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Elevated Epstein-Barr Virus Load Found in Rheumatoid Arthritis Cases

Patients with rheumatoid arthritis have almost 10 times the Epstein-Barr virus (EBV) load in peripheral blood mononuclear cells (PBMCs) of healthy individuals, according to new findings.

Nathalie Balandraud, M.D., of INSERM and colleagues developed an assay of EBV DNA using a real-time quantitative polymerase chain reaction (PCR) with fluorescent probes, and found that EBV DNA in peripheral blood could be detected and quantified in approximately 90% of rheumatoid arthritis (RA) patients, those with other types of inflammatory conditions, and normal controls.

The investigators analysed blood samples provided by 84 RA patients, 69 normal controls, and 22 patients with inflammatory conditions other than RA. The latter group consisted of 5 patients with ankylosing spondylitis, 6 psoriatic arthritis patients, 2 Behcet's disease patients, 2 Sjögren's syndrome patients, 2 patients with undifferentiated arthritis, 1 polymyalgia rheumatica patient, 1 patient with periodic fever, and 1 patient with ulcerative colitis and arthritis.

A 214-bp segment from the highly conserved long internal repeat region 1 of EBV was amplified by real time PCR with fluorescein probe. Fluorescence was plotted against the number of cycles of PCR. Investigators calculated data using the fit-points method of analysis.

While EBV load was significantly higher for RA patients in comparison to non-RA patients and normal controls, no correlation was found between level of disease activity and EBV load in RA patients.

Additionally, no effect was observed on EBV load in RA patients as the result of RA treatment, or for factors such as age at diagnosis, disease duration, patient gender, or rheumatoid factor status.

Unexpectedly, researchers found that HLA-DR genes did not actively play a role in determining EBV load in either RA patients or controls, although previous study results suggest a possible association of EBV the HLA-DR4/DR1 background on which RA develops.

Concluding that EBV is an ideal candidate to cause chronic immune complex disease, the investigators said clinicians should consider anti-EBV antibody responses as one of the chronic autoantibody responses that are most relevant to the development of RA.
Arthritis Rheum 2003 May;48:5:1223-8. "Epstein-Barr virus load in the peripheral blood of patients with rheumatoid arthritis: Accurate quantification using real-time polymerase chain reaction"

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