Cytometry by time-of-flight immunophenotyping identifies a blood Sjögren's signature correlating with disease activity and glandular inflammation - 03/06/16
, Saida Boudaoud, MSc b, c, ∗, Scott Haskett, MSc a, ∗, Taylor L. Reynolds, DVM, PhD a, ∗, Gaetane Nocturne, MD, PhD b, c, d, Elizabeth Norton, BSc a, Xueli Zhang, BSc a, Myrtha Constant, BSc a, Daniel Park, MSc a, Wenting Wang, PhD a, Thierry Lazure, MD b, c, d, Christine Le Pajolec, MD d, Ayla Ergun, PhD a, Xavier Mariette, MD, PhD b, c, d, ‡Abstract |
Background |
Mass cytometry has recently emerged as a promising tool for clinical research. However, few studies have demonstrated its benefit for patient stratification and biomarker identification. Primary Sjögren's syndrome (pSS) is a prototype of chronic autoimmune disease, the pathogenesis of which remains unclear and for which treatment does not exist.
Objective |
This observational case-control study was designed to discover new cellular biomarkers and therapeutic targets in patients with pSS.
Methods |
Forty-nine patients with pSS and 45 control subjects were enrolled for clinical evaluation and mass cytometry quantification of 34 protein markers in blood. For a third of these subjects, matched labial salivary gland biopsy specimens were also analyzed by mass cytometry and immunohistochemistry.
Results |
In salivary gland biopsy specimens from patients with pSS, we identified a high number of activated CD8+ T cells, terminally differentiated plasma cells, and activated epithelial cells, pointing to new pathogenic mechanisms for future clinical intervention. In blood, we identified a 6-cell disease signature defined by decreased numbers of CD4 and memory B lymphocytes, decreased plasmacytoid dendritic cell numbers, and increased representation of activated CD4 and CD8 T cells and plasmablasts. These blood cellular components correlated with clinical parameters and, when taken together, clustered patients into subsets with distinct disease activity and glandular inflammation.
Conclusion |
This first application of mass cytometry to a well-stratified clinical cohort and small biopsy tissues establishes the benefits of such an approach for the discovery of new biomarkers and therapeutic targets. Similar high-dimensional immunophenotyping strategies could be implemented in longitudinal and interventional clinical settings in this and other disease areas.
Le texte complet de cet article est disponible en PDF.Graphical abstract |
Key words : Sjögren's syndrome, autoimmunity, mass cytometry, cytometry by time-of-flight, immunophenotyping, patient stratification, biomarker discovery, therapeutic target
Abbreviations used : AECG, AID, Bm, CyTOF, DMEM, ESSDAI, FS, IHC, LASSO, LSG, MXA, NK, pDC, pSS, RF, SSA, SSB
Plan
| Supported by an unrestricted grant (UPSud/SAIC N 97731) from Biogen to Université Paris-Sud. |
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| Disclosure of potential conflict of interest: M. Mingueneau is an employee of Biogen. S. Boudaoud received a grant from Biogen and is an employee of INSERM. S. Haskett is an employee of Biogen. T. L. Reynolds is an employee of Biogen. G. Nocturne has received a grant from Biogen. E. Norton is an employee of Biogen. X. Zhang is an employee of Biogen. M. Constant is an employee of Biogen. D. Park is an employee of Biogen. W. Wang is an employee and holds stock in Biogen. T. Lazure is an employee of Assitance Publique Hopitaux de Paris. A. Ergun is an employee of Biogen. X. Mariette received a grant from Biogen and provided consultancy for Biogen. The rest of the authors declare that they have no relevant conflicts of interest. |
Vol 137 - N° 6
P. 1809 - juin 2016 Retour au numéro
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