Key result
Low baseline MxA mRNA linked to higher long-term risk of ≥9 new T2-lesions in early MS.
Why the study?
Homeostatic MxA mRNA levels are potentially correlated with inflammatory disease activity in MS and could play an important role in MS pathology, but long-term associations were not established.
Are baseline blood MxA mRNA levels associated with long-term disease activity and progression in early multiple sclerosis?
Cohort (n=116)
No
Are baseline blood MxA mRNA levels associated with long-term disease activity and progression in early multiple sclerosis?
Odds Ratio: 0.16 (95% CI 0.04–0.66)
p-value: p=0.012
Baseline blood MxA mRNA levels are associated with long-term development of T2-lesions on MRI and relapses in early MS, highlighting the role of the endogenous interferon-beta system.
Low baseline MxA mRNA was associated with more long-term T2 lesions and relapses; supports endogenous IFN-β relevance but leaves biomarker utility open pending validation.
Background: Myxovirus resistance protein A (MxA) is a protein that is upregulated by interferon-beta. Homeostatic MxA mRNA levels are potentially correlated with inflammatory disease activity in multiple sclerosis (MS) and could have an important role in MS pathology. Aim: To investigate the association between myxovirus resistance protein A (MxA) mRNA levels in blood and disease activity and progression in MS over a long-term follow-up period. Methods: Baseline blood MxA mRNA levels were determined in a prospective cohort of 116 untreated patients with a clinically isolated syndrome (CIS) or early relapsing remitting MS (RRMS), and related to long-term relapses, radiological disease activity, clinical scores [Expanded Disability Status Scale (EDSS), timed-25-foot walk (T25FW), 9-hole-peg test (9HPT)], MS type, and disease modifying therapy (DMT) use. Results: Low MxA mRNA levels were associated with the occurrence of ≥9 T2-lesions on MRI imaging and the occurrence of relapses during long-term follow-up (median 11 years, IQR 5.91-13.69 years). MxA mRNA levels were not associated with EDSS, T25FW, 9HPT, and MS subtype. Conclusion: Baseline MxA mRNA levels are associated with long-term development of T2-lesions on MRI-scans in our cohort. This confirms the relevance of the endogenous interferon-beta system in the occurrence of MS disease activity.
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Coerver et al. (2022) conducted a cohort in Clinically isolated syndrome (CIS) or early relapsing remitting MS (RRMS) (n=116). Low baseline MxA mRNA levels (<0.075) vs. High baseline MxA mRNA levels (≥0.075) was evaluated on Cumulative number of ≥9 new T2-lesions on MRI during follow-up (OR 0.16, 95% CI 0.04-0.66, p=0.012). Low baseline MxA mRNA levels in patients with early multiple sclerosis were significantly associated with the development of 9 or more new T2-lesions on MRI over a median 11-year follow-up.
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