Article ; Online: Effect of Optimized Immunosuppression (Including Rituximab) on Anti-Donor Alloresponses in Patients With Chronically Rejecting Renal Allografts.
2020 Volume 11, Page(s) 79
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 ...
| 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. |
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| MeSH term(s) | Adult ; B-Lymphocytes/immunology ; Female ; Graft Rejection/drug therapy ; Graft Rejection/therapy ; Graft Survival/drug effects ; Graft Survival/immunology ; Histocompatibility ; Humans ; Immunosuppression ; Immunosuppressive Agents/pharmacology ; Isoantibodies ; Kidney ; Kidney Transplantation ; Male ; Middle Aged ; Rituximab/pharmacology ; Tissue Donors |
| Chemical Substances | Immunosuppressive Agents ; Isoantibodies ; Rituximab (4F4X42SYQ6) |
| Language | English |
| Publishing date | 2020-02-05 |
| Publishing country | Switzerland |
| Document type | Case Reports ; Clinical Trial ; Journal Article ; Multicenter Study ; Randomized Controlled Trial ; Research Support, Non-U.S. Gov't |
| ZDB-ID | 2606827-8 |
| ISSN | 1664-3224 ; 1664-3224 |
| ISSN (online) | 1664-3224 |
| ISSN | 1664-3224 |
| DOI | 10.3389/fimmu.2020.00079 |
| Database | MEDical Literature Analysis and Retrieval System OnLINE |
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