Serum Epstein-Barr virus DNA, detected by droplet digital PCR, correlates with disease activity in patients with rheumatoid arthritis

Clin Exp Rheumatol. 2018 Sep-Oct;36(5):778-784. Epub 2018 Mar 20.

Abstract

Objectives: To study the prevalence of asymptomatic activation of Epstein-Barr virus (EBV) in patients with rheumatoid arthritis (RA) and to analyse the correlation of serum EBV DNA with the disease activity.

Methods: The level of EBV DNA was determined by droplet digital PCR assay from the serum of 46 DMARD naive early RA (ERA) and 22 chronic RA (CRA)-patients at study onset. Follow-up samples from 31 ERA and 16 CRA patients were obtained after starting or modifying the anti-rheumatic treatment. EBV DNA was also measured from 33 healthy controls and 9 patients with adult onset Still's disease (AOSD). Disease activity was assessed by the disease activity score (DAS28).

Results: At baseline, EBV DNA was detected in the serum of 7 of the 46 ERA patients all of whom had moderate or high disease activity. In the follow-up samples, 11 of 31 patients were EBV DNA positive. At baseline EBV positive patients had significantly higher disease activity (p=0.036) and the concentration of EBV DNA correlated significantly with DAS28 (rs=0.333, p=0.024). EBV DNA was detected in 3 of 22 CRA patients at study onset and in 8 of 16 in the follow-up samples. At follow-up EBV positive patients had significantly higher DAS28 (p=0.027) and the concentration of EBV DNA correlated significantly with DAS28 (rs=0.724, p=0.002). Only one of the healthy controls and none of the AOSD patients were positive for EBV DNA.

Conclusions: Active RA is associated with a lytic EBV infection which may have a role in the pathogenesis of RA.

MeSH terms

  • Adult
  • Aged
  • Antirheumatic Agents / therapeutic use
  • Arthritis, Rheumatoid / diagnosis*
  • Arthritis, Rheumatoid / drug therapy
  • Arthritis, Rheumatoid / epidemiology*
  • Arthritis, Rheumatoid / virology
  • Case-Control Studies
  • DNA, Viral / blood
  • DNA, Viral / genetics*
  • Epstein-Barr Virus Infections / blood
  • Epstein-Barr Virus Infections / diagnosis*
  • Epstein-Barr Virus Infections / epidemiology*
  • Epstein-Barr Virus Infections / virology
  • Female
  • Finland / epidemiology
  • Herpesvirus 4, Human / genetics*
  • Host-Pathogen Interactions
  • Humans
  • Male
  • Middle Aged
  • Polymerase Chain Reaction / methods*
  • Predictive Value of Tests
  • Prevalence
  • Risk Factors
  • Severity of Illness Index
  • Time Factors
  • Viral Load
  • Virus Activation

Substances

  • Antirheumatic Agents
  • DNA, Viral