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Alterations in B- and circulating T-follicular helper cell subsets in immune thrombotic thrombocytopenic purpura

Shin, Jin-Sup; Subhan, Maryam; Cambridge, Geraldine; Guo, Yanping; de Groot, Rens; Scully, Marie; Thomas, Mari; (2022) Alterations in B- and circulating T-follicular helper cell subsets in immune thrombotic thrombocytopenic purpura. Blood Advances 10.1182/bloodadvances.2022007025. (In press). Green open access

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Abstract

T follicular helper (Tfh) cells regulate development of antigen-specific B-cell immunity. We prospectively investigated B-cell and cTfh subsets in 45 immune TTP patients at presentation and longitudinally after rituximab (RTX). B-cell phenotype was altered at acute iTTP presentation with decreased transitional cells and postgerminal centre (post-GC) memory B cells and increased plasmablasts compared to healthy controls. A higher percentage of plasmablasts was associated with higher anti-ADAMTS13 IgG and lower ADAMTS13 antigen levels. In asymptomatic patients with ADAMTS13 relapse, there were increased naïve B cells and a global decrease in memory subsets, with a trend to increased plasmablasts. Total circulating Tfh (CD4+CXCR5+) and PD1+ Tfh cells were decreased at iTTP presentation. CD80 expression was decreased on IgD+ memory cells and double negative memory cells in acute iTTP. Longitudinal analysis: at repopulation after B cell depletion in de novo iTTP, post-GC and double negative memory B cells were reduced compared to pre-RTX. RTX did not cause alteration in cTfh frequency. The subsequent kinetics of naïve, transitional, memory B cells and plasmablasts did not differ significantly between patients who went on to relapse vs those who remained in remission. In summary, acute iTTP is characterised by dysregulation of B- and cTfh-cell homeostasis with depletion of post-GC memory cells and cTfh cells and increased plasmablasts. Changes in CD80 expression on B cells further suggest altered interactions with T cells.

Type: Article
Title: Alterations in B- and circulating T-follicular helper cell subsets in immune thrombotic thrombocytopenic purpura
Location: United States
Open access status: An open access version is available from UCL Discovery
DOI: 10.1182/bloodadvances.2022007025
Publisher version: https://doi.org/10.1182/bloodadvances.2022007025
Language: English
Additional information: This version is the author accepted manuscript. For information on re-use, please refer to the publisher's terms and conditions.
UCL classification: UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine > Inflammation
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > Institute of Cardiovascular Science > Pre-clinical and Fundamental Science
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > Institute of Cardiovascular Science
URI: https://discovery.ucl.ac.uk/id/eprint/10148417
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