Frequency and relevance of IgM intrathecal synthesis in multiple sclerosis

Abstract

Using a new ELISA method we have measured the IgM concentration in the serum and the cerebrospinal fluid CSF from 110 neurological patients. Among there, 41 had multiple sclerosis (MS), 48 other inflammatory diseases (OID), including 30 AIDS, and 21 non-inflammatory neurological diseases (NID). A highly significant correlation was established between results with native IgM and the dithiothreitol reduced IgM. An intrathecal synthesis (ITS) of IgM was detected using the CSF IgM/CSF albumin ratio, the IgM index and a quantitative formula in 33 patients: nine MS, 23 OID (including 18 AIDS) and one NID. The frequency of IgM ITS was 22% in MS patients, 48% in the OID (60% in AIDS) and 5% in the NID groups. This ITS was not impaired by an increase in serum IgM concentration or by a blood-CSF barrier damage. These facts confirm that intrathecal immunity is not a "steady-state" related to the general immunity but a specific response restricted to the central nervous system. Conversely, CSF IgM increase and IgM ITS were closely related (p < 10(-6) ). In addition, IgM ITS and IgG ITS were found to be highly correlated in OID, especially in AIDS patients: such correlation was not observed in the MS group. No significant correlations were observed between IgM ITS and any of the clinical parameters in MS patients. These results suggest the probable specificity of IgM ITS in MS patients.

Oligoclonal IgM bands in the cerebrospinal fluid of patients with relapsing MS to inform long-term MS disability

“…The present study highlights the relationship between the presence of OCMB and long-term unfavorable In PwMS, intrathecal production of IgM ranges from 14% to 68.75%, 3,8,10,11,13,22,31,32 while the presence of OCMB and LS-OCMB has been described in nearly half 4,5,21 or a third 5,19,20,33 of PwMS which was consistent with our data. Intrathecal IgM synthesis has been consistently associated with a higher risk of clinically isolated syndrome (CIS) progression to RMS, 10,34 the appearance of relapses, 3 and MRI lesion load.…”

“…36 The aforementioned review also noted the need for further studies of long-term prognosis 35 and indeed, associations of intrathecal IgM synthesis with disability have been found in some studies, 9,32 but not in others. 3,31 Again, controversial results have been communicated for OCMB and/or LS-OCMB. Specifically, both these markers of IgM synthesis have been associated with a faster rate of reaching an EDSS ⩾ 3.0 21 and ⩾4.0.…”

CSF profile in primary progressive multiple sclerosis: Re-exploring the basics

“…Data reports on the prevalence of intrathecal IgM synthesis in PPMS are scarce. We only found one such study, which reported elevated IgM index in 32.3% of its 29 patients with chronic progressive MS[ 47 ]. Increased IgM-index values might include false-positive results due to the linear formula used.…”