title: Anti-idiotypic activity against anti-myeloperoxidase antibodies in pooled human immunoglobulin.
abstract: 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 (1.8-12.2% at 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.
authors.affiliation: Renal Research Laboratory, Queen Elizabeth Hospital, Edgbaston, Birmingham, UK.
authors.forename: A A
authors.initials: AA
authors.lastname: Pall
authors.forename: M
authors.initials: M
authors.lastname: Varagunam
authors.forename: D
authors.initials: D
authors.lastname: Adu
authors.forename: N
authors.initials: N
authors.lastname: Smith
authors.forename: N T
authors.initials: NT
authors.lastname: Richards
authors.forename: C M
authors.initials: CM
authors.lastname: Taylor
authors.forename: J
authors.initials: J
authors.lastname: Michael
mesh_terms: D000818:Animals; D000888:Antibodies, Anti-Idiotypic / Q000032:analysis*; D019268:Antibodies, Antineutrophil Cytoplasmic; D001323:Autoantibodies / Q000276:immunology; D002846:Chromatography, Affinity; D006801:Humans; D007140:Immunoglobulin Fab Fragments / Q000276:immunology; D007074:Immunoglobulin G / Q000276:immunology; D007136:Immunoglobulins / Q000276:immunology*; D051379:Mice; D009195:Peroxidase / Q000276:immunology*
chemical_list: D000888:Antibodies, Anti-Idiotypic; D019268:Antibodies, Antineutrophil Cytoplasmic; D001323:Autoantibodies; D007140:Immunoglobulin Fab Fragments; D007074:Immunoglobulin G; D007136:Immunoglobulins; D009195:Peroxidase