RESEARCH - Epstein-Barr virus in bone marrow of RA patients predicts response to rituximab

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Rheumatology Advance Access first published online on June 14, 2010

Rheumatology, doi:10.1093/rheumatology/keq159

Epstein–Barr virus in bone marrow of rheumatoid arthritis patients

predicts response to rituximab treatment

Mattias Magnusson1, Mikael Brisslert1, Kiandoht Zendjanchi1, Magnus

Lindh2 and I. Bokarewa1

1Department of Rheumatology and Inflammation Research and 2Department

of Virology, Sahlgrenska University Hospital, Göteborg, Sweden.

Abstract

Objectives.

Viruses may contribute to RA. This prompted us to monitor viral load

and response to anti-CD20 therapy in RA patients.

Methods.

Blood and bone marrow from 35 RA patients were analysed for CMV, EBV,

HSV-1, HSV-2, parvovirus B19 and polyomavirus using real-time PCR

before and 3 months after rituximab (RTX) treatment and related to the

levels of autoantibodies and B-cell depletion. Clinical response to

RTX was defined as decrease in the 28-joint disease activity score

(DAS-28) >1.3 at 6 months.

Results.

Before RTX treatment, EBV was identified in 15 out of 35 patients

(EBV-positive group), of which 4 expressed parvovirus. Parvovirus was

further detected in eight patients (parvo-positive group). Twelve

patients were negative for the analysed viruses. Following RTX, EBV

was cleared, whereas parvovirus was unaffected. Eighteen patients were

responders, of which 12 were EBV positive. The decrease in the DAS-28

was significantly higher in EBV-positive group compared with

parvo-positive group (P = 0.002) and virus-negative patients (P =

0.04). Most of EBV-negative patients that responded to RTX (75%)

required retreatment within the following 11 months compared with only

8% of responding EBV-positive patients. A decrease of RF, Ig-producing

cells and CD19+ B cells was observed following RTX but did not

distinguish between viral infections. However, EBV-infected patients

had significantly higher levels of Fas-expressing B cells at baseline

as compared with EBV-negative groups.

Conclusions.

EBV and parvovirus genomes are frequently found in bone marrow of RA

patients. The presence of EBV genome was associated with a better

clinical response to RTX. Thus, presence of EBV genome may predict

clinical response to RTX.

http://rheumatology.oxfordjournals.org/cgi/content/abstract/keq159v2?papetoc

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