Prevalence of autoimmune comorbidities in aquaporin 4-immunoglobulin G positive neuromyelitis optica spectrum disorder: a systematic review and meta-analysis.

Background

Autoimmune comorbidities in aquaporin-4-immunoglobulin G (AQP4-IgG)-positive neuromyelitis optica spectrum disorder (NMOSD) may be associated with increased disease severity and therapeutic challenges, yet prevalence estimates vary considerably. Some variability may reflect differences in population characteristics, geography, health systems, and methodology.

Objectives

To estimate the prevalence of autoimmune comorbidities in AQP4-IgG-positive NMOSD.

Methods

We searched MEDLINE, Embase, Cochrane CENTRAL, Global Health, and Global Index Medicus for studies published from inception up to November 13, 2025. Four reviewers independently screened and extracted data in duplicate. Eligible studies were published since 2005 and reported autoimmune comorbidity prevalence among people with AQP4-IgG-positive NMOSD. Pooled proportions with 95% confidence intervals (CIs) were estimated using generalized linear mixed models with random effects. Subgroup analyses examined variation by continent and gross national income classification. We assessed study quality using the Joanna Briggs Institute Critical Appraisal Tool. We assessed publication bias by visually inspecting a funnel plot.

Results

Seventy studies encompassing 7843 participants were included. The pooled prevalence of at least one autoimmune comorbidity was 22.2% (95% CI, 19.3-25.3, I2 = 78%). Sjögren's syndrome was most frequent (4.6%), followed by systemic lupus erythematosus (SLE) (3.0%) and autoimmune thyroid disease (2.6%). Prevalence varied by region (Europe, 31.1%; North America, 23.9%; South America, 21.9%; Asia, 16.8%) and by income group (high-income, 25.1%; lower-middle-income, 7.0%).

Conclusion

Autoimmune comorbidities were frequently documented in AQP4-IgG-positive NMOSD. Estimates should be interpreted cautiously because ascertainment methods were heterogeneous and validated diagnostic criteria were infrequently reported. Regional differences may reflect population, ascertainment, and healthcare-system factors.