A broad range of antiphospholipid IgM are elevated across different multiple sclerosis clinical phenotypes

Area of Science:

• Neuroimmunology
• Autoimmunity
• Biomarker Discovery

Background:

• Demyelination in multiple sclerosis (MS) triggers immune responses and autoantibodies.
• Elevated antiphospholipid antibodies (aPL) are observed in MS, but their specific reactivities across MS subtypes are not well-characterized.
• Antiphospholipid antibodies (aPL) are antibodies against phospholipids and associated proteins, implicated in antiphospholipid syndrome (APS).

Purpose of the Study:

• To explore and compare IgM reactivities to various phospholipids and APS criteria aPL across different stages of multiple sclerosis (MS): clinically isolated syndrome (CIS), relapsing-remitting MS (RRMS), secondary progressive MS (SPMS), and primary progressive MS (PPMS).
• To assess the potential of these aPL as biomarkers for MS diagnosis and progression.
• To investigate associations between aPL levels and demographic factors, disease duration, disability (EDSS), and disease-modifying therapy (DMT) use.

Main Methods:

• Cross-sectional study evaluating serum samples from 35 healthy controls (HC), 20 CIS, and 83 MS participants (33 RRMS, 30 SPMS, 20 PPMS).
• Enzyme-linked immunosorbent assay (ELISA) was used to measure IgM levels to phosphatidyl-choline (PC), -ethanolamine (PE), -inositol (PI), -serine (PS), -sphingomyelin (SM), cardiolipin (CL), and β2-glycoprotein I (βGP).
• Statistical analyses were performed to compare aPL levels between groups and assess associations with clinical and demographic variables, controlling for confounders.

Main Results:

• Elevated aPL levels to all tested phospholipids were associated with a higher likelihood of being CIS compared to HC.
• Elevated aPL to PI, PS, SM, CL, and βGP were associated with SPMS compared to RRMS, independent of age, sex, disease duration, EDSS, and DMT use.
• Positivity to individual phospholipids and broad positivity (≥3 aPL) were more common in CIS and SPMS.
• Older age in CIS, longer disease duration in SPMS, and higher EDSS in PPMS were associated with increased aPL.
• DMT use tended to correlate with lower aPL titers, significantly for aPL to PE.

Conclusions:

• Antiphospholipid antibody reactivities exhibit distinct patterns across different multiple sclerosis (MS) subtypes.
• Specific aPL profiles may serve as potential biomarkers for distinguishing MS phenotypes, particularly CIS and SPMS.
• Further longitudinal studies are warranted to elucidate the role of aPL in MS pathophysiology and their response to treatment.