Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0003873 (rheumatoid arthritis)
 53,068 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Collagen-induced arthritis (CIA) is an animal model of auto immune polyarthritis, sharing similarities with rheumatoid arthritis (RA). Paradoxally, susceptibility to mouse CIA is controlled by the H2A loci (DQ homologous) while RA is linked to HLA.DR genes (H2E homologous). We recently showed that the E beta d molecule prevents CIA development in susceptible H2q mice. We addressed the question of whether H2Eb polymorphism will influence CIA incidence as HLA.DRB1 polymorphism does in RA. In F1 mice, only H2Ebd and H2Ebs molecules showed protection. Using recombinant B10.RDD (Ebd/b) mice, we found that CIA protection was mediated by the first domain of the E beta d molecule. Using peptides covering the third hypervariable region of the E beta chain, we found a perfect correlation between presentation of E beta peptides by the H2Aq molecule and protection on CIA. Therefore, the mechanism by which H2Eb protects against CIA seems to rely on the affinity of E beta peptides for the H2Aq molecule.
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PMID:Polymorphism of the MHC class II Eb gene determines the protection against collagen-induced arthritis. 779 66

To determine the HLA-DRB1 04 and HLA-DQB1 03 variants associated with rheumatoid arthritis (RA) among Russians who live in West Siberia, we studied patients with RA using the polymerase chain reaction and dot-blot hybridization with oligonucleotide probes. A significant increase was seen only for DRB1 0404/08, although the predominant variant in DR4+ RA patients was DRB1 0401. We found no significant difference in the DQB1 03 variants in RA cases when compared with controls. The results suggest that in the Russian-Siberian population RA is primarily associated with several DRB1 04 variants that share sequence identity in the third hypervariable region.
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PMID:Oligonucleotide genotyping of HLA-DRB1 04 and HLA-DQB1 03 among Russians in west Siberia suffering from rheumatoid arthritis. 785 64

The third hypervariable region (HV3) of HLA-DRB1*0401 helps the development of severe rheumatoid arthritis by an unknown mechanism. To test whether the third hypervariable region of HLA-DRB1*0401 may shape the T cell repertoire, we studied proliferative responses to peptides encompassing the third hypervariable region of seven HLA-DRB1 alleles in normal subjects and patients with rheumatoid arthritis. We found that, in general, there is no tolerance to peptides from the third hypervariable region of self-HLA-DRB1 alleles. However, a peptide from the third hypervariable region of DRB1*0401 (DRB1*0401 HV3 peptide) is tolerated in people who express HLA-DRB1*0401. Indeed, PBMCs from people who express DRB1*0401 do not proliferate to DRB1*0401 HV3 peptide. Conversely, people who express DRB1*1501 respond to DRB1*0401 HV3 peptide. Finally, people who express both DRB1*0401 (nonresponder haplotype) and DRB1*1501 (high responder haplotype) do not respond to DRB1 HV3 peptide, thus demonstrating tolerance. Therefore, the third hypervariable region of HLA-DRB1*0401 shapes the T cell repertoire.
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PMID:Tolerance to a self-peptide from the third hypervariable region of HLA DRB1*0401 in rheumatoid arthritis patients and normal subjects. 796 84

HLA-DR4 gene was studied by polymerase chain reaction method in 95 patients with rheumatoid arthritis(RA) and 130 normal controls in a Shanghai population. The results showed that the DR4 was significantly associated with RA(RR = 3.1, chi 2 = 13.8, P < 0.005). The second exon of DR4 gene was also analysed by PCR-RFLP technique. There were at lest eight DR4 subtypes in this Chinese population. The DRB1 *0405 (Dw15) was the most common allele, accounting for 48% of DR4 positive normal individuals and also is a principal subtype associated with RA susceptibility (RR = 3.1, P < 0.005). Analysis of the third hyperpolymorphic region of DR4 positive samples showed that 92% of patients had a sequence encoding amino acids RRAA or KRAA compared with 56% of the DR4 positive controls (chi 2 = 10.29 P < 0.005). All subtypes that were positively associated with RA susceptibility had the RRAA (DRB1* 0404, 0405. 0408 and 0410) or KRAA (DRB1 * 0401) sequences, while the negatively associated ones (DRB1 0402, 0403 and 0406) had not. As a further evidence, it strongly supported the "shared epitope" hypothesis. The different DR4 subtype structures and frequencies may account for the different associations of DR4 with RA in various ethnic groups.
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PMID:[The molecular basis of HLA DR4 alleles associated with rheumatoid arthritis in a Chinese population]. 798 17

Associations of HLA antigens with many of the rheumatic diseases have been established over the last two decades. Although these discoveries provide potential new insights into disease pathogenesis, the clinical utility of HLA typing has been limited. The major exception is that of HLA-B27 in the spondyloarthropathies, where clinical uses of HLA-B27 testing has permitted identification of a large spectrum of disease that was previously misdiagnosed and misclassified. HLA-B27 remains potentially useful in the diagnosis of atypical spondyloarthropathies because of its high frequency in patients with these diseases (yielding good sensitivity) and its relatively low frequencies in most normal populations (yielding good specificity). Its predictive value in individual cases, however, depends on the quality of the physician's assessment of the likelihood of a spondyloarthropathy. In patients with juvenile-onset arthritis, typing for HLA-B27, as well as several HLA-class II alleles (DR5, DR8, DP2, and DP3), may prove to be useful in diagnosis and classification; however, additional studies are necessary. HLA oligotyping of DNA in patients with early rheumatoid arthritis to determine homozygosity versus heterozygosity for the DRB1 susceptibility sequence promises a potential new parameter for predicting clinical disease severity, and thus the possible early initiation of more aggressive therapies. Additional studies are necessary, however, to determine the validity of this approach. Finally, the future diagnosis, prevention, and treatments of these diseases may depend on the identification and manipulation of specific immune responses mediated by HLA molecules, thus making HLA typing for clinical purposes routine.
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PMID:Histocompatibility typing in the rheumatic diseases. Diagnostic and prognostic implications. 801 17

Seventy-two patients with rheumatoid arthritis (RA) and 82 controls have been typed with the XI Histocompatibility Workshop DRB1 and DQB1 sequence-specific oligonucleotide probes. The increase of DRB1*04 corresponds to an increase of the serologically defined DR4, previously found in a small group of Zimbabwean RA patients and we now show that this increase is due to the subtype DRB1*0405 in association with DQB1*0302. In addition there is a clearcut increase of DRB1*1001 equivalent to the serologically defined DR10. There was no increase amongst RA patients of DRB1*0102 which was the predominant DR1 sub-type amongst controls. In the course of our investigation, we observed a DRB1*04 variant which corresponds to DRB1*0412, newly defined in the XIth Histocompatibility Workshop.
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PMID:Sequence-specific oligonucleotide typing in Shona patients with rheumatoid arthritis and healthy controls from Zimbabwe. 836 8

Rheumatoid arthritis (RA) is associated with the HLA-DR4 cellular subtypes Dw4 and Dw14 in Caucasians, with Dw15 in Japanese, and possibly with HLA-DR1 in Israeli Jews. Sequencing studies in Caucasians have shown that these molecules share a common amino acid sequence in the third hypervariable region of the DR molecule (AA 67-74: LLEQRRAA or LLEQKRAA), suggesting that this sequence is primarily associated with RA. An important argument in favor of this shared-epitope hypothesis has been the reported association between DR1 and RA in Israeli Jews. However, a later report did not confirm this association, and cellular typing showed that Israeli DR1 consists of three or more subtypes, suggesting that new subtypes might be present. Since no sequencing data on Israeli HLA-DR1 genes have been reported, we sequenced the first domain (AA 10-91) of the DRB1 gene in 12 DR1-positive Israeli RA patients, 5 healthy controls and a homozygous typing cell (HTC), defining the major Jewish cellular HLA-DR1 subtype. DRB1*0102 (DR1 Dw20) was found in 8 RA patients, 3 controls and the HTC "LVA". DRB1*0101 (DR1 Dw1) was found in 4 RA patients and 2 controls. No other DR1 subtypes were encountered. In all 20 DR1 haplotypes, the DRB1*0101 or 0102 allele was associated with DQA1*0101 and DQB1*0501, being identical to the Caucasian DR1 haplotypes. Thus, at the sequence level, we found no basis for the reported extensive cellular heterogeneity of DR1 in the Israeli population.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:HLA-DR1 and rheumatoid arthritis in Israeli Jews: sequencing reveals that DRB1*0102 is the predominant HLA-DR1 subtype. 845 40

The second exon of the DRB1 gene encoding for the first domain of the HLA-DR beta 1-chain was sequenced in 16 patients (10 DR4/DR1 positive, 6 DR4/DR1 negative) with seropositive rheumatoid arthritis (RA). We could confirm the strong association of susceptibility to RA with functionally equivalent conformations on otherwise distinct MHC molecules. At least one HLA-DR allele in all of the analysed DR4 or DR1 positive patients showed such an epitope with a minimal variability limited to residue 71. However, in HLA-DR4 and -DR1 negative patients such a similar epitope could not be detected.
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PMID:HLA-DRB1 gene sequences in HLA-DR4 positive and negative patients with rheumatoid arthritis. 849 71

Adult rheumatoid factor (RF) positive rheumatoid arthritis (RA) and RF positive arthritis of childhood are associated with DRB1*0401 in Caucasians, and DRB1*0405 in Orientals, and in Ashkenazi and nonAshkenazi Jews. Certain other DRB1 alleles (DRB1*0101,1001) which have a similar sequence in the 3rd hypervariable region of the 1st domain are also associated with RA, but they appear to function as weaker risk factors. The difference in the relative strength of the associations is likely to be due to structural differences in the 1st and 2nd variable regions of the first domain of these alleles. Similarities and differences in the HLA associations between North American Caucasoid patients with juvenile arthritis in Dallas, TX, USA, and in Prague, Czechoslovakia, are discussed.
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PMID:Sequences of HLA alleles associated with arthritis in adults and children. 850 55

To reveal immunogenetic factors involved in the pathogenesis of rheumatoid arthritis(RA), two hundreds and four unrelated Japanese patients with RA were typed for HLA by both serologic typing and DNA typing using polymerase chain reaction-sequence specific oligonucleotide probe (PCR-SSOP) method. Serologic HLA typing data showed that frequencies of HLA-A11, DR4, DR53, and DQ4 were increased and those of DR8, DR52, and DQ1 were decreased in the patient group. The HLA-DNA typing has defined more precisely the disease-associated HLA-class II alleles and revealed that DRB1*0405, DQA1*03, and DQB1*0401 were strongly associated with the disease susceptibility whereas DRB1*0803, DQA1*0103, and DQB1*0601 showed negative association with RA. Comparison of amino acid sequences of DRB1*0405 with other DRB1 alleles suggested that the risk for RA was closely associated with particular amino acid residues of DR beta chain, i. e. glycine residue at the 86th position in addition to the residues between 70th and 74th position. The significant decreased frequency of DRB1*0803 in the DRB1*0405 positive patient group suggests that DRB1*0803 may control resistance to RA as a dominant genetic trait. In addition, the observation that the frequency of DPB1*0201 was increased in the DRB1*0405 negative patient group may indicate that the disease susceptibility to RA is controlled by the HLA-DP region in the minority of the patients. The polymorphism of TAP2 gene and TCR genes showed no significant association with RA, suggesting that the contribution of these genes to the susceptibility is relatively small, if any.
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PMID:[Immunogenetic analysis of rheumatoid arthritis in the Japanese population]. 851 35


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