Patterns of constitutively phosphorylated kinases in B cells are associated with disease severity in common variable immunodeficiency
Copyright © 2016 Elsevier Inc. All rights reserved.
Veröffentlicht in: | Clinical immunology (Orlando, Fla.). - 1999. - 175(2017) vom: 01. Feb., Seite 69-74 |
---|---|
1. Verfasser: | |
Weitere Verfasser: | , , , , , |
Format: | Online-Aufsatz |
Sprache: | English |
Veröffentlicht: |
2017
|
Zugriff auf das übergeordnete Werk: | Clinical immunology (Orlando, Fla.) |
Schlagworte: | Journal Article Research Support, Non-U.S. Gov't B cell Cell signaling Common variable immunodeficiency Constitutive phosphorylation Hierarchical clustering Phospho-flow cytometry Receptors, Antigen, B-Cell Phosphotransferases |
Zusammenfassung: | Copyright © 2016 Elsevier Inc. All rights reserved. Patients with common variable immunodeficiency (CVID) constitute a clinically and immunologically heterogeneous group characterized by B-cell dysfunction with hypogammaglobulinemia and defective immunoglobulin class switch of unknown etiology. Current classification systems are insufficient to achieve precise disease management. Characterization of signaling pathways essential for B-cell differentiation and class switch could provide new means to stratify patients. We evaluated constitutive and induced signaling by phospho-specific flow cytometry in 26 CVID patients and 18 healthy blood donors. Strong responses were induced both in CVID and healthy donor B cells upon activation. In contrast, constitutive phosphorylation levels of STAT3,-5,-6, Erk, PLC-γ and Syk were significantly increased in CVID B cells only. Hierarchical clustering revealed a subgroup of CVID patients with elevated constitutive phosphorylation of Syk and PLC-γ. All these patients had non-infectious complications, indicating that a distinct phosphorylation pattern of kinases in B cells identifies a clinically important subgroup of CVID patients |
---|---|
Beschreibung: | Date Completed 05.06.2017 Date Revised 06.02.2018 published: Print-Electronic Citation Status MEDLINE |
ISSN: | 1521-7035 |
DOI: | 10.1016/j.clim.2016.11.014 |