Study on proteinase-inhibiting capacity of plasma alpha 2-macroglobulin in idiopathic nephrotic syndrome

We studied the relationship between plasma alpha 2-macroglobulin (alpha 2M) and depressed cell-mediated immunity in idiopathic nephrotic syndrome (INS). Plasma alpha 2M concentrations (mumol/l) were increased during relapses of INS; however, the proteinase inhibitory activity, measured using bacterial thermolysin, was significantly decreased when calculated per 1 mol of alpha 2M, implying a reduced proteinase-inhibiting capacity of alpha 2M. The decreased proteinase-inhibiting capacity of alpha 2M was associated with the inhibitory activity of plasma on normal lymphocyte blastogenesis. Purified alpha 2M, when complexed with chymotrypsin, intensively inhibited normal lymphocyte blastogenesis induced by concanavalin A, as compared with the free form of alpha 2M. From these results it is suggested that, although the amount of alpha 2M protein has increased in the plasma of INS patients during relapse, its binding capacity to proteinases has relatively decreased. The results of this study may provide speculation for both the well-known high plasma alpha 2M concentrations and the immunodepression, both of which have been observed in INS patients in the past few decades.