IgM Monoclonal Gammopathy-associated Neuropathies with Different IgM Specificity

Background And Purpose:   Antibodies directed against myelin-associated glycoprotein (MAG) are believed to be the most frequent biologic marker of the neuropathies associated with IgM monoclonal gammopathy of undetermined significance (MGUS). The objective of this study was to examine the prevalence of antiganglioside and/or sulfatide-positive patients and their clinical findings, including therapeutic response, compared to anti-MAG-positive or seronegative patients.

Methods:   We prospectively followed 46 patients with MGUS who were diagnosed in our tertiary referral centers for polyneuropathy since 1997. All patients underwent nerve conduction studies and were tested for anti-MAG, gangliosides, and sulfatide antibodies. All the anagraphic and clinical data (including symptoms, disability scale, therapy, secondary malignancy development) were recorded in a database and compared between three patients' groups (anti-MAG-positive; antiganglioside/sulfatide-positive; no reactivity).

Results:   Anti-MAG reactivity was present in 17 (37%) patients; other 17 patients (37%) had antiganglioside/sulfatide reactivity and 12 (26%) had no reactivity. Patients with antiganglioside/sulfatide positivity, although heterogeneous by a clinical and neurophysiological point of view, had the most severe neuropathic manifestations and a higher disability score at nadir (P < 0.001). These patients had a better response to both intravenous immunoglobulin therapy and rituximab.

Conclusions:   Our results suggest that antiganglioside/sulfatide-positive patients form a relevant portion of patients with MGUS-associated polyneuropathy seen in tertiary care centers and should be considered in future studies on treatment response.