New Evidence of Significant Association between EBV Presence and Lymphoproliferative Disorders Susceptibility in Patients with Rheumatoid Arthritis: A Systematic Review with Meta-Analysis.

Ana Banko,Ivana Lazarevic,Danijela Miljanovic,Andja Cirkovic,Aleksa Despotovic,Ivica Jeremic,Milka Grk

doi:10.3390/v14010115

Ana Banko, Ivana Lazarevic + Show 5 more

Open Access

https://doi.org/10.3390/v14010115

Copy DOI

Journal: Viruses	Publication Date: Jan 10, 2022
Citations: 9	License type: CC BY 4.0

Affiliation: University of Belgrade

Abstract

Development of lymphoproliferative disorders (LPDs) is one of the well-known life-threatening complications in rheumatoid arthritis (RA) patients. However, there is a lack of definitive conclusions regarding the role of Epstein-Barr virus (EBV) activity in RA initiation and progression, especially in promoting LPDs. A systematic review and meta-analysis of studies that reported an EBV positive result in RA-LPD patients and controls were conducted. Studies published before 27 July 2021 were identified through PubMed, Web of Science, and SCOPUS. A total of 79 articles were included in the systematic review. The prevalence of EBV positive result among RA-LPD patients was 54% (OR = 1.54, 95% CI = 1.45–1.64). There was a statistically significant association between EBV presence and LPD susceptibility in RA patients in comparison with all controls (OR = 1.88, 95% CI = 1.29–2.73) and in comparison with LPD patients only (OR = 1.92, 95% CI = 1.15–3.19). This association was not shown in comparison with patients with autoimmune diseases other than RA who developed LPD (OR = 0.79, 95% CI = 0.30–2.09). This meta-analysis confirmed a high prevalence of EBV in the RA-LPD population. Furthermore, it provides evidence for the association between EBV presence and LPD susceptibility in RA patients, but not in those with other autoimmune diseases who developed LPD.

Highlights

Rheumatoid arthritis (RA) is a polygenic, multifactorial, and chronic inflammatory systemic autoimmune disease that affects up to 1% of the world’s population [1]
Removed, the title and abstracts were evaluated for 804 articles
This study provided the first systematic review with a meta-analysis that confirmed a

Summary

Introduction

Rheumatoid arthritis (RA) is a polygenic, multifactorial, and chronic inflammatory systemic autoimmune disease that affects up to 1% of the world’s population [1]. One of the well-known life threatening complications in RA patients is the development of lymphoproliferative disorders (LPDs), including malignant lymphoma. The evolution of LPDs in RA patients is complex and still enigmatic. Multiple risk factors have been identified, including RA-induced inflammation, infections, the use of immunosuppressive drugs for RA treatment, such as methotrexate (MTX), and a number of genetic factors [2]. The increased risk of developing malignant lymphoma in RA patients compared with the general population has been well documented [3]. The risk of Hodgkin lymphoma (HL)development, one of the most frequently identified LPDs, might be as much as 12 times higher in RA patients [4]. An earlier diagnosis of LPDs in RA patients favors better disease outcomes, their clinical and histopathological diversity represent a significant diagnostic challenge [5]

Methods

Results

Discussion

Conclusion