Hypocomplementemia of membranoproliferative nephritis. Dependence of the nephritic factor reaction on properdin factor B.
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.
D000042:Absorption; D001797:Blood Protein Electrophoresis; D003165:Complement System Proteins / Q000378:metabolism*; D004591:Electrophoresis, Polyacrylamide Gel; D006358:Hot Temperature; D006801:Humans; D007122:Immunoelectrophoresis; D009393:Nephritis / Q000097:blood*; D011414:Properdin / Q000502:physiology*; D015054:Zymosan / Q000494:pharmacology
D011414:Properdin; D003165:Complement System Proteins; D015054:Zymosan