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)

One hundred and ten patients with rheumatoid arthritis (RA) were studied for a possible influence of HLA phenotypes on the reaction to parenteral gold in the first 6 months of treatment, in terms of both clinical response and toxicity. Frequencies of HLA-B8 and -DR3 were significantly increased in patients who responded excellently to gold treatment as compared with non-responders (p = 0.04 for both antigens). On the other hand, for HLA-DR7 there was a tendency for increased frequency in non-responders versus excellent and moderate responders (p less than 0.03; Pc = n.s.). Drug toxicity was higher in excellent than in non-responders (p less than 0.04), being exceptionally high in male excellent responders (85% versus 33% in females, p less than 0.01), probably due to the increased frequency in B8 and DR3 in the excellent responder group as a whole and in the excellent responder males in particular. We conclude that HLA antigens B8 and DR3 co-determine both toxicity and excellent clinical response to parenteral gold, whereas the presence of DR7 is possibly associated with non-response. In addition, we found sex differences in reaction to parenteral gold, which may be related to an increased frequency of HLA-B8 and -DR3 in male RA patients.
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PMID:The influence of HLA phenotypes on the response to parenteral gold in rheumatoid arthritis. 309 99

To clarify the natural course of gold nephropathy and thereby facilitate its clinical management 21 patients with rheumatoid arthritis who developed proteinuria during treatment with intramuscular sodium aurothiomalate were studied in detail throughout their renal illnesses. Renal biopsies were performed, and creatinine clearance and proteinuria were measured serially for 60 months (range 16-130 months). Ten patients developed proteinuria after six months' treatment, 15 after 12 months, and 18 after 24 months. When treatment was stopped the proteinuria reached a median peak of 2.1 g/day (range 0.7-30.7 g/day) at two months (range 1-13 months) before resolving spontaneously, in eight patients by six months, in 13 by 12 months, and in 18 by 24 months. All patients were free of proteinuria by 39 months, the median duration being 11 months. The median first and last measurements of creatinine clearance showed no significant change (77 ml/minute and 59 ml/minute, respectively), and no patient died from or needed treatment for renal failure. HLA-B8 or DR3 alloantigens, or both, were identified in seven patients. Renal biopsy specimens showed membranous glomerulonephritis in 15 patients, a minimal change nephropathy in two, mesangial electron dense deposits in two, and no appreciable glomerular changes in two. In these 21 patients the proteinuria of gold nephropathy resolved completely when treatment was withdrawn. Renal function did not deteriorate, corticosteroids were unnecessary, and several different renal lesions were seen.
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PMID:The natural course of gold nephropathy: long term study of 21 patients. 311 21

The association between HLA antigens and adverse drug reactions (ADR), (e.g. proteinuria, haematological abnormalities, stomatitis, diarrhoea and dermatitis) in rheumatoid arthritis (RA) to sodium aurothiomalate (gold) and to D-penicillamine (PA) were studied in 32 patients. Thirty-eight RA patients treated with gold and PA, and with no ADR to these drugs, were used as controls. The frequency of HLA B8 was significantly (p less than 0.05) increased among RA patients with ADR compared to plasma donors. DR3 was also significantly increased (p less than 0.05) in RA patients with haematological ADR compared to plasma donors. Haematological ADR occurred significantly (p less than 0.05) more often in DR3 positive patients (55%) than among DR3 negative RA patients (27%).
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PMID:HLA antigens and adverse drug reactions to sodium aurothiomalate and D-penicillamine in patients with rheumatoid arthritis. 315 29

A 61-year-old woman, suffering from classic seropositive rheumatoid arthritis with rheumatoid nodule histologically documented, developed temporal arteritis. HLA-DR typing revealed the presence of DR3 and DR4 antigens. The findings from previous studies support the association of HLA-DR antigens, giant cell arteritis-polymyalgia rheumatica and rheumatoid arthritis, and suggest the participation of a common immunogenetic mechanism in their pathogenesis.
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PMID:Temporal arteritis in seropositive rheumatoid arthritis with rheumatoid nodule. 318 May 40

Seventy-two patients with rheumatoid arthritis (RA) and 18 with systemic lupus erythematosus (SLE) were typed for HLA class I and II antigens. No association was found with any of the antigens tested. However, B8 and DR3 were increased in patients with extraarticular features (EAF), while DR1 was increased in those with RA without EAF. In SLE a trend towards an increased frequency of DR7 was observed. DR5 was the negative marker in both diseases. Our results confirm the peculiar genetic characteristics in our population.
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PMID:Association between DR antigens, rheumatoid arthritis with and without extraarticular features and systemic lupus erythematosus in northern Italy. 325 84

A patient is described who had insulin-dependent diabetes mellitus for 2 years, prior to developing rheumatoid arthritis and then subsequently ankylosing spondylitis and dermatomyositis. Diagnostic criteria for all diseases are fulfilled. HLA typing revealed the presence of HLA A2, A9, B8, B27, DR3 and DR4 antigens. The concomitant coexistence of diabetes mellitus, rheumatoid arthritis, ankylosing spondylitis and dermatomyositis appears to have occurred in an individual genetically susceptible to these diseases.
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PMID:Coexistence of rheumatoid arthritis, ankylosing spondylitis and dermatomyositis in a patient with diabetes mellitus and the associated linked HLA antigens. 336 34

To assess therapeutic effect and toxicity of D-penicillamine in relation to HLA antigens, 111 consecutive patients with rheumatoid arthritis (RA) were followed for a period of 7-9 years. Side effects occurred in 60% and were the main reason for withdrawal in 52%. HLA typing was performed in 86; overall frequencies were comparable with those found in other studies in patients with RA. Drug induced proteinuria (5 patients) was associated with HLA-B8/DR3 (60 vs 9%), and thrombocytopenia (23 patients) with HLA-DR4 (94 vs 67%). Therapeutic effect was good in 26 (23%), and moderate in 30 (27%). No single variable, including HLA antigens, was predictive of effectiveness. It is concluded that although some of the side effects were associated with HLA antigens, HLA typing is not useful in predicting the outcome of treatment with D-penicillamine.
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PMID:Longterm followup of treatment with D-penicillamine for rheumatoid arthritis: effectivity and toxicity in relation to HLA antigens. 343 18

To investigate the possible coinheritance of autoimmune diseases that are associated with the same HLA antigen, we studied 70 families in which at least two siblings had either type I diabetes mellitus (IDDM), autoimmune thyroid disease (ATD), rheumatoid arthritis (RA), or a combination of these diseases. HLA-A, B, and C typing was performed on all affected sibs in one generation or more. First, we estimated by sib-pair analysis the disease allele frequency (pD) and the mode of inheritance for each disease. According to the method of ascertainment entered into the analysis, the pD for ATD ranged from .120 to .180, for an additive (dominant) mode of inheritance. For RA, the pD ranged from .254 to .341, also for additive inheritance, although recessive inheritance could not be excluded. For IDDM, the pD ranged from .336 to .337 for recessive inheritance; additive inheritance was rejected. Second, we examined the distribution of shared parental haplotypes in pairs of siblings that were discordant for their autoimmune diseases. The results suggested that the same haplotype may predispose to both IDDM and ATD, or IDDM and RA, but not to both RA and ATD. Analysis of pedigrees supported this hypothesis. In 16 families typed for HLA-DR also, the haplotype predisposing to both IDDM and ATD was assigned from pedigree information to DR3 (44%), DR4 (39%), or DR5, DR6, or DR7 (5.5% each). In some families, these haplotypes segregated over several generations with ATD only (either clinical or subclinical), suggesting that in such families, ATD was a marker for a susceptibility to IDDM. In several families, an IDDM haplotype segregated with RA but not with ATD. This suggests that ATD- and RA-associated susceptibilities to IDDM may be biologically different and thus independently increase the risk of IDDM.
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PMID:Genetic interrelationship between insulin-dependent diabetes mellitus, the autoimmune thyroid diseases, and rheumatoid arthritis. 345 97

In a 3-centre study involving 144 patients with rheumatoid arthritis (RA), a relationship between side effects from D-penicillamine and HLA antigens, allotypic markers of the IgG heavy chain (Gm) and allotypes of complement components Bf, C4A and C4B was sought. There was a significant association between proteinuria induced by D-penicillamine and the antigens DR3 and B8. However, the presence of DR2 seemed to protect against the development of proteinuria. Thrombocytopenia from D-penicillamine was significantly associated with HLA-A1 and DR4; 15 of 23 patients who possessed both antigens developed thrombocytopenia (p less than 0.001 uncorrected, approximate relative risk (RR) = 5.5). A null complement allele located at the C4B locus (C4BQO) was also associated with thrombocytopenia from D-penicillamine (p less than 0.005, RR = 17.3). Our study confirms the findings from other series which indicate that there is a genetic predisposition for the development of proteinuria from D-penicillamine in RA and suggests that this may also be the case in D-penicillamine induced thrombocytopenia.
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PMID:Genetic markers in rheumatoid arthritis relationship to toxicity from D-penicillamine. 345 89

Forty-eight Canadian patients with rheumatoid arthritis (RA) were tissue typed for class 1 (HLA-A, B, and C) and class 2 (HLA-DR and DQ) antigens in an attempt to identify HLA associations and to relate them to disease manifestations and drug toxicity. HLA-DR4 was found with a significantly higher frequency among patients with RA than in the control population. DR4 correlated with presence of rheumatoid nodules and pulmonary manifestations, and was more frequent among patients who had vasculitis. All 4 patients who died were DR4 positive. DR2 and DR7 were less frequent in our patients. There was no association between the presence of DR3 or DR4 and drug toxicity.
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PMID:HLA and disease manifestations in rheumatoid arthritis--a Canadian experience. 345 90


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