Complexes of α 1-microglobulin and monomeric IgA in multiple myeloma and normal human sera

Abstract

α 1-Microglobulin (α 1m), a glycoprotein heterogeneous in charge, was reported to occur both as a 31-kilodalton (kd) monomer [low mol. wt α 1m (LMW-α 1m)] and as polymers or complexes formed with other plasma proteins including IgA [high mol. wt α 1m (HMW-α 1m)]. The present study was designed to characterize HMW-α lm in normal human serum and in myeloma sera. The following sera were selected: five IgG, 16 IgA and four Bence-Jones protein myelomas, α 1m was identified by specific monoclonal antibodies in competitive radioimmunoassay and solid-phase ELISA. HMW-α 1m was found to be associated almost exclusively with monomeric IgA and possibly in very small proportion with dimeric IgA. Even in cases of predominantly dimeric IgA myelomas, α 1m was associated with the monomeric form of the monoclonal IgA. The molar ratio of HMW-α 1m to monomeric IgA never exceeded 3.5% and it was estimated to range from 0.5 to 1.4% in normal serum. No association with other proteins than IgA and no α 1m polymers were found in IgA myeloma. Two types of HMW-α 1m-IgA complexes were found: (a) those that were dissociable into IgA and LMW-α 1m after mild reduction, and (b) those which were dissociated only after complete reduction of the complexes into IgA and an 88-90-kd component bearing α 1m but no IgA epitopes. It was concluded that either of the two molecular species of α 1m bearing common epitopes, with apparent mol. wts of 31,000 and 88,000–90,000, respectively, could form stable complexes with monomeric IgA. The association is likely to be performed through disulfide bridges. Nearly all the 88–90-kd but only a small proportion of the 31-kd component is associated with IgA.