Fumarate hydratase-specific T cell response in Chinese patients with autoimmune hepatitis - 03/04/18

Doi : 10.1016/j.clinre.2017.12.003

Yan Zhao ^a,^{^{1
These authors contributed equally to this work.}}, Yanli Li ^b,^{^{1
These authors contributed equally to this work.}}, Dantong Zhao ^a, Haiping Zhang ^a, Yanmin Liu ^c, Huiyu Liao ^c, Yonghong Zhang ^d,^⁎ , Huiping Yan ^a,^⁎
^a Center for clinical laboratory, Beijing You’An Hospital, Capital Medical University, 100069 Beijing, China
^b Beijing University of Chinese Medicine Third Affiliated Hospital, Beijing, China
^c Study Centre of Autoimmune liver disease, Beijing You’An Hospital, Capital Medical University, 100069 Beijing, China
^d Interventional therapy center, Beijing You’An Hospital, Capital Medical University, 100069 Beijing, China

^⁎Corresponding author.^⁎⁎Co-corresponding author at: Study Centre of Autoimmune liver disease, Beijing You’An Hospital, Capital Medical University, Beijing 100069, China.

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Highlights

•	FH can induce T cells to release cytokines and chemokines, and to produce autoantibodies.
•	The FH-specific T cell response was associated with the target organ inflammation levels.
•	FH may be an antigen in AIH patients and be involved in the pathogenesis of AIH.

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Summary

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.

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Keywords : Autoimmune hepatitis, Fumarate hydratase, T cell response, Cytokines