HIGH-LEVELS OF CEREBROSPINAL-FLUID IGM BINDING TO MYELIN BASIC-PROTEIN ARE ASSOCIATED WITH EARLY BENIGN COURSE IN MULTIPLE-SCLEROSIS

We assessed human myelin basic protein (MBP) binding IgM levels in the CSF. MBP is the most studied putative antigen in multiple sclerosis ( MS) and immune responses directed against it may be involved in the de myelination process. We also correlated these levels with EDSS score a nd other parameters of disease progression and prognosis, both at the time of CSF analysis and during follow-up. CSF IgM anti-MBP levels wer e assayed by measuring total IgM levels with solid-phase ELISA in CSF samples from 66 patients with relapsing-remitting MS, 11 subjects with out neurological diseases, 20 patients with non-inflammatory neurologi cal diseases and 7 patients with lymphocytic meningitis, before and af ter immunoabsorption with human MBP. Confirmation of IgM binding speci ficity was performed by immunoblotting of positive CSF samples onto MB P coated-nitrocellulose sheets. Clinical evaluation (disability score, number and time of attacks) was performed during a mean follow-up of 2.7 +/- 1.1 years. 23 of 66 relapsing-remitting MS patients (33.8%) ha d elevated IgM anti-MBP levels. In this patient subgroup, IgM anti-MBP levels correlated with the IgM index (r = 0.71; P = 0.0001), but not with CSF/serum albumin (r = 0.08; P = 0.72). In the first year of foll ow-up, patients with low IgM anti-MBP suffered from more numerous atta cks than those with elevated levels (0.86 +/- 0.63 versus 0.43 +/- 0.5 8; P = 0.017). Patients with high IgM binding to MBP had a first attac k during follow-up in a significantly higher time than those with low binding (28.87 +/- 4.7 versus 17 +/- 2.6 months, respectively; P = 0.0 05) and reached a decrease of 0.5 EDSS point significantly faster than those with low IgM (16.17 +/- 1.2 versus 29.7 +/- 2.6 months, respect ively; P = 0.0002). A similar significant finding was observed when th e time to reach low disability score (EDSS less than or equal to 2.0) was analyzed (10.7 +/- 2 versus 25.7 +/- 3.3 months, respectively; P = 0.014). These findings demonstrate that in a subgroup of MS patients, elevated CSF levels of IgM anti-MBP are associated with early favorab le course and therefore suggest that IgM binding to MBP could be a pos sible prognostic marker in relapsing-remitting MS to select early MS p atients for future trials.