The AC-18 cytoplasmic pattern as a non-specific serological correlate of central nervous system disorders: A...

The AC-18 cytoplasmic discrete dots pattern, associated with anti-GW body autoantibodies, is traditionally linked to systemic autoimmunity, but its relationship with CNS involvement remains under-explored. We aimed to characterize the AC-18 pattern as a non-specific serological correlate of central nervous system (CNS) involvement in a case-control cohort.

Out of 52,196 ANA tests screened, the AC-18 pattern was identified in 397 tests, corresponding to a test-level frequency of 0.76%. After applying exclusion criteria and removing duplicate records, 300 unique patients with isolated AC-18 positivity were included in the final cohort. This group was compared with 300 seronegative controls. Multivariate models evaluated whether AC-18 was independently associated with CNS disorders (including primary headaches, cerebrovascular events, demyelinating and neurodegenerative conditions), adjusting for age, sex, and autoimmunity.

Overall neurological disorders were significantly more frequent in AC-18-positive patients than controls (17.7% vs. 6.7%, p < 0.001). CNS disorders were also more frequent in AC-18-positive patients (12.7% vs. 4.0%, p < 0.001). Following adjustment for age, sex, and autoimmunity, AC-18 positivity remained associated with CNS disorders (adjusted OR 3.50, 95% CI 1.78-6.87, p < 0.001). ROC analysis of the multivariable models showed moderate discriminatory performance for overall neurological disorders (AUC 0.72) and CNS-related outcomes (AUC 0.71).

AC-18 positivity was associated with CNS involvement in this retrospective case-control cohort. Given the heterogeneous nature of CNS diagnoses and the moderate discriminatory performance of the multivariable models, AC-18 should be interpreted as an exploratory, non-specific serological correlate rather than a diagnostic or pathogenic biomarker.