Diagnostic role of anti-neural antibodies in dysimmune neuropathies

Antibodies against several neural antigens have been associated with neuropathies (PN), including anti-myelin-associated glycoprotein (MAG) IgM in predominantly sensory demyelinating PN associated with IgM monoclonal gammopathy (PN+IgM), anti-sulfatide IgM in predominantly sensory axonal PN or demyelinating PN+IgM, anti-GM1 or -GD1a IgM in motor neuropathies with (MMN) or without conduction block (MN), anti-GM1 or GD1a IgG in Guillain-Barré syndrome (GBS), anti-GM2 IgM in MMN, MN and GBS, anti-GQ1b IgM in sensory PN+IgM, anti-GQ1b IgG in Fisher syndrome (FS) or ophthalmoplegic GBS, and anti-Hu IgG in paraneoplastic subacute sensory neuropathy (SSN). There is, however, an open debate not only on the pathogenetic relevance of these antibodies but also on their possible diagnostic usefulness. To determine the diagnostic role of these antibodies we reviewed the diagnosis of positive patients among the over 2500 patients tested in our laboratory from 1985 through 1998. Among the 710 patients tested for anti-MAG IgM by immunoblot, all those with titers >1/100,000 and 95% of those with titers >1/6400 but only 25% of those with titers <1/3200 had PN+IgM. A similarly strict correlation between antibody titers and clinical presentation was observed among 564 patients tested by ELISA for anti-sulfatide IgM, 530 for anti-GDI a IgG and IgM, and 224 for anti-GM2 IgM; all patients with anti-sulfatide IgM >1/8000 had chronic inflammatory demyelinating polyneuropathy (CIDP) or demyelinating PN+IgM; all those with anti-GD1a >1/5120 had demyelinating PN+IgM (IgM antibodies) or GBS (IgG); and all those with anti-GM2 IgM >1/640 had GBS, MMN or MN. Lower titers were not associated with specific clinical forms. Of the over 1500 sera tested by ELISA for anti-GM1 antibodies, 88% of those with anti-GM1 IgG >1/640 had GBS, while only 62% of those with anti-GM1 IgM >1/320 had a dysimmune neuropathy, including GBS, CIDP, PN+IgM and MN. The sensitivity and specificity for a positive anti-GM1 IgM test was identical using a recently proposed Covalink ELISA technique. Among the 308 patients tested for anti-GQ1b antibodies by ELISA, only titers >1/100 were always associated with FS or ophthalmoplegic GBS in the case of IgG and with PN+IgM in that of IgM. Of the 333 tested for anti-Hu IgG by immunoblot only those with titers >1/6400 always had SSN/limbic encephalitis associated with lung carcinoma. These data show that the diagnostic value of anti-neural antibodies strictly depends on their titers and that while antiMAG, -sulfatide, -GD1a and -GQ1b IgM, and anti-GM1, -GD1a, -GQ1b and -Hu IgG are highly predictive for specific neuropathies, anti-GM1 and anti-GM2 IgM are more generically predictive for a dysimmune PN rather than for MMN or MN.