IMMUNOGENETIC STUDIES IN IDIOPATHIC NEPHR OTIC SYNDROME IN CHILDREN -CLINICAL IMPLICATION OF HLA TYPING

Background: Idiopathic nephrotic syndrome in children seems to have a genetic background. Familial cases and strong associations with certai n HLA antigens support this hypothesis. The aim of this study was to a nalyze, whether the difference in clinical courses of the disease is r eflected by differences in their HLA pattern. Methods: We performed se rological HLA typing (HLA-A, -B, -DR) in 347 children with nephrotic s yndrome. Furthermore, in 161 of these patients HLA class II antigens ( HLA-DRB, -DQB, -DQA) were studied by the method of restriction fragmen t length polymorphism. This method allows to differentiate class II an tigens more precisely. According to the response to corticosteroids, p atient groups were divided into steroid-sensitive and steroid-resistan t patients. The steroid-sensitive group was subdivided according to th e frequency of relapses. Results: In steroid-sensitive nephrotic syndr ome, we found a strong association with HLA-DR 7. Restriction fragment length polymorphism typing revealed, that this was due to its split D RB7.1. The frequencies of DQB2b and DQA3 were also increased in these patients. The relative risk for steroid-sensitive nephrotic syndrome w as markedly increased in DRB7.1/17.1 heterozygotes (relative risk = 16 .5 in German patients). The strongest association was found between fr equently relapsing nephrotic syndrome and DR3/7. After receiving alkyl ating agents, time until relapse was significantly short er in DR7-pos itive patients. After 3 years only 36% showed a stable remission vs 81 % of the DR7-negative patients. In steroid-resistant nephrotic syndrom e HLA antigen frequencies were not significantly different from contro ls. Conclusion: We conclude that 1) restriction fragment length polymo rphism typing reveals stronger associations between HLA class II antig ens and nephrotic syndrome than serological typing; 2) the presence or absence of certain HLA antigens may predict the clinical course in ne phrotic syndrome, e, g. DR3/DR7 heterozygous patients are at high risk for frequently relapsing nephrotic syndrome; 3) therapy with alkylati ng agents in frequently relapsing nephrotic syndrome is less effective in the presence of HLA-DR7.