Prediction of severe rheumatoid arthritis using Epstein-Barr virus

One of the immunological abnormalities in patients with RA is increased synthesis of immunoglobulins (Ig) in cultures of Epstein-Barr virus (EBV-) stimulated lymphocytes. We set out to investigate whether this feature, seen early in the disease, associated with later severe RA. We studied prospectively 45 patients with recent onset RA and, 41 healthy individuals. From 0-6 months after admission, blood lymphocytes were cultured in the presence of EBV for 4 weeks and Ig in the supernatants were assayed. To assess the severity of disease, clinical, laboratory and radiological evaluations were performed every 6 months for 2 yr. The association of increased Ig production with the severity of RA was then analysed. During the follow-up period, 30 of the original 45 patients developed erosive disease. At onset, these 30 patients did not differ from the 15 with non-erosive disease when assessed by several parameters reflecting rheumatoid activity. However, EBV-induced production of Ig was significantly higher in the erosive compared with the non-erosive group of patients (P < 0.001). Using Ig synthesis, it was possible to identify a subgroup of 9-14 patients, depending on the isotype studied, who would later develop severe erosive disease (PVpos = 90-100%). These results show that high EBV-induced production of Ig early in RA associates with later severe disease, particularly with joint erosions. This feature identifies, with over 90% likelihood, the third of patients who will later develop most severe disease.