Immune responses following tocilizumab therapy to desensitize HLA‐sensitized kidney transplant candidates. Issue 1 (23rd June 2021)

• Record Type: Journal Article
• Authors: Jouve, Thomas; Laheurte, Caroline; Noble, Johan; Weinhard, Jules; Daligault, Mélanie; Renaudin, Adeline; Naciri Bennani, Hamza; Masson, Dominique; Gravelin, Eléonore; Bugnazet, Mathilde; Bardy, Béatrice; Malvezzi, Paolo; Saas, Philippe; Rostaing, Lionel
• Is Part Of: American journal of transplantation. Volume 22:Issue 1(2022)
• Page Start: 71
• Page End: 84
• Publication Date: 2021-06-23
• Subjects: clinical research / practice -- desensitization -- kidney transplantation / nephrology -- kidney transplantation: living donor -- translational research / science; Transplantation of organs, tissues, etc -- Periodicals; 617.95
• DOI: 10.1111/ajt.16709
• Languages: English
• ISSNs: 1600-6135

Abstract

Abstract : Kidney transplant candidates (KTCs) who are HLA highly sensitized (calculated panel‐reactive alloantibodies >95%) have poor access to deceased kidney transplantation. In this single‐center prospective study, 13 highly sensitized desensitization‐naïve KTCs received IV tocilizumab (8 mg/kg) every 4 weeks. We evaluated tolerability as well as immune responses, that is, T cell, B cell, T follicular helper (Tfh) subsets, blood cytokines (IL‐6, soluble IL‐6 receptor‐sIL‐6R‐, IL‐21), blood chemokines (CXCL10, CXCL13), and anti‐HLA alloantibodies. Tocilizumab treatment was well‐tolerated except in one patient who presented spondylodiscitis, raising a note of caution. Regarding immune parameters, there were no significant changes of percentages of lymphocyte subsets, that is, CD3 +, CD3 + /CD4 +, CD3 + /CD8 + T cells, and NK cells. This was also the case for Tfh cell subsets, B cells, mature B cells, plasma cells, pre‐germinal center (GC) B cells, and post‐GC B cells, whereas we observed a significant increase in naïve B cells ( p = .02) and a significant decrease in plasmablasts ( p = .046) over the tocilizumab treatment course. CXCL10, CXCL13, IL‐21, total IgG, IgA, and IgM levels did not significantly change during tocilizumab therapy; conversely, there was a significant increase in IL‐6 levels ( p = .03) and a huge increase in sIL‐6R ( p = .00004). There was a marginal effect on anti‐HLA alloantibodies (class I and class II). To conclude in highly sensitized KTCs, tocilizumab as a monotherapy limited B cell maturation; however, it had almost no effect on anti‐HLA alloantibodies. Abstract : Tocilizumab, as a single desensitization agent before kidney transplantation, fails to reduce the HLA antibody burden but induces a B cell maturation defect.