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Effect of Optimized Immunosuppression (Including Rituximab) on Anti-Donor Alloresponses in Patients With Chronically Rejecting Renal Allografts

Authors :
Kin Yee Shiu
Dominic Stringer
Laura McLaughlin
Olivia Shaw
Paul Brookes
Hannah Burton
Hannah Wilkinson
Harriet Douthwaite
Tjir-Li Tsui
Adam Mclean
Rachel Hilton
Sian Griffin
Colin Geddes
Simon Ball
Richard Baker
Candice Roufosse
Catherine Horsfield
Anthony Dorling
Source :
Frontiers in Immunology, Vol 11 (2020)
Publication Year :
2020
Publisher :
Frontiers Media S.A., 2020.

Abstract

RituxiCAN-C4 combined an open-labeled randomized controlled trial (RCT) in 7 UK centers to assess whether rituximab could stabilize kidney function in patients with chronic rejection, with an exploratory analysis of how B cell-depletion influenced T cell anti-donor responses relative to outcome. Between January 2007 and March 2015, 59 recruits were enrolled after screening, 23 of whom consented to the embedded RCT. Recruitment was halted when in a pre-specified per protocol interim analysis, the RCT was discovered to be significantly underpowered. This report therefore focuses on the exploratory analysis, in which we confirmed that when B cells promoted CD4+ anti-donor IFNγ production assessed by ELISPOT, this associated with inferior clinical outcome; these patterns were inhibited by optimized immunosuppression but not rituximab. B cell suppression of IFNγ production, which associated with number of transitional B cells and correlated with slower declines in kidney function was abolished by rituximab, which depleted transitional B cells for prolonged periods. We conclude that in this patient population, optimized immunosuppression but not rituximab promotes anti-donor alloresponses associated with favorable outcomes.Clinical Trial Registration: Registered with EudraCT (2006-002330-38) and www.ClinicalTrials.gov, identifier: NCT00476164.

Details

Language :
English
ISSN :
16643224
Volume :
11
Database :
Directory of Open Access Journals
Journal :
Frontiers in Immunology
Publication Type :
Academic Journal
Accession number :
edsdoj.9ada6f057e794dd7ba43b83bcdef0472
Document Type :
article
Full Text :
https://doi.org/10.3389/fimmu.2020.00079