Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Meta-Analysis
. 2022 Jan 10;14(1):115.
doi: 10.3390/v14010115.

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  1 , Danijela Miljanovic  1 , Ivana Lazarevic  1 , Ivica Jeremic  2 , Aleksa Despotovic  3 , Milka Grk  4 , Andja Cirkovic  5
Affiliations
Meta-Analysis

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 et al. Viruses. .

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.

Keywords: EBV; lymphoma; lymphoproliferative disorders; meta-analysis; rheumatoid arthritis.

PubMed Disclaimer

Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Flow diagram.
Figure 2
Figure 2
Meta-analysis of the prevalence of positive EBV result in RA-LPD patients (red dot represents the point estimate—prevalence and black frame represents 95%CI of the point estimate for the data from each of included studies).
Figure 3
Figure 3
Meta-analysis of the difference in the positive EBV result in RA-LPD patients and all controls (blue dot represent the odds ratio and black frame 95% CI of the odds ratio from each of the included studies. black arrows show that upper and/or lower limit of the 95%CI of odds ratio is below or above defined values on the x axis).
Figure 4
Figure 4
Meta-analysis of the difference in the positive EBV result in RA-LPD and LPD patients (blue dot represent the odds ratio and black frame 95% CI of the odds ratio from each of the included studies. black arrows show that upper and/or lower limit of the 95%CI of odds ratio is below or above defined values on the x axis).
Figure 5
Figure 5
Meta-analysis of the difference in the positive EBV result in RA-LPD patients and patients with autoimmune diseases other than RA and LPD (blue dot represent the odds ratio and black frame 95% CI of the odds ratio from each of the included studies. black arrows show that upper and/or lower limit of the 95%CI of odds ratio is below or above defined values on the x axis).
Figure 6
Figure 6
Meta-analysis of the prevalence of the positive EBV result in RA-LPD patients by the continent of origin (red dot represents the point estimate—prevalence and black frame represents 95%CI of the point estimate for the data from each of included studies).
Figure 7
Figure 7
Meta-analysis of the difference in the positive EBV result in RA-LPD patients and all controls by the continent of origin (blue dot represent the odds ratio and black frame 95% CI of the odds ratio from each of the included studies. black arrows show that upper and/or lower limit of the 95%CI of odds ratio is below or above defined values on the x axis).
See this image and copyright information in PMC

References

    1. Trier N.H., Holm B.E., Heiden J., Slot O., Locht H., Lindegaard H., Svendsen A., Nielsen C.T., Jacobsen S., Theander E., et al. Antibodies to a strain-specific citrullinated Epstein-Barr virus peptide diagnoses rheumatoid arthritis. Sci. Rep. 2018;8:3684. doi: 10.1038/s41598-018-22058-6. - DOI - PMC - PubMed
    1. Tokuhira M., Saito S., Suzuki K., Higashi M., Momose S., Shimizu T., Mori T., Kimura Y., Amano K., Okamoto S., et al. Clinicopathological features of clinical methotrexate-related lymphoproliferative disorders. Leuk. Lymphoma. 2019;60:2508–2515. doi: 10.1080/10428194.2019.1585841. - DOI - PubMed
    1. Simon T.A., Thompson A., Gandhi K.K., Hochberg M.C., Suissa S. Incidence of malignancy in adult patients with rheumatoid arthritis: A meta-analysis. Arthritis Res. Ther. 2015;17:212. doi: 10.1186/s13075-015-0728-9. - DOI - PMC - PubMed
    1. Mercer L.K., Davies R., Galloway J.B., Low A., Lunt M., Dixon W.G., Watson K.D., Symmons D.P.M., Hyrich K.L. Risk of cancer in patients receiving non-biologic disease-modifying therapy for rheumatoid arthritis compared with the UK general population. Rheumatology. 2013;52:91–98. doi: 10.1093/rheumatology/kes350. - DOI - PMC - PubMed
    1. Takada H., Kaneko Y., Nakano K., Tanaka M., Fujii T., Saito K., Sugimoto N., Sasaki S., Saito S., Saito R., et al. Clinicopathological characteristics of lymphoproliferative disorders in 232 patients with rheumatoid arthritis in Japan: A retrospective, multicenter, descriptive study. Mod. Rheumatol. 2021:1–9. doi: 10.1080/14397595.2021.1899570. - DOI - PubMed

Publication types