Patients with autoimmune diseases have an altered activity of the PD-1 pathway and proportions of Epstein-Barr virus infected cells in benign lymphadenopathies

Christer Sundström,Peter Hollander

doi:10.1016/j.imbio.2021.152069

Abstract

Patients with autoimmune diseases (AD) have an increased risk to develop benign lymphadenopathies compared to patients without AD. The aim with this study was to determine the role of the PD-1 pathway and the number of cells harboring Epstein-Barr virus (EBV) in benign lymphadenopathies in patients with AD (cases) compared to patients without AD (controls). Pathology registries were screened to identify patients with biopsies diagnosed as benign lymphadenopathy and medical journals were reviewed for information on AD. Immunohistochemical stainings (PD-1 and PD-L1) and EBER in situ hybridization for EBV were applied on lymph node biopsies in patients with AD (n = 22) and patients without AD (n = 57). The case group was compared with the control group with Wilcoxon-signed rank, chi-square and Fischeŕs exact test. There was a statistically significantly higher proportion of PD-1+ cells and a tendency for a lower prevalence of PD-L1+ and EBV+ cells in cases compared to controls. Apparently, patients with AD have an altered immune response as revealed in benign lymphadenopathies compared to patients without AD. If this association might be a piece of the puzzle for the increased risk of development of lymphomas in patients with AD remains to be determined.

Highlights

More than 90% of people worldwide are infected with Epstein-Barr virus (EBV) (Rickinson, 2014)
autoimmune diseases (AD) included as cases were rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), Sjogrens syndrome, sarcoidosis, Mb Bechterew, Mb Still, psoriatic arthritis, polymyalgia rheumatica (PMR), autoimmune hepatitis and primary biliary cirrhosis (Table 1)
Histopathological reclassification of cases and controls were per formed by the authors (Swerdlow and Bosman, 2016) and divided into categories based on the predominant histolopathological patterns: follicular hyperplasia; interfollicular hyperplasia; sinus histiocytosis; necrosis; granulomatous inflammation; sclerosis (Weiss and O’Malley, 2013) and Piringer lymphadenitis (Lin and Kuo, 2001)

Summary

Introduction

More than 90% of people worldwide are infected with Epstein-Barr virus (EBV) (Rickinson, 2014). Following primary infection, where a minority of infected individuals develops infectious mononucleosis (IM), the virus enters a latent state in B cells. EBV-infected B cells may be reactivated and proliferate, in immunocom promised patients (Rickinson, 2014). EBV has an oncogenic potential and is etiologically linked to several different B and T cell lymphomas (Thorley-Lawson et al, 2013; Hue et al, 2020). Immunocompromised patients more often develop EBV+ lymphomas than immunocompetent individuals (Thorley-Lawson et al, 2013). Patients with an impaired immune system are unable to keep the latently EBV-infected B cells under control, which permits EBV+ B cells to proliferate and possibly undergo genetic changes (Rickinson, 2014)

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