Tumor necrosis factor receptor superfamily member 13B mutation-associated chronic cholangitis with cirrhosis: A case report and review of literature

Abstract

BACKGROUND

The transmembrane activator and calcium-modulator and cyclophilin ligand interactor, encoded by tumor necrosis factor receptor superfamily member 13B (TNFRSF13B), maintains immune homeostasis through bidirectional regulation of B-cell function. This study presents a case of a 56-year-old female with chronic cholangitis and cirrhosis associated with a heterozygous missense mutation in TNFRSF13B.

CASE SUMMARY

A 56-year-old female with thalassemia trait and recurrent ascending cholangitis following cholangiojejunostomy presented with cirrhosis of unclear etiology. Despite serial hospitalizations for cholestatic decompensation and comprehensive evaluations-including serological profiling with elevated antinuclear antibody titers and histopathological assessment-no conventional cirrhosis triggers were identified. The patient presented with elevated serum immunoglobulin A (IgA) and IgG, and no apparent immune dysfunction. Two magnetic resonance imaging examinations revealed absence of the left hepatic lobe and gallbladder, no dilation of intrahepatic bile ducts, and inflammatory lesions in the hepatic hilum, cirrhosis, and splenomegaly. Pathological review of the resected left hepatic lobe demonstrated extensive plasma cell infiltration (MUM1+/IgG+) with focal iron deposits. Whole-exome sequencing uncovered a heterozygous missense variant (c.436G>C, p.Ala146Pro) in TNFRSF13B. She was diagnosed with TNFRSF13B mutation-associated chronic cholangitis and cirrhosis. Treatment with antibiotics, hepatoprotective drugs, and ursodeoxycholic acid led to symptom resolution, and she was discharged with ongoing therapy.

CONCLUSION

TNFRSF13B mutation may impair B-cell negative regulation, promoting cholangitis, and cirrhosis. Iron overload and bacterial infection accelerate disease progression.

Keywords: Autoimmune liver disease; Chronic cholangitis; TNFRSF13B gene; B cell homeostasis; Case report

Core Tip: Tumor necrosis factor receptor superfamily member 13B (TNFRSF13B) maintains immune homeostasis through bidirectional regulation of B cell function. This case report presents a case where a TNFRSF13B mutation that may impair TACI’s negative regulatory control over B cell activity, causing B cell hyperactivation, sustained local inflammatory responses, and chronic cholangitis progressing to cirrhosis. This finding provides a novel immunogenetic perspective for understanding certain autoimmune liver diseases of unknown etiology.