 haplotypes with complotypes other than SC01 and 25 out 37 SC01 haplotypes with DR alleles other than DR3. Nevertheless, [SC01; DR3] haplotypes were also increased (pC = 0.01, RR = 12.4). After removing [HLA-B8; SC01; DR3] haplotypes, DR3 was the only allele that remained significantly increased (p = 0.04, RR = 2.1). We also found in SLE patients significantly decreased frequencies of the autochthonous Mexican alleles (A30, B39 and DR4) and no deviation from normality of any of the HLA-DQ alleles. These data suggest a fundamental role of the HLA-DR3 allele in the predisposition to SLE in Mexican patients which might be hightened by genes located around the class III MHC region. They also substantiate the pertinence of ethnic admixture estimates in modern human populations.
Lupus 1996 Jun
PMID:The role of HLA-DR alleles and complotypes through the ethnic barrier in systemic lupus erythematosus in Mexicans. 880 88

The human TNF genes are located within the MHC class-III region on chromosome 6. The presence or absence of an Nco-I restriction site in the 5' non-coding sequence of the TNF beta gene defines two alleles (TNFB*1 and TNFB*2). The segregation of these alleles has been associated with levels of TNF alpha or TNF beta production in systemic lupus erythematosis (SLE), insulin-dependent diabetes mellitus (IDDM) and in healthy control individuals. Rheumatoid arthritis (RA) is characterized by high levels of TNF alpha within the synovial fluid and to address the question of whether this could be brought about by a genetic predisposition to high TNF production by RA individuals, we examined the distribution of this Nco-I polymorphism in 98 healthy volunteers and 123 patients with active rheumatoid arthritis. No difference was observed between the normal and RA groups with respect to haplotype segregation or allelic frequency. Furthermore, no difference was observed between DR4+ or DR4- individuals in the control or RA groups. These data demonstrate that the high level of TNF alpha seen in the joints of RA patients is unlikely to be due to a genetic predisposition of these patients to high TNF alpha production, as defined by the TNF Nco-I restriction fragment length polymorphism (RFLP).
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PMID:TNF Nco-I RFLP is not an independent risk factor in rheumatoid arthritis. 909 56

We analyzed structural motifs of peptides bound to HLA-DR4 (DRB1*0405 and DRB1*0406) and DR9 (DRB1*0901) and found that: (a) AxxBxC motif where A, B, and C are hydrophobic, hydrophobic, and neutral, respectively, is important for binding to DR4; (b) Gln (Q) or Ser at position C allow high-affinity binding specific to DRB1*0406 which is strongly associated with insulin autoimmune syndrome; (c) among human insulin-derived peptide fragments, the TSICSLYQLE of the human insulin alpha chain, which is exposed only under reducing conditions, has the highest affinity specific to DRB1*0406 by binding with the IxxLxQ motif; (d) a short-term human insulin-specific T cell line recognizes a peptide fragment containing the IxxLxQ motif as a major T cell epitope; and (e) in the AxxB motif, where A and B need to be hydrophobic for binding to DR9, neutral Ser is exceptionally allowed at position B. The implications of our results are discussed in light of the HLA-DR4-associated susceptibility to insulin autoimmune syndrome and HLA-DR9-associated susceptibility to juvenile-onset myasthenia gravis and systemic lupus erythematosus with antiphospholipid syndrome, in particular T cell responses to autoantigens.
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PMID:Molecular mechanisms underlying HLA-DR-associated susceptibility to autoimmunity. 911 30


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