High-content cytometry and transcriptomic biomarker profiling of human B-cell activation - 25/12/13
Abstract |
Background |
Primary antibody deficiencies represent the most prevalent, although very heterogeneous, group of inborn immunodeficiencies, with a puzzling complexity of cellular and molecular processes involved in disease pathogenesis.
Objective |
We aimed to study in detail the kinetics of CD40 ligand/IL-21–induced B-cell differentiation to define new biomarker sets for further research into primary antibody deficiencies.
Methods |
We applied high-content screening methods to monitor B-cell activation on the cellular (chip cytometry) and transcriptomic (RNA microarray) levels.
Results |
The complete activation process, including stepwise changes in protein and RNA expression patterns, entry into the cell cycle, proliferation and expression of activation-induced cytidine deaminase (AID), DNA repair enzymes, and post–class-switch expression of IgA and IgG, was successfully monitored during in vitro differentiation. We identified a number of unknown pathways engaged during B-cell activation, such as CXCL9/CXCL10 secretion by B cells. Finally, we evaluated a deduced set of biomarkers on a group of 18 patients with putative or proved intrinsic B-cell defects recruited from the European Society for Immunodeficiencies database and successfully predicted 2 AID defects and 1 DNA repair defect. Complete absence of class-switched B cells was a sensitive predictor of AID deficiency and should be further evaluated as a diagnostic biomarker.
Conclusion |
The biomarkers found in this study could be used to further study the complex process of B-cell activation and to understand conditions that lead to the development of primary antibody deficiencies.
Le texte complet de cet article est disponible en PDF.Key words : Primary immunodeficiency, primary antibody deficiency, B-cell immunology, chip cytometry
Abbreviations used : AID, CD40L, CSR, CVID, MACS, PID
Plan
Disclosure of potential conflict of interest: The authors declare that they have no relevant conflicts of interest. |
Vol 133 - N° 1
P. 172 - janvier 2014 Retour au numéroBienvenue sur EM-consulte, la référence des professionnels de santé.
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