Neuropathy Associated With Anti‐Chondroitin Sulfate C IgM Antibodies

Abstract

Chondroitin Sulfate C (ChS‐C), is a glycosaminoglycan present in the membranes of neurons and axons. Anti‐ChS‐C IgM antibodies have been reported in patients with predominantly sensory neuropathy (PN) often associated with IgM monoclonal gammopathy, but also in some neurological controls. In order to evaluate the frequency and clinical correlate of anti‐ChS‐C IgM antibodies, we tested them by a new Covalink ELISA technique in sera from 206 patients with IgM monoclonal gammopathy including 79 with PN (PN+IgM) with unknown IgM reactivity, 65 with PN with antibodies to the myelin‐associated glycoprotein and 62 without PN, and from 33 patients with PN of other causes, 30 with other neurological and non‐neurological diseases and 23 normal subjects. We only found high titers of anti‐ChS‐C IgM in two patients (1/128,000 and 1/256,000 respectively) with IgM monoclonal gammopathy: one had Waldenström Macroglobulinemia diagnosed seven years before and a 3 year history of slowly progressive limb weakness, finger paresthesias, unsteady gait and occasional nocturnal cramps. Neurological examination revealed a predominantly large‐fiber sensory neuropathy with mild distal atrophy and weakness in upper and lower limbs. Electrophysiological and morphological studies were suggestive of a predominantly demyelinating neuropathy. The other patient had IgM MGUS without PN at the time of antibody testing but developed finger paresthesias seven years later, when he had decreased position sense and abnormal sensory nerve conduction studies. In conclusion high titers of anti‐ChS‐C IgM, though infrequent, were always associated with the presence or development of sensory PN in patients with IgM M‐protein, supporting a possible role for these antibodies in the neuropathy.