Isotype and affinity of anti-myeloperoxidase autoantibodies in systemic vasculitis

The role of immunoglobulin (Ig) isotype and affinity of antimyeloperoxidase (MPO) antibodies in the clinical expression of vasculitis (organ involvement, severity and evolution) remains incompletely defined. We have determined the anti-MPO antibody isotypes, as well as the apparent affinity constant (aK) of anti-MPO IgG by using fluid phase MPO inhibition of IgG binding in an MPO specific ELISA. Twenty-eight patients with anti-MPO antibodies and necrotic and crescentic glomerulonephritis, either isolated or associated to various other organ localizations, were analyzed. Serum samples were obtained before treatment and during follow-up. No association was observed between the isotype, the level or apparent affinity of anti-MPO antibodies and the clinical symptoms, severity, and organ distribution of vasculitis, including alveolar hemorrhage. No significant correlation was found between the apparent affinity and the level of anti-MPO IgG. However, the presence of anti-MPO IgM was clearly associated with low affinity anti-MPO IgG and vice versa. Furthermore, in a longitudinal study, high levels of anti-MPO IgM, when present, were observed early in the course of the disease and in some cases preceded the reappearance of anti-MPO IgG during relapses. High affinity anti-MPO IgG were usually present before treatment. Immunosuppressive therapy resulted in decreased apparent affinity and level of anti-MPO IgG. Importantly, anti-MPO IgG level increased during relapses but the affinity of these IgG autoantibodies remained low.(ABSTRACT TRUNCATED AT 250 WORDS)