Patients with multiple sclerosis (MS) displayed high levels of IgM, IgA and IgG in the cerebrospinal fluid (CSF). In particular, intrathecal immunoglobulin M (IgM) synthesis has been suggested as a prognostic marker of a more rapid and severe disease progression in MS.
Investigate whether IgM production is associated with a specific CSF inflammatory profile in naïve MS patients at the time of diagnosis.
CSF protein levels of IgM, IgA, IgG and of 34 inflammatory mediators were analysed using Bio-Plex Multiplex immunoassay in 103 naïve relapsing-remitting MS patients (RRMS) and 36 patients with other neurological disorders.CSF IgM levels were also correlated with clinical and neuroradiological measures (advanced 3T-MRI parameters) at diagnosis and after 2 years of follow-up.
A 45.6% increase in CSF IgM levels was found in MS patients compared to controls (p=0.013), while no significant differences in IgG (p=0.360) and IgA (p=0.700) levels between the two groups have been detected. CSF IgM levels correlated with higher paired CSF levels of CXCL13 (p=0.039), CCL21 (p=0.023), IL-10 (p=0.025), IL-12p70 (p=0.020), CX3CL1 (p=0.036) and CHI3L1 (p=0.048) and were associated with earlier age of patients at diagnosis (p=0.008), white matter lesions (WMLs) number (p=0.039) and disease activity (p=0.033) after 2 years of follow-up.
IgM are the most abundant immunoglobulins present at diagnosis in naïve RRMS patients compared to other neurological conditions at the time of diagnosis and their association with further molecules related to both B-cell immunity (IL-10) and recruitment (CXCL13 and CCL21) and to macrophage/microglia activity (IL-12p70, CX3CL1 and CHI3L1) suggestsa link between humoral and innate intrathecal immunity.