Nephritogenic lambda light chain dimer: a unique human miniautoantibody against complement factor H.

摘要: A unique monoclonal Ig lambda light chain dimer (protein LOI) was isolated from the serum and urine of a patient with hypocomplementemic membranoproliferative glomerulonephritis. In vitro efficiently activated alternative pathway complement (AP). When added to normal human serum, LOI temporarily enhanced AP hemolytic activity, but during prolonged incubation activity depleted. Protein found bind factor H, main regulator molecule AP. By binding short consensus repeat domain 3 blocked one three interaction sites between H C3b thus inhibited induced an uncontrolled activation Structural analysis showed that belonged Vlambda3a subgroup chains. The variable (V) region most closely related predicted product Vlambda3 germline gene Iglv3s2, although it contained several residues in tertiary homology model structure form unusual ring charged around hydrophobic groove putative Ag site. This site fitted considerably well molecular containing reciprocal amino acids area. Apparently, functional blocking by Ab fragment-like had initiated development severe Thus, represents first described pathogenic miniautoantibody disease.