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Hypothesis for why rituximab treatment works

Posted by kasperezelius on 18 Nov 2012 at 15:25 GMT


As a result of the findings by Lerner et al. [1], one can speculate if the positive results of rituximab treatment in research by the oncologists Øystein Fluge and Olav Mella [2] (in at least some cases) may be due to a substantially reduced production of antibodies against EBV dUTPase and EBV DNA polymerase, when rituximab has killed a subset of B lymphocytes. One can assume that the level of these antibodies in the blood decreases over time due to a limited life span of the antibodies. This could explain that it takes a few months before the symptoms of the patient improves after rituximab treatment commences.

In the study of Fluge and Mella 2/3 of the patients got better during treatment with repeated infusions of rituximab [2]. Do these patients have ME-symptoms due to an immune reaction when antibodies react to viral proteins produced by Epstein-Barr virus? Can this be the reason that no auto-antibody yet has been found?

Maybe the Epstein-Barr virus dUTPase and DNA polymerase enzymes are produced by infected cells, as for example plasma cells, NK-cells, T-cells, myocytes or epithelial cells. One hypothesis could be that EBV residing inside myocytes start to produce these enzymes and that the immune system later reacts to them, which causes the typical symptom of post exertional malaise.

/Kasper Ezelius, M.Sc., Örebro, Sweden


1. Lerner AM, Ariza ME, Williams M, Jason L, Beqaj S, et al. (2012)
Antibody to Epstein-Barr Virus Deoxyuridine Triphosphate
Nucleotidohydrolase and Deoxyribonucleotide Polymerase in a Chronic
Fatigue Syndrome Subset. PLoS ONE 7(11): e47891.

2. Preliminary result of phase 2 study NCT01156909 at Haukeland University Hospital:
which is a continuation as a result of earlier postive result:
Fluge Ø, Bruland O, Risa K, Storstein A, Kristoffersen EK, et al. (2011) Benefit from B-Lymphocyte Depletion Using the Anti-CD20 Antibody Rituximab in Chronic Fatigue Syndrome. A Double-Blind and Placebo-Controlled Study. PLoS ONE 6(10): e26358. doi:10.1371/journal.pone.0026358

No competing interests declared.