Research ArticleRheumatoid Arthritis

A Plasmablast Biomarker for Nonresponse to Antibody Therapy to CD20 in Rheumatoid Arthritis

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Science Translational Medicine  21 Sep 2011:
Vol. 3, Issue 101, pp. 101ra92
DOI: 10.1126/scitranslmed.3002432

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A Molecular Magic Eight Ball

Ever wish you could predict the future? From children’s toys to psychic consultants, there’s an entire industry devoted to providing people with insight into upcoming events. This desire for precognition extends to clinical medicine—both doctors and patients wish they could predict whether a treatment will work for a particular disease in a particular patient. Thus, the search for biomarkers was born. However, many studies that claim to identify “biomarkers” have as little experimental validation as a late-night TV psychic, making the truly validated biomarker a rare gem. Owczarczyk et al. now develop such a predictor for nonresponsiveness to anti-CD20 antibody therapy for rheumatoid arthritis.

Rituximab and ocrelizumab are therapeutic antibodies that bind to CD20 on the surface of effector and memory B cells, causing them to be depleted from the circulation. These antibodies can be helpful to rheumatoid arthritis patients who don’t fare well with more general antirheumatic drugs, such as nonsteroidal anti-inflammatory drugs, and disease-modifying antirheumatic drugs, such as hydroxychloroquine, sulfasalazine, leflunomide, or methotrexate. But not all patients respond to these expensive targeted biologics. Owczarczyk et al. observed that rheumatoid arthritis patients who don’t respond to anti-CD20 antibodies had elevated amounts of IgJ mRNA, a marker for antibody-secreting plasmablasts. They then performed prospective testing of IgJ mRNA concentrations in one ocrelizumab and two rituximab patient cohorts and found that this marker could predict nonresponse to anti-CD20 antibody therapy. Moreover, a combination mRNA biomarker, IgJhiFCRL5lo, improved test performance over IgJhi alone. Will these biomarkers also be useful in stratifying response rates in other diseases in which anti-CD20 antibody therapy has shown clinical activity such as relapsing-remitting multiple sclerosis and ANCA-associated vasculitis? Cannot predict now. Ask again later.

Footnotes

  • * Present address: Department of Oncology, University College London Hospitals NHS Foundation Trust, 250 Euston Road, London NW1 2PG, UK.

  • These authors contributed equally to this work.

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