The Immunological Landscape of Biliary Atresia: Focus on Th2 and Th17 Profiles 2330296

Abstract

Abstract Introduction Our understanding of the underlying causes and immunological mechanisms of biliary atresia remains limited. Hence, the study aimed to investigate the Th2 and Th17 immune profiles and autoimmune features in infants with biliary atresia. Methods A comprehensive analysis of immune markers, T and B cell subsets, cytokines, gene expressions, autoantibodies, and serum immunoglobulin levels was conducted in a prospective case-control study, correlating the results with liver histology and immunohistochemistry. Results A heightened surface expression of costimulatory molecules (CD40/CD40L and ICOS), increased plasma B cell percentages, and raised IgA and IgG levels were observed. Plasma cytokines, i.e., IL-2, IL-4, IL-6, IL-10, IL-17, TNF, and IFNγ, were significantly elevated with four-fold higher expression of RORγt compared to FOXP3 in all patients. Liver histology displayed characteristic features of BA with dense lymphoplasmacytic infiltrate comprising CD3+ T and CD20+ B cells around portal tracts and weak positivity for autoantigens and autoantibodies. Conclusion The presence of Th1/Th2 imbalance and Th17 immune response, characterised by an imbalance in proinflammatory gene expression, heightened secretion of cytokines, overactivation, and expansion of lymphocytes, along with the detection of autoantibodies, collectively point to immune-mediated mechanisms playing a notable role in the progression of biliary atresia. Funding Source ICMR, India Topic Categories Immune Mechanisms of Human Disease (HUM)