Antinuclear antibodies in early multiple sclerosis reflect systemic lupus erythematosus shared risk factors

After a clinically isolated syndrome (CIS), antinuclear antibodies (ANAs) are often measured in diagnostic workup of inflammatory diseases. Although ANAs are associated with systemic lupus erythematosus (SLE), increased prevalence has been observed in multiple sclerosis (MS) with controversial significance. We determined in a prospective cohort study the association of ANAs measured during diagnostic workup with shared MS and SLE risk factors, clinical characteristics and disease course in CIS patients aged 18-65 years. ANA positivity was found in 60/364 (16.5%) participants and associated with female sex (83.3% vs. 67.4%, p = 0.01) and higher anti-EBNA1 IgG titres (median 1450.0 vs. 588.0 U/ml, p < 0.01), compared to ANA-negative participants. ANA-positive participants were more often homozygous carriers of HLA-DRB1*15:01 (12.8% vs. 2.7%, p < 0.01), but did not show higher MS or SLE genetic risk. Clinical characteristics and early disease course, estimated with Cox regression, were similar between participants with or without ANAs, regardless of a subsequent MS diagnosis. This study helps clinicians better interpret ANA positivity in patients with CIS. Our data demonstrate that ANA positivity during diagnostic workup for MS does not indicate a different disease course, but may reflect shared genetic and environmental risk factors for MS and SLE. Further studies should explore shared disease mechanisms.