Yonsei Med J.  2020 Jan;61(1):100-102. 10.3349/ymj.2020.61.1.100.

Autoimmune Hepatic Failure Following Acute Hepatitis A is Accompanied by Inflammatory Conversion of Regulatory T Cells

Affiliations
  • 1Laboratory of Immunology and Infectious Diseases, Graduate School of Medical Science and Engineering, Korea Advanced Institute of Science and Technology (KAIST), Daejeon, Korea. ecshin@kaist.ac.kr
  • 2Department of Internal Medicine, Yonsei University College of Medicine, Yonsei Liver Center, Severance Hospital, Seoul, Korea. drpjy@yuhs.ac

Abstract

To evaluate the pathophysiology of autoimmune hepatitis (AIH) following acute hepatitis A (AHA) in immunologic aspects, we performed multi-color flow cytometry with peripheral blood mononuclear cells of a patient who underwent liver transplantation due to AIH-induced liver failure. Unlike general AHA patients, the proportion of tumor necrosis factor-α-producing Treg cells remained high for 6 months after diagnosis of AHA until she underwent a liver transplantation. The conversion of Treg cells into mediators of inflammation may have played a role in the autoimmune pathogenesis following AHA.

Keyword

Autoimmune hepatitis; acute hepatitis A; regulatory T cells; inflammatory conversion of Treg cells

MeSH Terms

Diagnosis
Flow Cytometry
Hepatitis A*
Hepatitis*
Hepatitis, Autoimmune
Humans
Inflammation Mediators
Liver Failure*
Liver Transplantation
Necrosis
T-Lymphocytes, Regulatory*
Inflammation Mediators

Figure

  • Fig. 1 (A) The results of subsequent liver function tests. The total bilirubin (blue line), aspartate aminotransferase (AST) (red line), and alanine aminotransferase (ALT) (yellow line) levels showed repeated deterioration during the course of the disease. Clinical courses, including admission, discharge, and liver transplantation, are marked by black arrows. Three months after initial hospitalization, the patient was revealed to be positive for anti-nuclear antibody (ANA) (>1:640) and perinuclear anti-neutrophil cytoplasmic antibodies (p-ANCA). Her immunoglobulin M (IgM) anti-hepatitis A virus (anti-HAV) antibody status remained positive until after liver transplantation. (B-D) Flow cytometric analyses of Treg cells producing tumor necrosis factor-α (TNF-α), interferon-γ (IFN-γ), and interleukin-17A (IL-17A). Treg cells expressed higher levels of TNF-α (B), IFN-γ (C), and IL-17A (D) compared to Treg cells from a healthy donor. Healthy donor data are representative of those from six healthy donors. (E) TNF-α, IFN-γ, and IL-17A production by Treg cells of the patient gradually decreased to normal levels over the 6 months following liver transplantation (black arrow represents the time-point of liver transplantation).


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