title: A distinct plasmablast and naïve B-cell phenotype in primary immune thrombocytopenia.
abstract: 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.
authors.affiliation: Immunoinflammation TAU, GSK, Stevenage, London, UK Department of Medicine, University of Cambridge, London, UK.
authors.forename: Shaun M
authors.initials: SM
authors.lastname: Flint
authors.affiliation: Immunoinflammation TAU, GSK, Stevenage, London, UK.
authors.forename: Adele
authors.initials: A
authors.lastname: Gibson
authors.affiliation: Histocompatibility and Immunogenetics Laboratory, NHS Blood & Transplant, London, UK.
authors.forename: Geoff
authors.initials: G
authors.lastname: Lucas
authors.affiliation: Department of Haematology, Royal London Hospital, London, UK.
authors.forename: Raghava
authors.initials: R
authors.lastname: Nandigam
authors.affiliation: Department of Haematology, Royal London Hospital, London, UK.
authors.forename: Louise
authors.initials: L
authors.lastname: Taylor
authors.affiliation: Department of Haematology, Royal London Hospital, London, UK.
authors.forename: Drew
authors.initials: D
authors.lastname: Provan
authors.affiliation: Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, UK.
authors.forename: Adrian C
authors.initials: AC
authors.lastname: Newland
authors.affiliation: Immunoinflammation TAU, GSK, Stevenage, London, UK.
authors.forename: Caroline O
authors.initials: CO
authors.lastname: Savage
authors.affiliation: Immunoinflammation TAU, GSK, Stevenage, London, UK robbie.b.henderson@gsk.com.
authors.forename: Robert B
authors.initials: RB
authors.lastname: Henderson
mesh_terms: D000328:Adult; D001323:Autoantibodies / Q000097:blood / Q000276:immunology; D053264:B-Cell Activating Factor / Q000097:blood / Q000378:metabolism; D016175:B-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D001402:B-Lymphocytes / Q000276:immunology* / Q000378:metabolism*; D015415:Biomarkers; D001792:Blood Platelets / Q000276:immunology; D016022:Case-Control Studies; D003430:Cross-Sectional Studies; D005260:Female; D006801:Humans; D016130:Immunophenotyping; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D010950:Plasma Cells / Q000276:immunology* / Q000378:metabolism* / Q000473:pathology; D016553:Purpura, Thrombocytopenic, Idiopathic / Q000175:diagnosis / Q000276:immunology* / Q000378:metabolism* / Q000628:therapy; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism; D055815:Young Adult
chemical_list: D001323:Autoantibodies; D053264:B-Cell Activating Factor; D015415:Biomarkers