Anti-sulfatide/galactocerebroside antibodies in immunoglobulin M paraproteinemic neuropathies.

BACKGROUND AND PURPOSE: Anti-sulfatide antibodies have been observed in heterogeneous neuropathies and their clinical relevance is still controversial. Whether the combination of sulfatide with galactocerebroside would increase sensitivity or specificity of enzyme-linked immunosorbent assay testing compared to sulfatide alone was assessed. METHODS: Immunoglobulin M (IgM) antibodies to sulfatides, galactocerebroside and combined sulfatide and galactocerebroside (Sulf/GalC) were measured in 229 neuropathy patients, including 73 with IgM paraproteinemic neuropathy [62 with anti-myelin-associated glycoprotein (anti-MAG) antibody] and 156 with other neuropathies. Results from 27 patients with IgM monoclonal gammopathy without neuropathy and 28 healthy subjects served as control. RESULTS: Thirty-three patients showed increased titers of anti-sulfatide antibodies, 28 of whom had an IgM paraproteinemic neuropathy (P < 0.0001). When evaluating the reactivity for the combination Sulf/GalC, 57/229 patients were found to be positive, including 36/73 (49%) with IgM paraproteinemic neuropathy (P < 0.0001). Patients with known anti-sulfatide antibodies also showed anti-Sulf/GalC reactivity, with increased titers in 48.5% of the cases. Testing for anti-Sulf/GalC antibodies allowed 24 additional patients to be detected (eight with IgM paraproteinemic neuropathies), who had no reactivity to the individual glycolipids. Amongst the 11 subjects with IgM paraproteinemic neuropathy who were negative for anti-MAG antibodies, only two were reactive to sulfatide, whilst six (55%) were found to be positive when tested against the combination of sulfatide and galactocerebroside. CONCLUSIONS: Testing for both sulfatide and galactocerebroside in IgM paraproteinemic neuropathies seems to increase the sensitivity compared to anti-sulfatide antibodies alone (49% and 39%, respectively, with a slightly reduced specificity, from 97% to 87%), helping the characterization of otherwise undefined neuropathy that could benefit from immunomodulatory therapy.

Anti-sulfatide IgM antibodies in peripheral neuropathy: to test or not to test?

BACKGROUND AND PURPOSE: Anti-sulfatide immunoglobulin M (IgM) antibodies have been associated with different forms of neuropathies but their diagnostic role in neuropathy remains unclear. METHODS: The clinical association of increased titers of anti-sulfatide IgM antibodies in 570 patients with neuropathy and related disorders examined in our laboratory since 2004 was reviewed. Sera were tested by enzyme-linked immunosorbent assay at the initial serum dilution of 1:32,000 and titrated by serial two-fold dilution. In all positive patients IgM antibodies to myelin-associated glycoprotein (MAG) were also measured by western blot. RESULTS: High titers of anti-sulfatide antibodies were found in 39 patients including 33 (85%) who also had anti-MAG IgM. Six patients did not have anti-MAG IgM including five in whom moderately increased anti-sulfatide titers were associated with different forms of neuropathy. One patient with a demyelinating neuropathy and IgM monoclonal gammopathy had markedly increased anti-sulfatide titers (1:256,000). CONCLUSIONS: Increased titers of anti-sulfatide IgM antibodies are not infrequent in patients with neuropathy where they are often associated with a concomitant reactivity to MAG. A selective reactivity to sulfatide, however, is rarely found and is associated with different forms of neuropathy limiting its usefulness in the diagnosis of neuropathy.