Low Percentage of Signal Regulatory Protein α/β
| Autor: | Magill, Laura, Adriani, Marsilio, Berthou, Véronique, 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 |
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| Rok vydání: | 2018 |
| Předmět: |
rheumatoid arthritis
Adult Male Immunology Receptors Cell Surface immunogenicity Arthritis Rheumatoid Drug Hypersensitivity memory B cells Humans Lymphocyte Count Prospective Studies Receptors Immunologic Neural Cell Adhesion Molecules Original Research Aged B cells B-Lymphocytes Tumor Necrosis Factor-alpha SIRP Adalimumab anti-TNF Middle Aged Prognosis Antigens Differentiation anti-drug antibodies Cross-Sectional Studies Antirheumatic Agents Female Immunologic Memory Biomarkers |
| Zdroj: | Frontiers in Immunology |
| ISSN: | 1664-3224 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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