Cerebrospinal Fluid IgM Index Correlates with Cranial MRI Lesion Load in Patients with Multiple Sclerosis

Abstract

In multiple sclerosis intrathecal IgM synthesis correlates with an unfavourable disease course. Whether this reflects a pathogenic role of IgM, possibly in conjunction with complement, is a matter of debate. In a cross-sectional study we measured intrathecal synthesis of IgM and the complement component C3, and on cranial MRI lesion load and central brain atrophy in clinically active patients, 17 relapsing-remitting, 16 secondary progressive. Correlative analysis showed that in relapsing-remitting patients CSF IgM index correlated with cranial MRI T₂ and T₁ lesion load, and central brain atrophy; and the C3 index correlated with T₂ lesion load. In secondary progressive patients CSF IgM index correlated with periventricular T₂ lesion load. Our data are in favour of a pathogenic role of IgM in multiple sclerosis.

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

“…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. [7][8][9][10][11][12] In line with these results and with a recent review showing a clear association between intrathecal IgM synthesis and markers of inflammatory activity in MS, 35 we found that OCMB were associated with a fivefold increase in the odds of using high-efficacy DMDs as a proxy of inflammatory activity during the course of MS. An increase in the IgM index was not associated with either ARR or with the use of high-efficacy DMDs. One potential explanation could be that freezing can induce IgM aggregation, which might affect the quantitative analyses.…”

“…With all the above considered, it has become crucial to develop and validate early MS features that inform long-term outcomes in order to guide the decisionmaking process in PwMS. In this sense, a consistent association has been proposed between clinical and radiological inflammatory activity and relevant cerebrospinal fluid (CSF) markers, like intrathecal IgM synthesis [3][4][5][6][7][8][9][10][11][12][13] or CSF neurofilament light chain protein (NfL) levels. [14][15][16][17][18] However, the relationship between such markers and central nervous system (CNS) neuroaxonal injury 6,19 or disability 17,18,[20][21][22][23] has yet to be fully substantiated.…”

Intrathecal synthesis of IgM measured after a first demyelinating event suggestive of multiple sclerosis is associated with subsequent MRI brain lesion accrual

“…Only one study has assessed the potential relationship between intrathecal IgM synthesis and conventional MRI findings in patients with MS. 17 This cross-sectional study demonstrated a significant association between IgM index and T2 lesion load in patients with MS. 17 These results may reflect a pathogenic role of IgM in plaque formation. However, the cross-sectional design of this study prevents any inference concerning the potential causal relationship between IgM synthesis and lesion formation.…”

Prognostic role of intrathecal IgM synthesis in multiple sclerosis: Results from a clinical series

“…Taking into account that our MRI findings are based on a limited sample size, we found that ITMS+ patients had a higher T1 lesion load at brain MRI performed within 1 year from the first DE. Previous studies found that ITMS was associated with a higher baseline T1-lesion load 26,27 and brain atrophy, 27,28 suggesting that IgM could be involved in tissue damage and axonal loss.…”