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Intrathecal IgM Synthesis Is Associated with Spinal Cord Manifestation and Neuronal Injury in Early MS
Author(s) -
Oechtering Johanna,
Lincke Therese,
Schaedelin Sabine,
Décard Bernhard F.,
Maceski Aleksandra,
Orleth Annette,
Meier Stephanie,
Willemse Eline,
Buchmann Arabella,
Khalil Michael,
Derfuss Tobias,
Benkert Pascal,
Heijnen Ingmar,
Regeniter Axel,
Müller Stefanie,
Achtnichts Lutz,
Lalive Patrice,
Salmen Anke,
Pot Caroline,
Gobbi Claudio,
Kappos Ludwig,
Granziera Cristina,
Leppert David,
Schlaeger Regina,
Lieb Johanna M.,
Kuhle Jens
Publication year - 2022
Publication title -
annals of neurology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.764
H-Index - 296
eISSN - 1531-8249
pISSN - 0364-5134
DOI - 10.1002/ana.26348
Subject(s) - intrathecal , spinal cord , spinal cord injury , medicine , neuroscience , anesthesia , biology
Objective Intrathecal Immunoglobulin M synthesis (IgM Intrathecal Fraction (IF) + ) and spinal MRI lesions are both strong independent predictors of higher disease activity and severity in multiple sclerosis (MS). We investigated whether IgM IF + is associated with spinal cord manifestation and higher neuroaxonal damage in early MS. Methods In 122 patients with a first demyelinating event associations between (1) spinal versus (vs) non‐spinal clinical syndrome (2) spinal vs cerebral T2‐weighted (T2w) and (3) contrast‐enhancing (CE) lesion counts with IgG IF + (vs IgG IF − ) or IgM IF + (vs IgM IF − ) were investigated by logistic regression adjusted for age and sex, respectively. For serum neurofilament light chain (sNfL) analysis patients were categorized for presence or absence of oligoclonal IgG bands (OCGB), IgG IF and IgM IF (>0% vs 0%, respectively): (1) OCGB − /IgG IF − /IgM IF − ; (2) OCGB + /IgG IF − /IgM IF − ; (3) OCGB + /IgG IF + /IgM IF − ; and (4) OCGB + /IgG IF + /IgM IF + . Associations between categories 2 to 4 vs category 1 with sNfL concentrations were analyzed by robust linear regression, adjusted for sex and MRI parameters. Results Patients with a spinal syndrome had a 8.36‐fold higher odds of IgM IF + (95%CI 3.03–23.03; p < 0.01). Each spinal T2w lesion (odds Ratio 1.39; 1.02–1.90; p = 0.037) and CE lesion (OR 2.73; 1.22–6.09; p = 0.014) was associated with an increased risk of IgM IF + (but not of IgG IF + ); this was not the case for cerebral lesions. OCGB + /IgG IF + /IgM IF + category patients showed highest sNfL levels (estimate:1.80; 0.55–3.06; p < 0.01). Interpretation Intrathecal IgM synthesis is strongly associated with spinal manifestation and independently more pronounced neuroaxonal injury in early MS, suggesting a distinct clinical phenotype and pathophysiology. ANN NEUROL 2022;91:814–820