Epstein-Barr virus in bone marrow of rheumatoid arthritis patients predicts response to rituximab treatment – Source: Rheumatology (Oxford), Jun 14, 2010

Objectives: Viruses may contribute to RA. This prompted us to monitor viral load and response to anti-CD20 therapy in RA patients. [The drug rituximab is an antibody against the protein CD20, found on the overactive B cells involved in the autoimmune activity of RA. In some patients, rituximab helps RA by depleting B cells.]

Methods: Blood and bone marrow from 35 RA patients were analysed for CMV (cytomegalovirus, a member of the herpes virus family), EBV (Epstein-Barr), HSV-1, HSV-2 (herpes simplex viruses), 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. [PCR – polymerase chain reaction – is a technique used to identify the presence of disease-causing viruses and/or bacteria.]

Clinical response to RTX was defined as decrease in the 28-joint disease activity score (DAS-28) of more than 1.3 at 6 months.


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.


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.

Source: Rheumatology, Jun 14, 2010. Magnusson M, Brisslert M, Zendjanchi K, Lindh M, Bokarewa MI. Department of Rheumatology and Inflammation Research and Department of Virology, Sahlgrenska University Hospital, Göteborg, Sweden.

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