Impact of Tocilizumab (Anti-IL-6R) Treatment on Immunoglobulins and Anti-HLA Antibodies in Kidney Transplant Patients with Chronic Antibody-Mediated Rejection.

Background. Chronic antibody-mediated rejection (cAMR) results in the majority of renal allograft losses. Currently, there are no approved therapies. We recently reported on clinical use of tocilizumab (TCZ) for treatment of cAMR in HLA-sensitized kidney transplant patients. IgG(1) and IgG(3) subclasses of IgG are potent effectors of complement- and antibody-dependent cellular cytotoxicity, which are critical mediators of AMR. Here, we examined the impact of TCZ treatment for cAMR on total IgG, IgG(1-4) subclasses, and anti-HLA-IgG (total and subclasses). Methods. Archived plasma obtained pre- and post-TCZ treatment (8 mg/kg, 6x, monthly) from 12 cAMR patients who failed standard of care treatment with intravenous immune globulin + rituximab with or without plasma exchange were tested for total IgG and IgG(1-4) by ELISA, anti-HLA-total IgG, IgG(3) and IgG(4), and donor-specific antibody by Luminex assay. Archived plasma from 14 cAMR patients treated with the standard of care were included as controls. Results. Total IgG and IgG(1-3) were significantly reduced post-TCZ, whereas no reduction was seen post-treatment in the control group. Of 11 patients, 8 (73%) showed reduction of anti-HLA-total IgG and IgG(3) post-TCZ, but this was not statistically significant. Conclusions. TCZ reduced total IgG and IgG(1-3) and anti-HLA-total IgG and IgG(3) levels, suggesting that TCZ suppresses Ig production in B cells nonspecifically, likely through inhibition of interleukin 6-mediated signaling to B cells and plasma cells. This may be a contributing factor for the beneficial effect of TCZ on cAMR observed in this patient population.