Fumarate hydratase-specific T cell response in Chinese patients with autoimmune hepatitis.

PURPOSE: Fumarate hydratase (FH) is expressed in the serum of patients with autoimmune hepatitis (AIH). The specific involvement of FH-specific T cell response is currently unknown. The aim of the study was to assess the frequency and clinical significance of FH-specific T cell response in AIH.

METHODS: This was a prospective study of 42 consecutive patients admitted to the clinical study center of autoimmune liver disease of our Hospital, Capital Medical University (China) between January 2011 and December 2014. PBMCs were collected and the FH-specific T cell response was detected by Elispot. Cytokines and antibody responses were assessed.

RESULTS: Among the 42 AIH patients, 57.1% showed a positive response to FH peptides. The difference in FH-specific T cell response frequency among AIH patients and control groups was significant (P<0.001). The FH peptides induced the secretion of CD4+ and CD8+ T cells. The FH-specific T cell response in patients with active disease was stronger than in those with remission (P=0.0283). FH-specific T cell response in patients with active disease showed a positive association with ALT (r=0.4712, P=0.0098) and AST (r=0.3924, P=0.0352) levels. The magnitude of the FH-specific T cell response correlated with the HAI score (r=0.7290, P=0.0047) and anti-FH titer (r=0.6457, P=0.0093).

CONCLUSION: FH-specific T cell response may be detected in the blood of patients with AIH and seems to be associated with AIH disease progression. FH-specific T cell response could be a pathogenic cause of AIH.