Laura, Magil, Marsilio, Adriani, Véronique, Berthou, Keguan, Chen, Aude, Gleizes, Salima, Hacein-Bey-Abina, Agnes, Hincelin-Mery, Xavier, Mariette, Marc, Pallardy, Spindeldreher, Sebastian, Natacha, Szely, David, Isenberg, Jessica, Manson, Elizabeth, Jury and Claudia, Mauri (2018) Low Percentage of Signal Regulatory Protein α/β+ Memory B Cells in Blood Predicts Development of Anti-drug Antibodies (ADA) in Adalimumab-Treated Rheumatoid Arthritis Patients. Frontiers in immunology, 9. ISSN 16643224

Abstract

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)α. By taking advantage of an immune-phenotyping platform, LEGENDScreen™, 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)α/β-expressing memory B cells in ADA+ vs. ADA- RA patients. We also assessed the predictive value of SIRPα/β expression in a longitudinal RA cohort prior to the initiation of adalimumab treatment. We show that a frequency of < 9.4% of SIRPα/β-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 SIRPα/β-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.

Item Type:	Article
Keywords:	adalimumab anti-drug antibodies anti-TNF B cells immunogenicity memory B cells rheumatoid arthritis SIRP
Date Deposited:	11 Jun 2019 00:45
Last Modified:	11 Jun 2019 00:45
URI:	https://oak.novartis.com/id/eprint/38102