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)

Rheumatoid arthritis (RA) is associated with the presence of particular HLA-DRB1 alleles. In order to characterize HLA-DQB1 and/or-DPB1 alleles that contribute to disease susceptibility besides HLA-DRB1 alleles, we have analysed the HLA-DRB1, -DQB1 and -DPB1 polymorphism in 84 RA patients and 135 controls. HLA typing for HLA-DRB1 and -DQB1 alleles was performed using sequence-specific primers in combination with sequence-based typing. HLA-DPB1 alleles were characterized by reverse dot-blot hybridization. Our data confirm the predominant role of the (Q)R/KRAA sequence from AA position 70-74 of the HLA-DRB chain for disease susceptibility. In particular, the lysine (K) substitution at position 71 was highly significantly associated with RA. Analysis of the DQB1 locus revealed no association with RA when linkage disequilibrium between HLA-DRB1 and -DQB1 alleles was considered. In contrast, we observed an increased frequency of HLA-DPB1*0401 among (Q)R/KRAA-positive patients. (Q)R/KRAA-negative RA patients exhibited an overrepresentation of HLA-DPB1*0201 and HLA-DPB1*0601. Rheumatoid factor (RF) production correlated with the presence of the disease-associated (Q)R/KRAA amino acid cassette of the HLA-DRB chain. When HLA-DPB1 allele frequencies were compared between RF-positive and RF-negative RA patients, we observed an increased frequency of HLA-DPB1*0401 among RF-positive RA patients and HLA-DPB1*0201 among RF-negative patients. These results suggest that besides the predominent role of HLA-DR molecules in RA, HLA-DP molecules may have an influence on disease susceptibility and could modulate disease progression. HLA-DPB1*0401 may function in addition to HLA-DRB1*04, whereas HLA-DPB1*0201 and -DPB1*0601 may represent additional risk factors among (Q)R/KRAA-negative RA patients.
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PMID:HLA-DR/DQ/DP interactions in rheumatoid arthritis. 944 4

To assess the association between HLA-DRB1 and elderly-onset rheumatoid arthritis (RA) (EORA) in Japanese people, we analysed the HLA-DRB1 antigen frequencies of EORA patients. The age at onset distribution of 852 Japanese RA patients was analysed, and EORA was defined as an age at onset of 60 yr or older. Among the 852 RA patients, 120 (14.1%) were EORA patients. Their HLA-DRB1 antigen frequencies were assessed for significant deviation from those of the control (n = 652) and adult-onset RA (AORA; disease onset between 16 and 59 yr; n = 732) groups. The Japanese EORA patients were positively associated with DRB1*0101, *0405 and *1502, and the relative risks were 2.7, 1.9 and 2.2, respectively. The frequency of DRB1*1502 was also significantly higher among the EORA patients than in the AORA patients. The EORA patients showed different trends from the AORA patients in their frequency of HLA-DRB1 alleles, which suggests that EORA may be a different subset from AORA in light of its immunogenetic background.
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PMID:Elderly-onset rheumatoid arthritis and its association with HLA-DRB1 alleles in Japanese. 948 58

Rheumatoid arthritis is the more frequent chronic inflammatory arthritis. It is a potentially severe disease which causes a functional handicap in nearly half the patients 10 years after the first clinical symptoms. However rheumatoid arthritis is a heterogenous disorder and no prognostic factors are universally accepted and validated. Clinical and biological data collected to date have provided a limited amount of information. Nevertheless, erythrocyte sedimentation rate, C reactive protein and rheumatoid factor titer appeared to be the more powerful available indicators or prognosis at the early stage of the disease. Recent studies strongly suggests that some autoantibodies and mainly genetic markers (HLA-DRB1 alleles) could be correlated with disease severity. Consequently, it would appear possible to distinguish immunogenetically homogeneous subpopulations of patients with rheumatoid arthritis. Serum concentrations of specific cartilage and bone molecules reflecting tissue turnover and metalloproteinases could correlate to rate of joint destruction. Finally a combination of the most pertinent markers could determine a "score of severity" of the disease.
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PMID:[Course, follow-up and prognosis of rheumatoid polyarthritis]. 950 19

The purpose of this study was to identify Vbeta gene families that are associated with rheumatoid arthritis (RA). A PCR-based assay was used to compare the Vbeta repertoire of unstimulated PBMC from 18 RA patients and 18 matched controls. The influence of an HLA-DRB1-binding peptide (HA307-319) on the Vbeta repertoire of PBMC in culture was compared in 11 RA patients and 10 controls. There was a larger variance in the percentage of BV14S1 transcripts in unstimulated PBMC from RA patients than from controls (p = 0.0003). The mean percentage of BV14S1 transcripts was higher in RA patients when prednisone-treated RA patients were excluded from the analysis (p = 0.0006). In vitro stimulation with the HA307-319 peptide increased the percentage of BV14S1 transcripts in PBMC from RA patients (+ 1.5 +/- 0.4%, p < 0.005) but not controls (+ 0.3 +/- 0.2%, ns), and the difference between RA patients and controls was significant (p = 0.03). In conclusion, there is an association between RA and the BV14S1 gene family in New Zealand patients.
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PMID:TCRBV14S1 and rheumatoid arthritis revisited: abnormalities in the percentage of transcribed TCRBV14S1 family genes in PBMC from rheumatoid arthritis patients. 950 81

The immune system is still regarded by many as autonomous, and prolactin (Prl) has traditionally been considered as a lactogenic hormone. Over the last 10 years, the total number of publications considering Prl is decreasing, while the number of those investigating its role in immunity sustainly increased. In addition to the pituitary gland, Prl-like peptides can be produced by activated leukocytes and fibroblasts. Elevated serum levels of Prl in (rat) adjuvant arthritis, (murine) collagen type II-induced arthritis, (murine and human) systemic lupus erythematosus (SLE), and (murine and rat) autoimmune type I diabetes may influence the outcome of the disease. It is suggested that mild hyperprolactinemia is a risk factor for the development of autoimmunity. This can occur under certain circumstances, for example adrenocortical deficiency or postpartum. In human SLE, Prl appears to favor the production of anti-double stranded DNA. While glucocorticoids would damp the immune reactivity, Prl constitutes a stimulatory link between the neuroendocrine and immune systems. Future directions should include: 1) multicenter projects for evaluation of the therapy with Prl-inhibiting compounds in SLE, considering for example the HLA-DRB1 *0301 status; and 2) the regulation of extra-pituitary Prl-like cytokines ("proliferins") (e.g., in rheumatoid arthritis synovium) and their role in the production of catabolic enzymes.
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PMID:Prolactin in autoimmune diseases. 952 Oct 87

Multiple HLA-DRB1 alleles encoding a shared epitope (SE) at amino acid positions 70-74 are associated with susceptibility and severity of rheumatoid arthritis (RA). We examined the relationship between the number and DRB1 genotype of SE alleles inherited and long-term outcomes of 180 community-based, Caucasian female RA patients followed annually for up to 12 years. Outcomes examined were physician assessment of RA course; annual measures of pain, function, and number of painful joint groups; history of joint surgery; and resource utilization. Models accounted for correlation among serial observations for the same patient and adjusted for patient age and disease stage. We examined two genetic models: a SE model in which patients were classified according to the number of SE copies inherited and a genotype model in which patients were categorized into one of six groups based on the inherited DRB1 genotype. We used likelihood ratio tests to compare these genetic models and to compare alternative model specifications. Our results demonstrate strong associations between inheritance of the SE and long-term outcomes of community-based Caucasian females with RA. However, the pattern of results is not consistent across the outcomes. An additive model of risk is apparent for history of joint surgery and RA hospitalization. In contrast, a near reversal of this pattern is apparent for function, joint pain, pain rating, and RA physician visits. Finally, although the genotype model did not appear to be a better predictive model for RA outcomes overall, it did reveal some striking heterogeneity of SE alleles that was masked by the more parsimonious SE model. For example, the odds ratio (OR) for joint surgery for patients with 2 SE copies (OR = 3.16) reflects an average of 2 very different ORs when patients are further categorized according to genotype groups 4 and 5 (OR = 1.3 and 11.9, respectively).
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PMID:Inheritance of the shared epitope and long-term outcomes of rheumatoid arthritis among community-based Caucasian females. 952 11

Susceptibility to develop Rheumatoid arthritis (RA) maps to a highly conserved amino acid motif ("the shared epitope") expressed in the third hypervariable region of different HLA-DRB1 alleles. This motif, namely QKRAA, QRRAA or RRRAA helps the development of RA by an unknown mechanism. However, it is now established that the shared epitope can 1. Shape the T cell repertoire. 2. Interact with 70 kD heat shock proteins.
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PMID:HLA-DR and the development of rheumatoid arthritis. 954 14

Multiple HLA-DRB1 alleles encoding a shared epitope (SE) at amino acid positions 70-74 are associated with susceptibility to rheumatoid arthritis (RA). However, the nature of the association and the mode of inheritance differ depending upon the source of RA patients and laboratory methodology. We studied the relative predispositional effects (RPE) and mode of inheritance of DRB1 alleles among a community-based sample of 180 RA patients and 116 healthy controls, all Caucasian females. Polymerase chain reaction (PCR)-based assays were used for DRB1 genotyping, and the genotypic distributions were analyzed by both the RPE and antigen genotype frequency among patients (AGFAP) methods. We examined the evidence of synergy among DRB1 alleles for RA risk by comparing the observed DRB1 genotype distribution to that predicted under Hardy-Weinberg equilibrium. Fifty-six percent of RA cases were attributable to DRB1 alleles encoding the SE. The RPEs of DRB1 alleles were *0401 > *0404 > *1001 > *0408 > *0101. The strength of the RA association was not significantly different for these alleles. The AGFAP analysis was consistent with a recessive mode of inheritance for DRB alleles, while an additive (dominant) model was rejected. We found no evidence of synergy for RA risk among individual DRB1 alleles based on comparison of the observed vs. predicted genotype distributions. These results suggest that among community-based Caucasian females with RA, the DRB1 RA susceptibility gene influences disease risk in a recessive fashion without synergy among individual DRB1 alleles.
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PMID:Relative predispositional effects and mode of inheritance of HLA-DRB1 alleles among community-based Caucasian females with rheumatoid arthritis. 955 51

The aim of the study was to evaluate the relationship between the presence of the 'rheumatoid epitope', defined by a sequence motif in the HLA-DRB1 alleles, rheumatoid factor and disease severity in Northern Italian patients with rheumatoid arthritis (RA). Twenty-nine DR4-positive and 57 DR4-negative RA patients were studied. Each DR4-positive patient was matched with two DR4-negative controls of similar disease duration and sex. HLA-DRB1 alleles were determined in the 86 patients and 351 controls from the same geographical area. The patients were retrospectively evaluated for extra-articular features (EAF) and radiographic damage. The rheumatoid epitope was expressed in 45% of patients. No significant differences in the presence of rheumatoid factor, EAF and articular damage were observed between patients with no, one or two doses of epitope. However, the patients encoding the epitope by an HLA-DR4 allele had a higher number of eroded joints and a higher Larsen score compared to those without the epitope. No differences were present between patients expressing HLA-DRB1*01 alleles and those lacking the rheumatoid epitope. Even in the absence of expression of the rheumatoid epitope, seropositive patients had more EAF and more erosive disease compared to those who were seronegative. Even if most Northern Italian RA patients do not express the rheumatoid epitope, the radiological severity of disease is associated with HLA-DRB1*04 alleles.
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PMID:HLA-DRB1 alleles associated with rheumatoid arthritis in Northern Italy: correlation with disease severity. 956 71

To assess the association between HLA-DRB1 alleles and shoulder destruction due to rheumatoid arthritis (RA) in Japanese, we typed for HLA-DRB1 alleles in 100 Japanese RA patients who could be classified into 5 groups: non-progressive (N) with normal radiographs; erosive (E) showing marginal erosion but no collapse; collapse (C) showing subchondral cysts followed by collapse; arthrosis-like (A) showing osteoarthrotic features; and the mutilating (M) showing mutilating bone destruction. The HLA-DRB1*0405 antigen frequency in N, E, C, A, and M types was 55%, 61%, 33%, 71%, 100%, respectively. That in the M type (100%) was significantly higher than that in the others (the N, E, C, and A types; 57%). These findings suggest that the most severe shoulder joint destruction pattern in RA, the M type, is associated with HLA-DRB1*0405.
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PMID:An association between the natural course of shoulder joint destruction in rheumatoid arthritis and HLA-DRB1*0405 in Japanese patients. 957 42


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