THE ROLE OF THE SERUM IMMUNE-ADHERENCE INHIBITOR IN THE PATHOGENESIS OF MALARIA NEPHROPATHY

Abstract

The ability to participate In immune adherence is one biologic property of cells bearing, on their surfaces, the activated third complement component (C3b). Recently, it has been shown that human renal glomeruli, like some cells in the body, possess C3b receptors and that C3b-bearing cells can adhere unto these glomerular receptors. In some immune complex glomerular diseases, immune complexes and C3 have been demonstrated in the kidneys. Hence, the finding of C3b receptors in human renal glomeruli was thought to be significant in the deposition of immune complexes bearing complement in immune complex glomerulonephritis. But, there is a normal human serum protein capable of cleaving C3b into two fragments, thereby destroying its ability to participate in immune adherence. This protein is therefore thought to be the physiological factor which normally prevents the persistence of C3b-bearing complexes after deposition in the glomeruli. Thus, the level and degree of activity of this C3b inactivator may be equally significant in immune complex glomerular diseases. In other words, a deficiency of the inactivator could predispose to diseases such as childhood nephrosis. In Africa, nephrosis, especially in children, has been mainly associated with malaria, particularly quartan malaria. If indeed there is C3b inactivator deficiency in malarial nephrosis, could malaria parasites be involved in bringing about the deficiency? The C3b inactivator was tentatively described in this work as C3binase because its activity was reminiscent of an enzyme. Characterization of C3binase by gel chromatography, immunoelectrophoresis and other physico-chemical treatments, showed that it was similar, in the investigated properties, to the already described "conglutinogen - activating" factor, KAF (or C3bINA).

The serum C3binase levels of (87) childron and (28) adult nephrotics were determined and compared v/lth the levels in (318) apparently healthy individuals, (25) falciparum malaria children and other miscellaneous patients. The test system was the complement - coated sheep erythrocyte - rabbit antibody (EAC), with human group 0 erythrocytes as indicator cells. C3binase levels were significantly lower in nephrotics when compared with the other study groups. Furthermore, the results showed an acquired C3binase deficiency in malarial conditions generally and childhood nephrosis in particular.

The role of immunoconglutinins (antibodies to fixed C3 and C4) in preventing or potentiating glomerular injury, on the basis of its relationship to C3binase activity, could not be defined, since there was generally a negative correlation between the levels of the two factors. C3b receptors were demonstrable, by the technique used, in human renal glomeruli, but not in the cerebral and cerebellar cortices, the liver, the stomach pylorus, the placenta and the synovium. The degree of reversal of the adherence of immune complexes (EAC) unto renal glomeruli, effected by a serum sample, was found to be directly related to its C3binase level or activity. Thus, the acquired deficiency of C3binase found in malarial conditions and the observation that malarial pigment preparations inhibit C3binase activity, led to the conclusion that during malarial infections, malaria metabolic products may enhance the immunepathogenesis of malarial nephropathy by causing C3binase deficiency, thereby promoting the persistence of complement-bearing immune complexes in the glomeruli.