A distinct plasmablast and naïve B-cell phenotype in primary immune thrombocytopenia

• Published in: Haematologica (Roma) Vol. 101; no. 6; pp. 698 - 706
• Main Authors: Flint, Shaun M, Gibson, Adele, Lucas, Geoff, Nandigam, Raghava, Taylor, Louise, Provan, Drew, Newland, Adrian C, Savage, Caroline O, Henderson, Robert B
• Format: Journal Article
• Language: English
• Published: Italy Ferrata Storti Foundation 01.06.2016
• Subjects: Adult; Autoantibodies - blood; Autoantibodies - immunology; B-Cell Activating Factor - blood; B-Cell Activating Factor - metabolism; B-Lymphocyte Subsets - immunology; B-Lymphocyte Subsets - metabolism; B-Lymphocyte Subsets - pathology; B-Lymphocytes - immunology; B-Lymphocytes - metabolism; Biomarkers; Blood Platelets - immunology; Case-Control Studies; Cross-Sectional Studies; Female; Humans; Immunophenotyping; Male; Middle Aged; Phenotype; Plasma Cells - immunology; Plasma Cells - metabolism; Plasma Cells - pathology; Purpura, Thrombocytopenic, Idiopathic - diagnosis; Purpura, Thrombocytopenic, Idiopathic - immunology; Purpura, Thrombocytopenic, Idiopathic - metabolism; Purpura, Thrombocytopenic, Idiopathic - therapy; T-Lymphocyte Subsets - immunology; T-Lymphocyte Subsets - metabolism; Young Adult
• ISSN: 0390-6078; 1592-8721
• DOI: 10.3324/haematol.2015.137273

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(+) naïve B cells correlated with disease activity in immune thrombocytopenia patients regardless of treatment status. A population of CD21-naïve 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 naïve 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.