Clinical and serological features of systemic autoimmune overlap in AQP4-IgG positive neuromyelitis optica spectrum disorder: a Mexican cohort study.
TL;DR
Systemic autoimmune overlap was present in approximately one in five patients and the overlap group showed more frequent systemic autoantibody positivity and a predominance of optic neuritis at onset, but disability measures, treatment patterns, and most clinical outcomes were similar between groups.
Abstract
Background
Neuromyelitis optica spectrum disorder (NMOSD) often coexists with systemic autoimmune disease, but the clinical meaning of this overlap remains incompletely defined, particularly in Latin American populations.
Objective
To describe the prevalence, autoimmune spectrum, and clinical and serological features of systemic autoimmune overlap in a Mexican cohort of aquaporin 4 immunoglobulin G (AQP4-IgG)-positive NMOSD.
Methods
We conducted a retrospective single center cohort study of patients who fulfilled the 2015 international diagnostic criteria for NMOSD and were followed between 2002 and 2023. The analytic cohort was restricted to AQP4-IgG-positive patients. Demographic, clinical, treatment, and systemic autoantibody data were collected from medical records. Analyses were primarily descriptive and comparative. Time to second relapse was assessed as an exploratory secondary outcome.
Results
Among 86 AQP4-IgG-positive patients, 16 (18.6%) had a coexisting systemic autoimmune disease. Sjögren syndrome (37.5%) and systemic lupus erythematosus (12.5%) were the most frequent diagnoses. Patients with autoimmune overlap showed a broader burden of systemic autoantibody positivity, with antinuclear antibodies, anti-SSA, anti-SSB, and anti-dsDNA being the most commonly detected markers. Optic neuritis was the most common presenting event in the overlap group (68.8%), though disability measures at baseline and follow-up were otherwise similar between groups. Treatment regimens did not differ significantly between patients with and without systemic autoimmune disease. In exploratory analysis, an association between anti-SSB positivity and a shorter time to second relapse was observed (hazard ratio 2.30, 95% CI 1.05-5.10 in univariable analysis; hazard ratio 2.34, 95% CI 1.05-5.21 in multivariable analysis). However, this hypothesis-generating finding was based on a limited number of events and wide confidence intervals and should be interpreted with caution.
Conclusion
In this Mexican cohort of AQP4-IgG-positive NMOSD, systemic autoimmune overlap was present in approximately one in five patients. The overlap group showed more frequent systemic autoantibody positivity and a predominance of optic neuritis at onset, but disability measures, treatment patterns, and most clinical outcomes were similar between groups. The relapse-related findings, including the observed association with anti-SSB positivity, should be considered exploratory and interpreted strictly as hypothesis-generating. Confirmation in larger prospective multicenter studies with standardized antibody testing is required before any prognostic implications can be inferred.