PB0310 - Longitudinal kinetics of B-cell subsets in Immune Thrombotic Thrombocytopenic Purpura Patients: Relapses vs Remission

Sunday, July 10, 2022

6:30 PM – 7:30 PM

Location: Exhibition

Presentation Format: In-Person

Presenting Author(s)

Maryam Subhan

Clinical Research Fellow
University College London
London, England, United Kingdom

Co-Author(s)

JS

Jin-Sup Shin

Haematology Registrar
University College London Hospitals NHS Foundation Trust
London, England, United Kingdom
BC

Brian Craven

Clinical Research Fellow
University College London
London, England, United Kingdom
Rd

Rens de Groot

Senior Research Fellow
University College London
London, England, United Kingdom
YG

Yanping Guo

Flow Cytometry Translational Technology Platform Manager
Univsersity College London
London, England, United Kingdom
GC

Geraldine Cambridge

Professorial Research Associate
University College London
London, England, United Kingdom
Marie Scully, MD

Professor of Haemostasis and Thrombosis
Department of Haematology, University College London Hospitals, London, UK
London, England, United Kingdom
Mari Thomas, MD, PhD

Consultant Haematologist
University College Hospitals London NHS Foundation Trust
London, England, United Kingdom

Background: Risk of relapse in immune-mediated Thrombotic Thrombocytopenic Purpura (iTTP) is 30-50%. B-cell return following rituximab is not temporally associated with disease relapse.

Aims: We prospectively investigated changes in B-cell subsets in relation to clinical and laboratory parameters in iTTP patients longitudinally after anti-CD20 therapy for an acute iTTP episode or ADAMTS13 relapse (ADAMTS13 activity < 15%) until subsequent clinical or ADAMTS13 relapse, and compared to patients who remained in remission over an equivalent period.

Methods: Heparinized blood samples were collected from iTTP patients consented to the UK TTP Registry at presentation of acute episode or prior to elective rituximab, and thereafter at 3-6 monthly intervals. Flow cytometry on isolated PBMCs was performed on a Cytoflex-S cytometer using the mature B-cell ‘Bm1–Bm5’ classification to identify B-cell subsets based on co-expression of IgD and CD38 and analysed using FlowJo software.

Results: There were 10 patients in the relapse cohort (3 followed after an acute episode, 7 after elective rituximab) and 10 in the remission cohort (4 acute and 6 elective episodes at t=0). Median age was 51y (range 38-81) and 45.5y (21-68) respectively. One patient in each group did not achieve B-cell depletion (CD19+ count < 0.005x10^9/L). Time to B-cell return was similar: 8 months (4-13) in relapses vs 9 months in remission (5-15.5). All subsequent relapses were ADAMTS13 relapses and occurred at a median of 16 months (9-25).

Longitudinal analysis showed that in both groups B-cell return after rituximab develops along normal B-cell ontogeny. The 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.

Conclusion(s): No alterations in B-cell subsets were identified prior to a relapse, suggesting temporal relationships between B sub-populations cannot be used as a biomarker to better predict relapses.