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

In order to find potential correlations between HLA class II alleles and anti-SS-A, -SS-B, -Sm and anti-snRNP responses among Norwegian patients with systemic lupus erythematosus (SLE), HLA-DRB1, -DRB3*0101, -DQA1 and -DQB1 alleles were determined by DNA typing 50 patients and 108 controls. HLA distributions were analysed in the following autoantibody subgroups: anti-SS-A with -SS-B, anti-SS-A without -SS-B, anti-snRNP without -Sm, anti-SS-A without -snRNP and anti-snRNP without -SS-A. The autoantibodies were detected by EIA (enzyme immunuassay). Patients with anti-SS-A and -SS-B had significantly increased frequencies of DRB1*03, DRB3*0101, DQA1*0501, DQB1*0201 (in linkage disequilibrium) versus controls and versus patients without anti-SS-A and -SS-B. No differences in HLA distribution were found when the group with anti-SS-A alone was compared to the group with anti-SS-A and concomitant -SS-B. Comparing the groups with and without anti-SS-A and -SS-B, the highest RR were found for the alleles DRB1*03, DRB3*0101, DQB1*0501, DQB1*0201 (in linkage disequilibrium) with RR: 16.8, 5.0, 19.6, 10.3, respectively, P < 0.05). RR for DQw2/DQw6 heterozygotes was 3.5 (Ns.), and RR for cases having DQ alpha molecules with glutamine in position 34 and DQ beta molecules with leucine in position 26 on both chains was 6.3 (P < 0.05). No HLA associations were observed in the group with anti-snRNP without concomitant -Sm or without concomitant -SS-A. These results show that production of anti-SS-A and -SS-B is associated to the HLA alleles DRB1*03, DRB3*0101, DQA1*0501, DQB1*0201, and that this haplotype shows stronger correlation to these responses than DQw2/DQw6 heterozygosity or HLA molecules having glutamine in position 34 (DQ alpha) and leucine in position 26 (DQ beta). The failure to observe any correlation with DRBI*15,16 (DR2) in the group with anti-SS-A alone may demonstrate ethnic differences concerning this response. The failure to identify any HLA associations for the anti-snRNP response may reflect the heterogeneity of the molecules that constitute this antigen.
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PMID:Distributions of HLA class II alleles in autoantibody subsets among Norwegian patients with systemic lupus erythematosus. 748 63

Our objective was to study the interaction between major histocompatibility complex (MHC) class II and T-cell receptor (TCR) alleles in the recognition of extractable nuclear antigen-derived peptides in 32 patients with systemic lupus erythematosus and 173 of their family members. MHC genes were analyzed using sequence specific oligonucleotides, and TCR beta-chain gene polymorphism using restriction fragment-length polymorphism. One dominant peptide (as defined by enzyme-linked immunosorbent assay autoantibody reactivity) was identified in each antigen studied: peptide 1-20 in Sm-D, peptide 35-58 in U1-RNP-A, and peptide 304-324 in the Ro/SSA 60 Kd protein. None of the MHC class II and TCR beta haplotypes was directly associated with any of the autoantibodies. Twenty-six subjects had antibodies to the peptide Sm-D1-20; nine of them were DRB1*0101/DQB1*0501. Among subjects with this haplotype, the number of responders was higher (p < 0.028, p corrected, pc = 0.336) in those with the 2-25-9 TCR beta haplotype than in the remainder. Conversely, the number of DRB1*04/DQB1*0302 responders was lower (p < 0.030, pc = 0.360) among subjects with the 23-20-9 TCR beta haplotype than in those without. The odds ratios (OR) were 4.23 and 0.21, respectively. Of the 54 subjects positive for anti-U1-RNP-A 35-38, 13 were DRB1*0101/DQB1*0501 and eight DRB1*04/DQB1*0302. The percentage of responders was higher (p < 0.041, pc = 0.492, OR = 3.48) in the former group of subjects with the 2-25-9 TCR beta haplotype, and lower (p < 0.02, pc = 0.024, OR = 0.09) in the latter with the 23-20-9 TCR beta haplotype. Three of the 12 anti Ro/SSA 60Kd 304-324-positive subjects were DRB1*0101/DQB1*0501. All had the 2-25-9 TCR beta haplotype (p < 0.046, pc = 0.552, OR = 6.29) and none the 23-20-9 (p < 0.031, pc = 0.372, OR = 0.10). The same combinations of genes were associated with high/low response toward the three peptides. These data provide evidence for an interplay of the MHC class II and TCR beta alleles in the control of specific autoantibody response to well-defined nuclear Ag peptides.
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PMID:Interaction between certain major histocompatibility complex class II and T-cell receptor V beta alleles promotes the antibody production to extractable nuclear antigen-related peptides. 902 5

The objective of this project was to determine the association of the DQA1*0501 allele in the susceptibility to develop systemic lupus erythematosus (SLE) in Mexicans. Frequencies of generic MHC Class II genes (HLA-DR, DQA and DQB1) were determined by DNA typing in 58 Mexican mestizo SLE patients and 96 ethnically matched controls. Statistical analysis was performed by chi-square and Fisher's exact tests. The DQA1*0501 allele was found to be in linkage disequillibrium with H LA-DR3, DR11, and DR14. This explains the lack of association with the allele alone, and the evident strong association of SLE with the [HLA-DR3-DQA1*0501-DQB1*0201] and [HLA-DR1-DQA1*0101-DQB1*0501] haplotypes. It was also found a significant decrease (protection) of the [HLA-DR8-DQA1*0401-DQB1*0402] haplotype which is known to be a characteristic haplotype among the indigenous population of Mexico. These data shows that the susceptibility to SLE in Mexicans is more strongly influenced by the MHC haplotypes than by single alleles. The suggestion that these genes do not act alone but in combination, makes the identification of haplotypes mandatory.
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PMID:Haplotype distribution of class II MHC genes in Mexican patients with systemic lupus erythematosus. 980 2

The frequency of the HLA class II antigens/alleles (HLA-DR, DQ and DP) were studied in 70 Malaysian Chinese patients with systemic lupus erythematosus (SLE) to examine the contribution of these genes to disease susceptibility, their clinical expression and Immunological responses. This was done using modified PCR-RFLP technique. These samples were then compared with 66 ethnically matched controls. We found a strong association of the DQA1*0102 (p corr = 0.032, rr = 3.39), DQB1*0501 (p corr = 0.003, rr = 4.55), *0601 (p corr = 0.006, rr = 4.22) and DPB1* 0901(p corr = 0.02, rr = 4.58) with SLE. Clinically, we found a strong association of DR2 and DQA1*0301 with renal involvement and DQA1*0102 with alopecia. Immunologically, statistical analysis (Chi-square test ) showed a strong association of DQA1*0102 with anti-Ro/La antibodies while DQA1*0301 was observed to be strongly associated with antibodies to ds DNA. DQA1*0102 was found more frequently in those with a later disease onset (30 years of age or above). From these data we suggest that the HLA class II genes play a role in conferring disease susceptibility and clinical and immunological expression.
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PMID:The association of the HLA class II antigens with clinical and autoantibody expression in Malaysian Chinese patients with systemic lupus erythematosus. 1169 26

In this study, we investigated the association of HLA-DRB1 and DQB1 with Thai patients with SLE. A highly significant increase in the frequency of DRB1*1502 and DQB1*0501 was found in SLE patients compared with normal controls. DRB1*1501 and DRB1*1602 were also slightly increased. In contrast, DRB1*1202 and DQB1*0301 were decreased, and DRB1*0406 and DRB1*1401 were not found in the patients' group. The haplotype analysis revealed that DRB1*1502 - DQB1*0501 was most strongly associated with SLE, and also suggested a primary role for DRB1 rather than DQB1. Taken together with the previous report which demonstrated the association of the same haplotype in Taiwan, our present observations strongly suggested that DRB1*1502 - DQB1*0501 is the major HLA haplotype that confers susceptibility to SLE in the South-east Asian populations.
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PMID:Association of HLA-DRB1*1502-DQB1*0501 haplotype with susceptibility to systemic lupus erythematosus in Thais. 1202 37

Abstract The relation between HLA class II alleles and clinical findings were examined in Japanese patients with systemic lupus erythematosus (SLE). In 284 patients with multicenter SLE, HLA class II alleles were examined using the DNA typing method, and the results were compared with the clinical findings. The frequency of DRB1*0101 and DQB1*0501 significantly increased in male patients, and that of DRB1*0803 significantly increased in patients over 50 years of age. In relation to cutaneous manifestations, there were positive photosensitivity associations with DQA1*0101 and/or DQA1*0301, malar rash with DQA1*0101 and/or DRB1*0901, alopecia with DQA1*0101, skin ulcers with DRB1*0401, and oral ulcers with DQA1*0301. In addition, there were also positive associations of myalgia with DRB1*1406 and negative associations of aseptic bone necrosis with DQA1*0601, and hepatomegaly with DRB1*0405 and/or DQA1*0401. In relation to laboratory findings, there were positive associations of hemolytic anemia with DRB1*1402 and negative associations of leukopenia with DQA1*0601, lymphopenia with DQA1*0301, and proteinuria with DRB1*0901. Interestingly, DQA1*0101 and/or DQB1*0501 were significantly associated with WHO classification type II rather than type IV. In patients with SLE, some HLA types related to clinical or laboratory findings.
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PMID:Multicenter cooperative study of HLA class II alleles in Japanese patients with systemic lupus erythematosus. 2438 36