Biomedical subjects
Publications and source records attributed to P Dyer.
The haplotype sharing distribution in affected sib pairs are used to demonstrate the linkage of a susceptibility gene for rheumatoid arthritis (RA) to the HLA region. Family and population studies suggest heterogeneity in the etiology of RA.
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Properdin factor B (Bf) phenotyping was carried out in 392 patients with rheumatoid arthritis (RA) and in 360 controls. In RA there were increased frequencies of both the Bf*S gene (83 vs 78%; pc = 0.0003) and the BfSS genotype 73 vs 61%; pc = 0.0002) and reduced frequencies of the Bf*F1 gene (0.5 vs 2.2%; pc = 0.03) and the BfFS genotype (20 vs 29%; pc = 0.0007). The frequencies of Bf*S in DR4 positive and DR4 negative RA were similar so that the findings were not accounted for by linkage disequilibrium between DR4 and Bf*S.
We have studied HLA haplotypes, autoimmune diseases and circulating autoantibodies in 23 families with multiple cases of rheumatoid arthritis; 76 per cent of rheumatoid arthritis and 70 per cent of non-rheumatoid individuals were positive for HLA-DR4. The haplotypes Bw44-Bf*S-DR4; B40-Bf*S-DR4; and B15-Bf*S-DR4 were found in 13, 9 and 7 per cent of probands respectively and the B15-Bf*S-DR4 haplotype was found between four and five times more frequently in DR4-positive rheumatoid arthritis than in DR4 positive, non-rheumatoid arthritis families. Rheumatoid arthritis segregated with a DR4 positive haplotype in 13 families and with a DR4 negative haplotype in seven. Analysis of HLA haplotype sharing showed greater than random sharing by affected siblings which is in keeping with genes within the MHS influencing susceptibility to rheumatoid arthritis. Autoimmune thyroid disorders were seen in 8 per cent of family members investigated. They were significantly more frequent in those families in which rheumatoid arthritis segregated with a non-DR4 bearing HLA haplotype. This suggests that genes for autoimmune thyroid disease might predispose to rheumatoid arthritis independently of DR4. These genes are probably not HLA-linked, as there was no trend for HLA haplotype sharing to be increased in sibling pairs with either rheumatoid arthritis and thyroid disease or rheumatoid arthritis and thyroid autoantibodies respectively.
A controlled trial was carried out to assess the value of intensive plasma exchange in 27 renal transplant recipients with clinical and histological evidence of acute vascular rejection. In addition to standard immunosuppression, 13 patients received plasma exchange on six consecutive days at a mean exchange volume of 40.6 ml/kg of body weight each day using an intermittent cell separator. A further 14 patients received standard immunosuppression only. In addition, 10 patients exchanged prior to the controlled trial have been studied. Analysis of short-term benefit, as evidenced by a reduction in serum creatinine, and by subsequent graft survival revealed no significant difference in these parameters between the two groups in the controlled trial. This regimen of plasma exchange has not, therefore, been shown to modify acute renal allograft rejection.
In a series of 60 patients with idiopathic membranous nephropathy (IMN), 8 subjects, aged 16-65 years at presentation, suffered spontaneous relapse of proteinuria after remissions of 25 months to 30 years. Renal biopsy was performed at the time of relapse in 5 cases and revealed histopathology identical to that of the original lesion. Eight courses of immunosuppressive therapy given to 6 patients did not affect either the appearance or duration of remission or relapse. No patient had a familial tendency to renal disease. Immunogenetic markers, HLA A, B and DR, did not distinguish those who relapsed from other patients with IMN. At the end of the study, 3 patients were in a second remission, one had died of myocardial infarction during relapse, 3 remained nephrotic and one had mild renal insufficiency but no proteinuria. As compared with the rest of the series the overall prognosis was not influenced by the relapses.
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