MYOPATHY AND PARAPROTEINEMIA WITH SERUM IGM BINDING TO A HIGH-MOLECULAR-WEIGHT MUSCLE-FIBER SURFACE PROTEIN

We evaluated a 69-year-old man with Waldenstrom's macroglobulinemia (I gM-kappa M-protein) and progressive weakness over 2 to 3 years. The ne urological examination showed symmetrical, predominantly proximal weak ness. Electrophysiological testing revealed small brief motor unit pot entials with fibrillations and positive sharp waves consistent with an irritative myopathy. The muscle biopsy specimen showed myopathic chan ges including variation in fiber size and increased connective tissue but no inflammation. IgM-kappa but not IgM-lambda was deposited along the surface of muscle fiber membranes. Serum IgM-kappa but not IgM-lam bda from the patient stained the surface of normal human muscle fibers but not other regions of muscle fibers or other tissues. The serum Ig M-kappa at dilutions up to 1:512,000 bound to a high-molecular-weight muscle protein by Western and dot blot studies. By enzyme-linked immun osorbent assay and Western blot analysis, serum IgM-kappa bound specif ically to the muscle protein and not to other muscle or neural antigen s, including GM(1) ganglioside, myelin-associated glycoprotein, and su lfatide. We conclude that the myopathy in our patient is probably rela ted to the presence of serum IgM-kappa antibodies directed against a m uscle surface antigen. Characterization of the target antigen, a high- molecular-weight protein located specifically in muscle, should furthe r elucidate the pathogenesis of this presumably humorally mediated imm une myopathy.