Shared pathogenic mechanisms between systemic lupus erythematosus and autoimmune hepatitis: A unified view of...

Systemic lupus erythematosus (SLE) and autoimmune hepatitis (AIH) are clinically distinct autoimmune disorders characterized by multisystem involvement and liver-restricted inflammation, respectively; nevertheless, they exhibit considerable overlap in their underlying immunopathogenic features.

To provide a systematic synthesis of recent advances in genetics, immunology, and microbiome science, and to delineate the convergent pathogenic mechanisms that underpin both SLE and AIH.

A comprehensive literature review was conducted using PubMed and other databases up to 2025, focusing on shared genetic, cellular, and microbial determinants in SLE and AIH. Core topics included genetic susceptibility loci, breakdown of immune tolerance, T-cell dysregulation, innate immune activation, and alterations in gut microbiota composition and function.

SLE and AIH share several genetic risk variants, including HLA-DRB1*03:01, PTPN22, STAT4, and TNFAIP3. Both diseases are characterized by defective central and peripheral immune tolerance, imbalances in Th17/Treg and Tfh/Tfr compartments, and aberrant B-cell activation. Innate immune pathways-encompassing Toll-like receptor and NLRP3 inflammasome signaling as well as complement dysregulation-further amplify inflammation. Moreover, gut dysbiosis and perturbations in microbial metabolites, such as short-chain fatty acids, bile acids, and tryptophan derivatives, function as key mediators linking intestinal homeostasis to both systemic and hepatic autoimmunity.

SLE and AIH represent overlapping entities along a unified autoimmune spectrum, driven by shared genetic susceptibility, convergent immune dysregulation, and microbial influences. This review advances an integrated immunological framework that bridges systemic and organ-specific autoimmunity, underscores the pivotal role of innate immunity and gut-liver crosstalk, and provides a mechanistic rationale for cross-disease therapeutic strategies targeting these common pathways.