MLC-blocking factors in uremic sera.

Abstract

In 24 patients on regular hemodialysis, the sera were analyzed for the capacity to inhibit mixed lymphocyte culture (MLC) responsers in lymphocytes from healthy individuals. The sera from 15 of these patients (63%) inhibited MLC>50 per cent compared to control serum. Seven of the MLC blocking sera contained multispecific anti-HLA antibodies. The level of serum urea and serum creatinine was the same in sera with or without MLC inhibition. In two patients with MLC inhibiting sera but with no detectable cytotoxic anti-HLA antibodies, the plasma concentrations of middle molecules were high. The MLC inhibiting effect of anti-HLA antibodies was removed by repeated absorptions with platelets and lymphocytes. However, in sera containing "uremic" factors the MLC inhibiting effect was not removed by absorptions. Ultrafiltrate (cut-off point 50,000 daltons) from uremic plasma also gave inhibition of MLC responses compared to ultrafiltrate from normal plasma. Pooled ultrafiltrate from plasma with high concentrations of middle molecules gave the strongest inhibition. Thus, it is concluded that MLC inhibition in uremic sera is caused by anti-HLA-A, -B, -C, and HLA-DR antibodies and by ultrafiltrate of plasma most probably due to middle molecules.