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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

Laura, Magil and Marsilio, Adriani and Véronique, Berthou and Keguan, Chen and Aude, Gleizes and Salima, Hacein-Bey-Abina and Agnes, Hincelin-Mery and Xavier, Mariette and Marc, Pallardy and Spindeldreher, Sebastian and Natacha, Szely and David, Isenberg and Jessica, Manson and 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

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