ANTIIDIOTYPIC ACTIVITY AGAINST ANTIMYELOPEROXIDASE ANTIBODIES IN POOLED HUMAN-IMMUNOGLOBULIN

We investigated the ability of six different pooled human immunoglobul in (PHIG) preparations to inhibit the binding of anti-myeloperoxidase (MPO) antibodies to MPO, All six PHIG preparations inhibited the bindi ng of anti-MPO antibodies from six sera to MPO in a concentration-depe ndent manner in the concentration range 0.016-10 mg/ml. There was cons iderable variation in the ability of each PHIG preparation to inhibit the binding of anti-MPO antibody in a given serum. Further differences were seen in the ability of a given PHIG to inhibit anti-MPO binding in different sera. F(ab')(2) fragments from two PHIG preparations also inhibited in a concentration-dependent manner anti-MPO binding to MPO in all six sera in the concentration range 0.002-2.65 mg/ml, with a m aximum inhibition of 42%. Little inhibition was seen with F(ab')(2) of normal human IgG from individual donors (18-12.2% at the maximum conc entration of 2 mg/ml). F(ab')(2) fragments from three anti-MPO contain ing sera and two affinity-purified anti-MPO antibodies were eluted by affinity chromatography from Sepharose-bound PHIG F(ab')(2) and showed anti-MPO antibody activity. We have shown that PHIG and F(ab')(2) fra gments of PHIG inhibit anti-MPO binding to MPO, and further that F(ab' )(2) fragments of PHIG bind to F(ab')(2) fragments of anti-MPO antibod ies. These observations indicate binding between the variable regions of PHIG and the antigen binding site of anti-MPO antibodies, and are c onsistent with an anti-idiotypic reaction. The variability seen in the inhibitory effect of the different PHIG preparations in anti-MPO-posi tive sera implies differences in their anti-idiotype content, while th e variability of the inhibitory effect of a particular PHIG preparatio n between different sera suggests heterogeneity in the idiotypic reper toire of anti-MPO antibodies. Such variations in the inhibitory effect of different PHIG preparations on antibody binding may be an importan t determinant of their therapeutic effect.