Immunopathogenetic Role Of The M‐Protein In Neuropathy Associated With IgA Monoclonal Gammopathy

Abstract

Neuropathy has been reported in some patients with IgA monoclonal gammopathy of undetermined significance (MGUS) but the clinical and pathogenetic relevance of this association remains unclear. This is because the clinical and electrophysiological features of the neuropathy in reported patients were quite heterogeneous and only occasionally endoneurial deposits or anti‐neural reactivity of IgA M‐proteins were found. In order to clarify the possible role of IgA M‐proteins in the neuropathy we studied their reactivity with nerve antigens in 12 patients with neuropathy associated with IgA MGUS and in 15 patients with IgA MGUS without clinical or electrophysiological evidence of neuropathy. Patients' sera were tested for IgA reactivity with the glycolipids GM1, GM2, GD1a, GD1b, GQ1b and sulfatides by ELISA and with central (CNS) and peripheral nervous system (PNS) myelin and whole nerve homogenates by Western Blot. No IgA reactivity with any of the gangliosides tested or sulfatide was detected by ELISA in patients with neuropathy and IgA MGUS. By Western blot only one neuropathy patient had an intense IgA reactivity with several protein bands of the molecular weight (MW) of 80 to 200 kD, including high MW neurofilaments. A similar though less intense IgA reactivity with the same bands was detected in one patient without neuropathy. No other reactivity with neural proteins was detected in patients' sera more frequently or more intensely than in controls. The clinical features of the neuropathy in the four patients whose clinical reports were available showed an usually mild, predominantly motor (2) or sensory (1) or mixed (1) impairment, while electrophysiological studies showed a predominant axonal (2), demyelinating (1) or mixed (1) neuropathy. In the only patient in whom sural nerve biopsy was performed no endoneurial deposits of IgA were found. The heterogeneity of the clinical and electrophysiological findings in these patients together with the lack of a consistent pattern of IgA reactivity with neural antigens in the 12 patients examined fail to support, at least in these patients, a possible immunopathogenetic role of the IgA M‐proteins in the neuropathy.