Low Percentage of Signal Regulatory Protein alpha/beta(+) Memory B Cells in Blood Predicts Development of Anti-drug Antibodies (ADA) in Adalimumab-Treated Rheumatoid Arthritis Patients

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Magill, Laura | Adriani, Marsilio | Berthou, Veronique | Chen, Keguan | Gleizes, Aude | Hacein-Bey-Abina, Salima | Hincelin-Mery, Agnes | Mariette, Xavier | Pallardy, Marc | Spindeldreher, Sebastian | Szely, Natacha | Isenberg, David A. | Manson, Jessica J. | Jury, Elizabeth C. | Mauri, Claudia

Edité par CCSD ; Frontiers -

International audience. An important goal for personalized treatment is predicting response to a particular therapeutic. A drawback of biological treatment is immunogenicity and the development of antibodies directed against the drug [anti-drug antibodies (ADA)], which are associated with a poorer clinical outcome. Here we set out to identify a predictive biomarker that discriminates rheumatoid arthritis (RA) patients who are more likely to develop ADA in response to adalimumab, a human monoclonal antibody against tumor necrosis factor (TNF)alpha. By taking advantage of an immune-phenotyping platform, LEGENDScreen (TM), we measured the expression of 332 cell surface markers on B and T cells in a cross-sectional adalimumab-treated RA patient cohort with a defined ADA response. The analysis revealed seven differentially expressed markers (DEMs) between the ADA(+) and ADA(-) patients. Validation of the DEMs in an independent prospective European cohort of adalimumab treated RA patients, revealed a significant and consistent reduced frequency of signal regulatory protein (SIRP)alpha/beta-expressing memory B cells in ADA(+ )vs. ADA(-) RA patients. We also assessed the predictive value of SIRP alpha/beta-expression in a longitudinal RA cohort prior to the initiation of adalimumab treatment. We show that a frequency of <9.4% of SIRP alpha/beta-expressing memory B cells predicts patients that will develop ADA, and consequentially fail to respond to treatment, with a receiver operating characteristic (ROC) area under the curve (AUC) score of 0.92. Thus, measuring the frequency of SIRP alpha/beta-expressing memory B cells in patients prior to adalimumab treatment may be clinically useful to identify a subgroup of active RA subjects who are going to develop an ADA response and not gain substantial clinical benefit from this treatment.

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