This paper says that IgM is a risk factor, but in fact there is people that never gets igM. It could be that IgM is a different kind of MS with a more severe prognosis.
Intrathecal IgM production is a strong risk factor for early conversion to multiple sclerosis
To evaluate intrathecal immunoglobulin M (IgM) production, as compared to previously established risk factors, as risk factor for conversion from clinically isolated syndrome (CIS) to multiple sclerosis (MS) and to explore the association of intrathecal IgM production with onset age and radiologic and CSF findings in CIS/early MS.
Comprehensive CSF data, including oligoclonal immunoglobulin G (IgG) bands (OCB) and calculated intrathecal IgM and IgG production, were collected in a prospective study of 150 patients with CIS/early MS with regular clinical and MRI assessments.
Intrathecal IgM production >0% occurred in 23.2% (33/142) of patients, who were on average 5 years younger at disease onset (p = 0.013) and more frequently had infratentorial lesions (18/32, 56.3%) than patients without intrathecal IgM production (33/104, 31.7%, p = 0.021). In multivariable Cox regression analyses, intrathecal IgM production in patients with a CIS (n = 93, median clinical and MRI follow-up 24 and 21 months) was strongly associated with conversion to MS according to the McDonald 2010 criteria (hazard ratio [95% confidence interval] 3.05 [1.45–6.44], p = 0.003) after adjustment for age (0.96 [0.93–1.00], p = 0.059), OCB (0.92 [0.33–2.61], p = 0.879), intrathecal IgG production (0.98 [0.48–1.99], p = 0.947), and radiologic evidence of dissemination in space (2.63 [1.11–6.22], p = 0.028).
Intrathecal IgM production is a strong independent risk factor for early conversion to MS and may thus represent a clinically meaningful marker for predicting future disease activity in patients with a CIS.
Immunoglobulin M oligoclonal bands: Biomarker of targetable inflammation in primary progressive multiple sclerosis
To identify a biomarker distinguishing patients who, despite a primary progressive multiple sclerosis (PPMS) clinical course, may nonetheless benefit from immune therapy.
The presence or absence of both immunoglobulin (Ig) G and IgM oligoclonal bands (OCB) was blindly examined in paired cerebrospinal fluid (CSF) and serum samples from a large PPMS patient cohort, and related to clinical and imaging evidence of focal inflammatory disease activity.
Using both cross‐sectional samples and serial sampling in a subgroup of patients followed prospectively as part of the placebo‐controlled OLYMPUS study of rituximab in PPMS, we found that the presence of CSF‐restricted IgM OCB (but not of IgG OCB) is associated with an active inflammatory disease phenotype in PPMS patients. This finding was confirmed in an independent, multicenter validation cohort.
The presence of CSF IgM OCB may be a biomarker for a subset of PPMS patients with more active inflammatory disease, who may benefit from immune‐directed treatments.
Intrathecal IgM synthesis demonstrated either as cerebrospinal fluid (CSF)-restricted oligoclonal (o-) IgM bands or calculated using various formulas has been linked to more aggressive multiple sclerosis (MS) course. However, the proportion of MS patients showing intrathecal IgM synthesis varies largely between studies. We aimed to explore the relation between different formulas and results of o-IgM, and to assess the frequency of o-IgM bands in an unselected series of samples.
432 samples were analyzed for o-IgM, o-IgG and quantitative measures of IgM and IgG synthesis. IgM index and formulas of Reiber, Auer and Öhman were compared to the result of the o-IgM test.
At the cut-off commonly used, the non-linear formulas for intrathecal synthesis were specific (>94%) but rather insensitive (<40% even at a cut-off of 4 CSF-restricted bands) compared to o-IgM. No significant difference was noted in the performance of different formulas. At a cut-off of 4 bands, 61 % of MS patients, but none of the controls were positive for o-IgM.
Formulas for intrathecal IgM synthesis are insensitive compared to o-IgM. We propose to evaluate samples with 2 or 3 extra-CSF IgM bands as borderline and only samples with 4 or more as definitely positive.
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