Inhibition of Human Eosinophil Chemotaxis by IgA Paraproteins

Sera from patients with IgA myeloma inhibit normal human eosinophil chemotaxis. No correlation was noted between inhibition and the absolute concentration of IgA or lambda-K light-chain type. Eosinophil chemotactic inhibitory activity was associated with isolated IgA paraproteins and was found to be cell directed and stable at 56 degrees C. Pepsin digestion of IgA paraproteins resulted in loss of both IgA Fc fragment and eosinophil chemotactic inhibitory activity. Polymeric IgA accounted for most of the inhibitory activity as evidenced by sucrose density gradient centrifugation studies and a loss of inhibitory activity following dithiothrietol reduction and iodoacetamide alkylation which converted polymeric IgA to monomeric IgA. Comparative studies with neutrophils showed that both neutrophil and eosinophil chemotaxis and chemokinesis were effectively inhibited by IgA paraproteins. The mechanisms of suppression of eosinophil and neutrophil chemotaxis by IgA paraproteins appear to be similar and possibly may involve a membrane receptor for IgA.