Hypocomplementemia of membranoproliferative nephritis. Dependence of the nephritic factor reaction on properdin factor B

• Published in: The Journal of clinical investigation Vol. 52; no. 4; pp. 896 - 904
• Main Authors: Ruley, E J, Forristal, J, Davis, N C, Andres, C, West, C D
• Format: Journal Article
• Language: English
• Published: United States 01.04.1973
• Subjects: Absorption; Blood Protein Electrophoresis; Complement System Proteins - metabolism; Electrophoresis, Polyacrylamide Gel; Hot Temperature; Humans; Immunoelectrophoresis; Nephritis - blood; Properdin - physiology; Zymosan - pharmacology
• ISSN: 0021-9738
• DOI: 10.1172/JCI107254

Membranoproliferative nephritis in children is frequently associated with a hypocomplementemia produced at least in part by C3 breakdown mediated by a circulating anticomplementary factor known as C3 nephritic factor (C3NeF). C3 breakdown by this factor in vitro requires the presence of a pseudoglobulin cofactor and magnesium. The present study provides evidence that properdin factor B (C3 proactivator) is activated in the nephritic factor reaction and is the direct mediator of C3 breakdown by C3NeF. Depletion of factor B from mixtures of normal human serum (NHS) and plasma from a patient with membranoproliferative nephritis (MPP), either by heating or by immune equivalence absorption, blocks C3 breakdown by C3NeF. Addition of purified factor B to these mixtures restores the anticomplementary effect. When purified factor B is added to mixtures of MPP and purified C3, breakdown also occurs. Associated with the C3 breakdown is a change in the electrophoretic mobility of factor B from the beta to the gamma position, a shift which has been associated with cleavage activation of the molecule. Further, serum factor B levels are often low in patients with membranoproliferative nephritis and bear a rough inverse correlation with C3NeF levels. It thus appears that factor B is the previously described heat-labile C3NeF cofactor. Whether the C3NeF reaction proceeds via a pathway comparable to that activated by the cobra venom factor or via that activated by zymosan or inulin cannot be determined from the present data.