The influence of HLA-linked genes on the severity of anti-GBM antibody-mediated nephritis.

Thirty-nine Caucasian patients with glomerulonephritis caused by autoantibodies to glomerular basement membrane (GBM) were studied. They were segregated into three groups depending on presentation: Group 1 (19 patients) were anuric or oliguric, group 2 (13 patients) had rapidly deteriorating renal function but were not oliguric, and group 3 (seven patients) had stable renal function. The incidence of HLA-DR2 was greatly increased; it was present in 34 of 38 patients in whom DR antigens were identified compared to 43 of 154 controls (Pc = 0.63 X 10(-8), relative risk 36, etiological fraction 0.86). The incidence of HLA-B7 was also increased; present in 23 of 39 patients and 43 of 193 controls (Pc = 0.26 X 10(-4), relative risk 5.0, etiological fraction 0.43). These data were analyzed for a third order association between HLA-DR2, HLA-B7, and anti-GBM disease. Such an association was probable for patients in group 1 (P = 0.27 X 10(-6), likely for those in group 2 (P = 0.024) but unlikely for patients in group 3 (P = 0.62) suggesting HLA-B7-associated genes influence severity. Clinical results from a subset of the patients referred directly on presentation showed that patients who inherited HLA-B7 together with DR2 had significantly higher plasma creatinines, a greater proportion of glomeruli surrounded by crescents and a worse prognosis. Despite this there was little difference in severity of their lung disease.