Association of membranous nephropathy with T-cell receptor constant ? chain and immunoglobulin heavy chain switch region polymorphisms

Abstract

We have investigated T-cell antigen receptor constant β chain genes (Tcr C _β) and immunoglobulin (Ig) heavy chain switch region genes of HLA-DR-typed patients with membranous nephropathy (MN) employing DNA restriction fragment length polymorphism (RFLP) analysis. When a Tcr C _β probe in conjunction with the restriction endonuclease BgI II was used, a significant increase in the frequency of a 10.0;9.2 kb heterozygous RFLP phenotype was found in MN (75.0 % versus 42.1 in controls; P=0.002). When Sst I-restricted DNA from MN patients was hybridized with a DNA probe homologous to the switch region flanking the Ig C _µ heavy chain gene (S _µ), there was a significant decrease in the frequency of the 2.1; 2.6 kb heterozygous RFLP phenotype in MN (24.0% versus 54.6% in controls; P=0.004). These results suggest that Tcr beta and Ig heavy chain loci, as well as HLA antigens, may be important in the pathogenesis of MN.