Association of membranous nephropathy with T-cell receptor constant beta chain and immunoglobulin heavy chain switch region polymorphisms.
We have investigated T-cell antigen receptor constant beta chain genes (Tcr C beta) 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 beta probe in conjunction with the restriction endonuclease Bgl 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 mu heavy chain gene (S mu), 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.
D005796:Genes; D005803:Genes, Immunoglobulin; D005921:Glomerulonephritis / Q000235:genetics / Q000276:immunology*; D006684:HLA-DR Antigens / Q000235:genetics; D006801:Humans; D007143:Immunoglobulin Heavy Chains / Q000235:genetics*; D046911:Macromolecular Substances; D008285:Major Histocompatibility Complex; D011110:Polymorphism, Genetic; D012150:Polymorphism, Restriction Fragment Length; D011948:Receptors, Antigen, T-Cell / Q000235:genetics*; D012016:Reference Values
D006684:HLA-DR Antigens; D007143:Immunoglobulin Heavy Chains; D046911:Macromolecular Substances; D011948:Receptors, Antigen, T-Cell