Aa. Pall et al., ANTIIDIOTYPIC ACTIVITY AGAINST ANTIMYELOPEROXIDASE ANTIBODIES IN POOLED HUMAN-IMMUNOGLOBULIN, Clinical and experimental immunology, 95(2), 1994, pp. 257-262
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.