Usefulness of chemokine C-C receptor 7- /programmed cell death-1+ follicular helper T cell subset frequencies in the diagnosis of autoimmune hepatitis

Hepatol Res. 2019 Sep;49(9):1026-1033. doi: 10.1111/hepr.13356. Epub 2019 Jun 3.

Abstract

Aim: A significant concern for autoimmune hepatitis (AIH) patients is diagnostic specificity. Delayed treatment due to delayed diagnosis leads to poor survival. We recently reported that chemokine C-C receptor 7 (CCR7)- /programmed cell death-1 (PD-1)+ follicular helper T (Tfh) cells could be involved in AIH pathogenesis. We hypothesized that Tfh cell frequencies might contribute to AIH diagnosis.

Methods: Peripheral blood was collected from 12 patients with AIH from April 2013 to March 2016, as well as 24 patients with hepatitis B virus (HBV) infection and 44 healthy controls (HC). Mononuclear cells were separated using a Ficoll gradient, and surface markers were investigated using flow cytometry.

Results: The frequency of CCR7- PD-1+ Tfh cells was significantly higher in AIH patients (39.1 ± 8.6) compared to that in HC (25.1 ± 7.9%, P < 0.01) and HBV patients (22.7 ± 7.8, P < 0.01). The area under the receiver operating characteristic curve for the frequency of the CCR7- PD-1+ Tfh cell subset for AIH and HC and AIH and HBV was 0.905 and 0.927, respectively. The frequency of the CCR7- PD-1+ Tfh cell subset was not correlated with International Autoimmune Hepatitis Group (IAIHG) scoring, Simplified AIH scoring, or Japanese diagnostic guidelines (R = 0.10, 0.947; R = 0.0008, 0.180; and R = 0.348, 0.558, respectively). Therefore, these frequencies could diagnose AIH patients who were not diagnosed with the IAIHG or simplified AIH scores.

Conclusions: The frequency of the peripheral CCR7- PD-1+ Tfh cell subset could be useful for diagnosing AIH even in patients who were not diagnosed with IAIHG or simplified AIH scores.

Keywords: autoimmune hepatitis; diagnosis; follicular helper T cell.