Can Multiple Sclerosis (MS) cause a positive Antinuclear Antibody (ANA) test?

Multiple Sclerosis Can Cause a Positive ANA Test

Multiple sclerosis (MS) can cause a positive antinuclear antibody (ANA) test in approximately 27-43% of patients, though this positivity is not associated with systemic lupus erythematosus or other connective tissue diseases. 1, 2

Prevalence of ANA Positivity in MS

• ANA positivity has been documented in 42.7% of MS patients in recent studies, with titers ≥1/320 in nearly half of these positive cases 1
• Earlier research found ANA in 26.7% of relapsing-remitting MS patients and 30.4% of chronic progressive MS patients 2
• Up to 60% of MS patients may have antinuclear autoantibodies according to some studies 3

Clinical Significance and Associations

• ANA positivity in MS patients does not correlate with extra-neurological manifestations typical of connective tissue diseases 1
• ANA positivity in MS is significantly associated with:
  • Presence of IgG oligoclonal bands (47.1% in OCB-positive vs 16.6% in OCB-negative patients) 1
  • Active disease status (52.6% in patients with relapse vs 25.9% in patients in remission) 1
• Primary and secondary progressive MS have shown higher autoantibody frequency than relapsing-remitting or benign MS 4

Differential Diagnosis Considerations

• ANA positivity can complicate the differential diagnosis between MS and rheumatic diseases with central nervous system involvement (RDwCNS) 3
• When distinguishing between ANA-positive MS and RDwCNS, additional testing is recommended:
  • MRZ-reaction (MRZR) - antibody indices against neurotropic viruses (positive in 80.9% of MS patients vs 20% in RDwCNS) 3
  • Oligoclonal bands (positive in 94.3% of MS patients vs 28.6% in RDwCNS) 3
  • Testing for specific extractable nuclear antigens (ENA) antibodies (more common in RDwCNS) 3

Temporal Pattern of Autoantibodies in MS

• Up to 86% of MS patients may be autoantibody-positive during acute disease stages 4
• Only 30% remain positive during remission phases 4
• This fluctuation suggests that autoantibody production in MS reflects ongoing immune dysregulation rather than a primary pathogenic mechanism 1, 4

Clinical Implications

• The presence of ANA in MS patients does not alter the clinical presentation, disease course, or prognosis 5
• MS patients with autoimmune features, including those with positive ANA titers, should not be excluded from clinical trials as their disease characteristics are not significantly different from other MS patients 5
• ANA positivity in MS is considered a false-positive finding that likely reflects systemic immune dysregulation rather than having pathogenic relevance to MS itself 2

Practical Approach to ANA Testing in MS

• ANA testing should be interpreted with caution in MS patients due to the high frequency of positivity 1, 2
• When ANA is positive in suspected MS, additional testing for specific autoantibodies (anti-dsDNA, ENA) is recommended to rule out concurrent autoimmune diseases 3
• A positive ANA at titers ≥1:80 has relatively low specificity (74.7%) for systemic autoimmune diseases 6
• Using a higher cut-off of 1:160 improves specificity to 86.2% while maintaining appropriate sensitivity (95.8%) 6