IgA Subclasses and Free Light Chains in Celiac Disease: A Pilot Study

Celiac disease (CD) is an autoimmune enteropathy of the small intestine affecting genetically susceptible individuals, characterized by an aberrant immune response to gliadin and sustained IgA-driven inflammation. IgA exists in two main subclasses, IgA1 and IgA2, which differ in distribution and function, but their profile in CD remains poorly characterized. Circulating free light chains (FLCs) are markers of B-cell activation and immune dysregulation, yet their role in CD has not been fully explored. The aim of this study was to characterize IgA subclasses and FLC profiles in newly diagnosed celiac patients. We analyzed sera from 108 CD patients and 29 healthy controls, assessing conventional serological markers (anti-tissue transglutaminase and anti-endomysial antibodies), together with total IgA, IgA1, IgA2, and FLC levels using a turbidimetric method. CD patients exhibited higher total IgA levels and an increased IgA1/IgA2 ratio, alongside a decreased k/λ ratio; these differences remained significant after adjustment for age and sex. When combined in a multivariable logistic model, these biomarkers yielded an AUC of 0.827, suggesting that the parameters identified in the univariate analyses provide complementary, non-redundant information that jointly highlights a reorganization of the humoral immune response. Due to the limited sample size, our results need confirmation in larger cohorts. However, our findings suggest a reorganization of the IgA compartment in CD, with selective expansion of IgA1 and preferential λ light chain usage, highlighting coordinated alterations in the humoral immune response. The integration of such markers, potentially in combination with -omics approaches, may contribute to a more refined and less invasive characterization of celiac disease.