title: Epstein-Barr virus in peripheral blood is associated with response to rituximab therapy in rheumatoid arthritis patients.
abstract: Autoreactive B cells infected by Epstein-Barr virus (EBV) are suspected to be involved in the etiology of various human chronic autoimmune diseases. This motivated us to study the relationship between peripheral blood EBV load at baseline and treatment response to B cell-depleting therapy in rheumatoid arthritis (RA) patients. Thirty-five RA patients who started treatment with rituximab (RTX) in a routine clinical setting were assessed for baseline disease activity using disease activity score using 28 joint counts (DAS28) (erythrocyte sedimentation rate [ESR]). Treatment response was evaluated 3-7 months after RTX. EBV load in baseline whole blood (WB) samples was determined using quantitative PCR. EBV DNA was detected in 16/35 (46 %) of the WB samples. In these 16 EBV-positive patients, the median viral load was 3.15 (2.68-4.00) log copies/ml. Good/moderate European League Against Rheumatism (EULAR) response was observed in 16/16 of the EBV DNA-positive vs 13/19 EBV DNA-negative patients, p = 0.022. Significant response (DAS28 change >1.2) was observed in 14/16 of the EBV DNA-positive vs 10/19 EBV DNA-negative patients, p = 0.035. The decline in DAS28 after RTX was 2.10 (1.03-4. 78) in the EBV DNA-positive vs 1.47 (-0.7-4.70) in the EBV DNA-negative patients, p = 0.13. EBV load at baseline significantly correlated with change in DAS28 after RTX (τB = -0.261, p = 0.042). Our results suggest that the presence of EBV genome in WB could serve as a predictive marker to RTX therapy in RA.
authors.affiliation: Department of Medicine, Division of Rheumatology, Helsinki University Central Hospital, P.O. Box 372, FIN-00029 HUS, Helsinki, Finland, Heikki.Valleala@hus.fi.
authors.forename: Heikki
authors.initials: H
authors.lastname: Valleala
authors.forename: Markku J
authors.initials: MJ
authors.lastname: Kauppi
authors.forename: Vesa-Petteri
authors.initials: VP
authors.lastname: Kouri
authors.forename: Markku
authors.initials: M
authors.lastname: Korpela
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018501:Antirheumatic Agents / Q000627:therapeutic use*; D001172:Arthritis, Rheumatoid / Q000188:drug therapy* / Q000821:virology; D005260:Female; D004854:Herpesvirus 4, Human / Q000302:isolation & purification*; D006801:Humans; D008297:Male; D008875:Middle Aged; D000069283:Rituximab / Q000627:therapeutic use*; D016896:Treatment Outcome; D019562:Viral Load
chemical_list: D018501:Antirheumatic Agents; D000069283:Rituximab