A distinct plasmablast and naïve B-cell phenotype in primary immune thrombocytopenia
| Autor: | Drew Provan, Shaun M. Flint, Robert B Henderson, Adele Gibson, Geoff Lucas, Raghava Nandigam, Caroline O. S. Savage, Adrian C. Newland, Louise Taylor |
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| Jazyk: | angličtina |
| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Adult Blood Platelets Male Naive B cell Population Plasma Cells B-Lymphocyte Subsets chemical and pharmacologic phenomena Plasma cell Article Immunophenotyping 03 medical and health sciences Young Adult 0302 clinical medicine Antigen T-Lymphocyte Subsets hemic and lymphatic diseases B-Cell Activating Factor medicine Humans B-cell activating factor education Autoantibodies education.field_of_study B-Lymphocytes Purpura Thrombocytopenic Idiopathic biology business.industry Autoantibody Peripheral tolerance Hematology Middle Aged 030104 developmental biology medicine.anatomical_structure Cross-Sectional Studies Phenotype Case-Control Studies Immunology biology.protein Female Antibody business Biomarkers 030215 immunology |
| Popis: | Primary immune thrombocytopenia is an autoimmune disorder in which platelet destruction is a consequence of both B- and T-cell dysregulation. Flow cytometry was used to further characterize the B- and T-cell compartments in a cross-sectional cohort of 26 immune thrombocytopenia patients including antiplatelet antibody positive (n=14) and negative (n=12) patients exposed to a range of therapies, and a cohort of matched healthy volunteers. Markers for B-cell activating factor and its receptors, relevant B-cell activation markers (CD95 and CD21) and markers for CD4(+) T-cell subsets, including circulating T-follicular helper-like cells, were included. Our results indicate that an expanded population of CD95(+) naive B cells correlated with disease activity in immune thrombocytopenia patients regardless of treatment status. A population of CD21-naive B cells was specifically expanded in autoantibody-positive immune thrombocytopenia patients. Furthermore, the B-cell maturation antigen, a receptor for B-cell activating factor, was consistently and strongly up-regulated on plasmablasts from immune thrombocytopenia patients. These observations have parallels in other autoantibody-mediated diseases and suggest that loss of peripheral tolerance in naive B cells may be an important component of immune thrombocytopenia pathogenesis. Moreover, the B-cell maturation antigen represents a potential target for plasma cell directed therapies in immune thrombocytopenia. |
| Databáze: | OpenAIRE |
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