Stool Mucosal Immune Protein–Cytokine Interconnections in Children with Autism Spectrum Disorder: An Age-Adjusted Partial Correlation Analysis

Children with autism spectrum disorder (ASD) exhibit gut mucosal immune alterations, but the co-regulatory architecture linking stool immune proteins and cytokines within the same cohort remains unstudied. In 115 children (74 ASD, 41 controls; age 5–18 years), seven stool immune proteins (IgA subclasses, α1-antitrypsin and calprotectin subunits) were quantified by UHPLC-MS/MS and ten by Luminex—chemokines eotaxin/CCL11 and IL-8/CXCL8 plus eight cytokines—each normalised to total protein. Age-adjusted partial Spearman correlations were computed for all 70 protein–cytokine pairs per stratum, using Benjamini–Hochberg correction, bootstrap confidence intervals and Fisher r-to-z tests. No pair survived FDR correction in any stratum. IgA1 and IL-1β/TP correlated positively across all strata (full cohort ρ = 0.409, 95% CI 0.131–0.634, n = 62; controls 0.583; ASD 0.210), with no significant between-group difference (Fisher z = 1.70, p = 0.090). Multiple imputation attenuated this to ρ = 0.265 (95% CI 0.055–0.452). An inverse trend between IL-1β/TP and CARS score (ρ = −0.336, n = 41) did not survive correction (p-FDR = 0.576). This power-limited, hypothesis-generating study identifies an exploratory IgA1–IL-1β mucosal axis present across groups, with no confirmed between-group difference. Adequately powered multi-centre studies are required.