Increased Epstein-Barr virus reactivation cycles linked to development of rheumatoid arthritis

By Samr Mahmoud, MS
Published February 17, 2022

Key Takeaways

  • This study found that subjects with elevated Epstein–Barr virus (EBV) antibodies will eventually develop rheumatoid arthritis (RA), suggesting that EBV reactivation cycles increase during the preclinical period of RA. 

  • A combination of EBV reactivation and rheumatoid factor may contribute to the development of RA.

RA is a systemic autoimmune disease of unknown etiology. Environmental and genetic factors are thought to contribute to the pathogenesis of RA.

Why This Study Matters 

EBV has been long suspected to play a role in the pathogenesis of RA. Previous studies have shown that RA patients have altered immune responses to EBV. However, the role of EBV during the preclinical disease period has not been adequately explored. To address this need, this study sought to determine if EBV infection drives the development of RA or if it is a consequence of RA-related autoimmunity.

Study Design

This study included 83 subjects with RA and 83 age-, gender-, and race-matched control participants without RA. Investigators collected sera from participants during the pre-RA and post-RA diagnosis periods.

The collected serum samples were tested for the presence of the following anti-EBV antibodies: anti-EBV nuclear antigen 1 IgG isotype; anti-viral capsid antigen (anti-VCA) isotypes IgG and IgA; and anti-early antigen (EA) isotypes IgG and IgA. Investigators also tested sera for RA-related autoantibodies and IgG–cytomegalovirus (CMV) antibodies. 

Results and Conclusions

Investigators found that IgG-EA antibody levels were elevated in RA subjects (0.82 ± 0.72) compared to control subjects (0.49 ± 0.28).

In participants with RA, increased IgG-EA levels in the preclinical period were significantly associated with increased serum IgM-RF levels (P=0.007). However, this correlation was not found in control subjects without RA (P=0.15). Investigators did not find a difference in IgG-CMV antibody levels between the two groups.

Related Research

Consider these findings from similar research studies:

  • Serum levels of antibodies against EBV encoded EBNA1 protein differ in patients with RA and in their unaffected twins in comparison to healthy subjects (Source). 

  • There is a strong association between EBV presence and development of lymphoproliferative disorders in RA patients (Source).

Original Source 

Fechtner S, Berens H, Bemis E, et al. Antibody responses to epstein–barr virus in the preclinical period of rheumatoid arthritis suggest the presence of increased viral reactivation cycles. Arthritis & Rheumatology. Published online February 13, 2022:art.41994.

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