Polyneuropathy syndromes associated with serum antibodies to sulfatide and myelin‐associated glycoprotein

Abstract

We studied a series of 64 patients with sensory +/- motor peripheral neuropathies by comparing clinical and physiologic features to serum antibody reactivity against compounds containing sulfated carbohydrate moieties. We determined antibody reactivity by an enzyme-linked immunosorbent assay (ELISA) using purified glycolipids and glycoproteins as antigens, and we used high-performance thin-layer chromatography and Western blotting to test the specificity of results. Twelve patients with high titers of IgM antibodies directed against the myelin-associated glycoprotein (MAG) had sensory-motor polyneuropathies with physiologic evidence of demyelination. IgM antibody reactivity to MAG was associated with an IgM serum M protein in five patients. Eight other patients, most with sensory greater than motor polyneuropathies, had high titers of antibody reactivity to sulfatide but not of IgM to MAG. Two had an associated IgM paraprotein. None of the patients with selective serum antisulfatide activity had predominantly demyelinating features on physiologic testing. We conclude that (1) high ELISA titers of antibodies to MAG may be more common than previously suspected in patients with chronic demyelinating sensory-motor neuropathies, and (2) the presence of high titers of antisulfatide antibodies in serum may provide clues to the pathogenesis of otherwise idiopathic, axonal, predominantly sensory neuropathies.

Autoantibodies to cerebroside sulphate (sulphatide) in leprosy

“…These antibodies may have a role in disease, as some patients with neuropathy associated with antibodies to myelin-associated glycoprotein showed improvement after immunosuppressive treatment [26]. Anti-sulphatide antibodies, associated with sensory gangliopathy [6], and now leprosy, may have a similar ability to cause or exacerbate sensory neuron and axonal degeneration. The involvement of the dominant autoreactive group of antibodies that express the 16/6 idiotype, of which leprosy-derived TH3 is a member [27], in anti-sulphatidemediated damage, seems highly feasible.…”

“…Amongst this group of antibodies, some bind to sulphatide (cerebroside sulphate; 3-sulphated galactosylceramide), and these are predominant in axonal sensory neuropathy [6]. A sulphated pentasaccharide antigen that reacts with monoclonal IgM from patients with this demyelinating neuropathy as well as the mouse MoAb HNK-1, which reacts with a receptor on human natural killer (NK) cells, has been isolated from human peripheral nerves [7].…”

Treatment of Autoimmune Neuromuscular Diseases with High-Dose Intravenous Immune Globulin

“…The most likely processes are humoral, such as antibodies against myelin, which can lead to complement activation (4 1,43). Autoantibodies to various myelin antigens have been identified in patients with GBS, CIDP, and paraproteinemic neuropathies (41, 47,49). Although the exact pathogenic role of these antibodies is not clear, some of the antibodies in GBS fix complement and their titer does correlate with disease activity (41).…”

“…One can envision that such protective antibodies may be naturally prevalent in subclinical cases of GBS. Other anti-peripheral nerve antibodies have also been detected in patients with inflammatory neuropathies and include anti-GMl, anti-myelin-associated glycoprotein, and antiglucolipids (49). Healthy adults also have low titers of such anti-peripheral nerve antibodies, which may be the stimulus for the cross-reactive antiidiotypes responsible for the efficacy of IVIG (49,72).…”

“…Other anti-peripheral nerve antibodies have also been detected in patients with inflammatory neuropathies and include anti-GMl, anti-myelin-associated glycoprotein, and antiglucolipids (49). Healthy adults also have low titers of such anti-peripheral nerve antibodies, which may be the stimulus for the cross-reactive antiidiotypes responsible for the efficacy of IVIG (49,72). Another explanation is the solubilization of immune complexes by the IVIG or the competition with complement-binding, anti-peripheral nerve antibodies.…”