Gender-related disparities in the frequencies of PD-1 and PD-L1 positive peripheral blood T and B lymphocytes in patients with alcohol-related liver disease: a single center pilot study

Beata Kasztelan-Szczerbinska; Katarzyna Adamczyk; Agata Surdacka; Jacek Rolinski; Agata Michalak; Agnieszka Bojarska-Junak; Mariusz Szczerbinski; Halina Cichoz-Lach

doi:10.7717/peerj.10518

Gender-related disparities in the frequencies of PD-1 and PD-L1 positive peripheral blood T and B lymphocytes in patients with alcohol-related liver disease: a single center pilot study

PeerJ. 2021 Jan 20:9:e10518. doi: 10.7717/peerj.10518. eCollection 2021.

Authors

Beata Kasztelan-Szczerbinska¹, Katarzyna Adamczyk¹, Agata Surdacka², Jacek Rolinski², Agata Michalak¹, Agnieszka Bojarska-Junak², Mariusz Szczerbinski³, Halina Cichoz-Lach¹

Affiliations

¹ Department of Gastroenterology with Endoscopy Unit, Medical University of Lublin, Poland, Lublin, Poland.
² Department of Clinical Immunology, Medical University of Lublin, Poland, Lublin, Poland.
³ Department of Gastroenterology with Endoscopy Unit, Public, Academic Hospital No 4, Lublin, Poland.

Abstract

Background: Exposure to excessive alcohol consumption dysregulates immune signaling. The programed cell death 1 (PD-1) receptor and its ligand PD-L1 play a critical role in the protection against immune-mediated tissue damage. The aim of our study was evaluation of the PD-1/PDL-1 expression on peripheral T and B lymphocytes, its correlation with markers of inflammation and the severity of liver dysfunction in the course of alcohol-related liver disease (ALD).

Material and methods: Fifty-six inpatients with ALD (38 males, 18 females, aged 49.23 ± 10.66) were prospectively enrolled and assigned to subgroups based on their: (1) gender, (2) severity of liver dysfunction (Child-Pugh, MELD scores, mDF), (3) presence of ALD complications, and followed for 30 days. Twenty-five age- and gender-matched healthy volunteers served as the control group. Flow cytometric analysis of the PD-1/PD-L1 expression on peripheral lymphocyte subsets were performed.

Results: General frequencies of PD-1/PD-L1 positive T and B subsets did not differ between the ALD and control group. When patients were analyzed based on their gender, significantly higher frequencies of PD1/PD-L1 positive B cells in ALD females compared to controls were observed. ALD females presented with significantly higher frequencies of PD-1+ and PD-L1+ B cells, as well as PD-L1+ all T cell subsets in comparison with ALD males. The same gender pattern of the PD-1/PDL1 expression was found in the subgroups with mDF > 32 and MELD > 20. No correlations of PD-1+ and PD-L1+ lymphocyte percentages with mDF, CTP and MELD scores, nor with complications of ALD were observed. Significant correlations of PD-L1 positive B cell frequencies with conventional markers of inflammation were found.

Conclusions: Gender-related differences in the frequencies of PD-1/PD-L1 positive T and B cells were observed in patients with ALD. Upregulation of PD-1+/PD-L1+ lymphocytes paralleled both the severity of alcoholic hepatitis and liver dysfunction in ALD females.

Keywords: Alcohol-related liver disease; B lymphocytes; Programmed cell death receptor ligand 1; Programmed cell death-1 receptor; T lymphocytes.

Grants and funding

This study was supported by the Research Grants from the Medical University of Lublin, Poland (PW369; 2015-2017). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.