Immune responses following tocilizumab therapy to desensitize HLA‐sensitized kidney transplant candidates

摘要

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‐na?ve 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 na?ve 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.