GLOMERULAR DEPOSITION OF THE COMPLEMENT C4 ISOTYPES C4A AND C4B IN GLOMERULONEPHRITIS

Background. Complement C4 is a component of the classical complement p athway, which is a major mediator of inflammation in many forms of glo merulonephritis. The two isoforms of C4-C4A and C4B-differ in their ph ysicochemical and functional properties. Methods. The glomerular depos ition of C4A and C4B was investigated in 39 cases of glomerulonephriti s with classical pathway activation using isotype-specific monoclonal antibodies 99H7 (C4A) and 1288 (C4B) and indirect immunofluorescence. Complement C4 phenotypes of all patients were determined by agarose ge l electrophoresis and immunoprecipitation. Results. Three biopsies con tained only the isotype C4B. C4 phenotyping revealed complete C4A defi ciency in these three patients. Both isotypes C4A and C4B were detecte d in 36 biopsies. In 19 (53%) thereof staining for both isotypes was i dentical. In the remaining 17 (47%), staining intensity of C4A predomi nated over C4B. The distribution of these two staining patterns did no t differ between membranous glomerulonephritis and lupus nephritis. Th ey were also independent of C4A and C4B allotypes including the presen ce or absence of null alleles at either gene locus. In no case was C4B staining stronger than C4A staining. Serum creatinine and proteinuria did not differ between patients with identical and C4A-dominant C4 de position. Conclusion. The most likely but still hypothetical explanati on for predominance in glomerular deposition of C4A over C4B in many c ases of immune complex-mediated glomerulonephritis is the greater affi nity of C4A to protein-containing immune complexes as compared to C4B.