Open AccessAnti‐idiotypic activity against anti‐myeloperoxidase antibodies in pooled human immunoglobulin
Author(s) -
PALL A. A.,
VARAGUNAM M.,
ADU D.,
SMITH N.,
RICHARDS N. T.,
TAYLOR C. M.,
MICHAEL J.
Publication year - 1994
Publication title -
clinical & experimental immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.329
H-Index - 135
eISSN - 1365-2249
pISSN - 0009-9104
DOI - 10.1111/j.1365-2249.1994.tb06520.x
Subject(s) - myeloperoxidase , antibody , chemistry , microbiology and biotechnology , affinity chromatography , sepharose , enzyme , biochemistry , immunology , biology , inflammation
SUMMARY We investigated the ability of six different pooled human immunoglobulin (PHIG) preparations to inhibit the binding of anti‐myeloperoxidase (MPO) antibodies to MPO. All six PHIG preparations inhibited the binding of anti‐MPO antibodies from six sera to MPO in a concentration‐dependent manner in the concentration range 0·016 10 mg/ml. There was considerable 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 maximum inhibition of 42%. Little inhibition was seen with F(ab′) 2 of normal human IgG from individual donors (1·‐12·2% al the maximum concentration of 2 mg/ml). F(ab′) 2 fragments from three anti‐MPO containing 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 fragments 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 antibodies. These observations indicate binding between the variable regions of PHIG and the antigen binding site of anti‐MPO antibodies, and are consistent with an anti‐idiotypic reaction. The variability seen in the inhibitory effect of the different PHIG preparations in anti‐MPO‐positive sera implies differences in their anti‐idiotype content, while the variability of the inhibitory effect of a particular PHIG preparation between different sera suggests heterogeneity in the idiotypic repertoire of anti‐MPO antibodies. Such variations in the inhibitory effect of different PHIG preparations on antibody binding may be an important determinant of their therapeutic effect.