Intrathecal IgM production is a strong risk factor for early conversion to multiple sclerosis

Item Type:	Article
Title:	Intrathecal IgM production is a strong risk factor for early conversion to multiple sclerosis
Creators Name:	Pfuhl, C. and Grittner, U. and Gieß, R.M. and Scheel, M. and Behrens, J.R. and Rasche, L. and Pache, F.C. and Wenzel, R. and Brandt, A.U. and Bellmann-Strobl, J. and Paul, F. and Ruprecht, K. and Oechtering, J.
Abstract:	OBJECTIVES: 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. METHODS: 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. RESULTS: 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). CONCLUSION: 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.
Keywords:	Age of Onset, Demyelinating Diseases, Disease Progression, Immunoglobulin G, Immunoglobulin M, Multiple Sclerosis, Oligoclonal Bands, Risk Factors, Severity of Illness Index
Source:	Neurology
ISSN:	0028-3878
Publisher:	American Academy of Neurology
Volume:	93
Number:	15
Page Range:	e1439-e1451
Date:	8 October 2019
Official Publication:	https://doi.org/10.1212/WNL.0000000000008237
PubMed:	View item in PubMed

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