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

T follicular helper (Tfh) cells regulate development of antigen-specific B-cell immunity. We prospectively investigated B-cell and circulating Tfh (cTfh) cell subsets in 45 patients with immune thrombotic thrombocytopenic purpura (iTTP) at presentation and longitudinally after rituximab (RTX). B-cell phenotype was altered at acute iTTP presentation with decreased transitional cells and post-germinal center (post-GC) memory B cells and increased plasmablasts compared with 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. At repopulation after B-cell depletion in de novo iTTP, post-GC and double-negative memory B cells were reduced compared with pre-RTX. RTX did not cause alteration in cTfh cell 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 characterized 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.