Abstract：
BACKGROUND: Desensitization allows kidney transplantation for HLA highly sensitized subjects. Due to the central role of IL-6 in immunological response, tocilizumab (monoclonal antibody directed against IL-6 receptor) could probably improve desensitization efficacy.
METHODS: Pubmed systematic review by using MeSH terms: tocilizumab, clazakizumab, interleukin-6 blockade, kidney transplantation, kidney graft and desensitization.
METHODS: IL-6 plays a role in humoral response (plasmocyte differentiation induced by lymphocyte T, IL-21 secretion) as well as in cellular response (differentiation of LT Th17 rather than T reg). In desensitization field, tocilizumab was first studied as second-line treatment after failing of standard-of-care (apheresis, rituximab ± IgIV). Recent study showed that tocilizumab as a monotherapy attenuated anti-HLA antibodies rates but was not sufficient to allow transplantation. However, lymphocyte immunophenotyping showed that tocilizumab hindered B cells maturation. Thereby, tocilizumab could improve long-term efficacy of desensitization, by limiting the anti-HLA rebound and so avoiding antibody-mediated rejection. This hypothesis is supported by a recent study which used clazakizumab (monoclonal antibody directed against IL-6) in association with standard-of-care. In that study, clazakizumab was continued after kidney transplantation. Results were encouraging because 9/10 patients were transplanted and there was no donor-specific antibody at 6 months post-transplantation.
CONCLUSIONS: IL-6 pathway blockade as a monotherapy fails to desensitize HLA highly sensitized kidney transplant candidates. In association with standard-of-care, it does not seem to significatively improve kidney allograft access (short-term efficacy) vs. standard-of-care only. However, it could improve long-term prognosis of HLA incompatible transplantation by orienting the response towards a tolerogenic profile, by hindering B-cell maturation and, thereby, avoiding DSA rebounds after transplantation. This hypothesis needs to be proven by further studies.
METHODS: Pubmed systematic review by using MeSH terms: tocilizumab, clazakizumab, interleukin-6 blockade, kidney transplantation, kidney graft and desensitization.
METHODS: IL-6 plays a role in humoral response (plasmocyte differentiation induced by lymphocyte T, IL-21 secretion) as well as in cellular response (differentiation of LT Th17 rather than T reg). In desensitization field, tocilizumab was first studied as second-line treatment after failing of standard-of-care (apheresis, rituximab ± IgIV). Recent study showed that tocilizumab as a monotherapy attenuated anti-HLA antibodies rates but was not sufficient to allow transplantation. However, lymphocyte immunophenotyping showed that tocilizumab hindered B cells maturation. Thereby, tocilizumab could improve long-term efficacy of desensitization, by limiting the anti-HLA rebound and so avoiding antibody-mediated rejection. This hypothesis is supported by a recent study which used clazakizumab (monoclonal antibody directed against IL-6) in association with standard-of-care. In that study, clazakizumab was continued after kidney transplantation. Results were encouraging because 9/10 patients were transplanted and there was no donor-specific antibody at 6 months post-transplantation.
CONCLUSIONS: IL-6 pathway blockade as a monotherapy fails to desensitize HLA highly sensitized kidney transplant candidates. In association with standard-of-care, it does not seem to significatively improve kidney allograft access (short-term efficacy) vs. standard-of-care only. However, it could improve long-term prognosis of HLA incompatible transplantation by orienting the response towards a tolerogenic profile, by hindering B-cell maturation and, thereby, avoiding DSA rebounds after transplantation. This hypothesis needs to be proven by further studies.
摘要：
背景：脱敏允许对HLA高度致敏的受试者进行肾移植。由于IL-6在免疫反应中的核心作用，tocilizumab(针对IL-6受体的单克隆抗体)可能可以提高脱敏疗效.
方法：使用MeSH术语发布系统评价：托珠单抗，clazakizumab,白细胞介素-6阻断，肾移植,肾移植和脱敏。
方法：IL-6在体液反应中起作用（淋巴细胞T诱导的浆细胞分化，IL-21分泌）以及细胞反应（LTTh17而不是Treg的分化）。在脱敏领域，托珠单抗在标准治疗失败后首次作为二线治疗进行研究(单采术，利妥昔单抗±IgIV）。最近的研究表明，托珠单抗作为单一疗法降低了抗HLA抗体的发生率，但不足以允许移植。然而,淋巴细胞免疫分型显示托珠单抗阻碍了B细胞的成熟.因此，托珠单抗可以提高脱敏的长期疗效，通过限制抗HLA反弹，从而避免抗体介导的排斥反应。这一假设得到了最近的一项研究的支持，该研究使用了clazakizumab（针对IL-6的单克隆抗体）与标准护理相结合。在那项研究中,肾移植后继续使用clazakizumab.结果令人鼓舞，因为9/10的患者被移植，并且在移植后6个月没有供体特异性抗体。
结论：IL-6通路阻断作为单一疗法未能使HLA高度致敏的肾移植候选物脱敏。与护理标准相关，它似乎没有显着改善肾脏同种异体移植的访问（短期疗效）与仅标准护理。然而,它可以通过将反应定向为耐受原谱来改善HLA不相容移植的长期预后，通过阻碍B细胞成熟，因此，避免移植后DSA反弹。这一假设需要进一步的研究来证明。
方法：使用MeSH术语发布系统评价：托珠单抗，clazakizumab,白细胞介素-6阻断，肾移植,肾移植和脱敏。
方法：IL-6在体液反应中起作用（淋巴细胞T诱导的浆细胞分化，IL-21分泌）以及细胞反应（LTTh17而不是Treg的分化）。在脱敏领域，托珠单抗在标准治疗失败后首次作为二线治疗进行研究(单采术，利妥昔单抗±IgIV）。最近的研究表明，托珠单抗作为单一疗法降低了抗HLA抗体的发生率，但不足以允许移植。然而,淋巴细胞免疫分型显示托珠单抗阻碍了B细胞的成熟.因此，托珠单抗可以提高脱敏的长期疗效，通过限制抗HLA反弹，从而避免抗体介导的排斥反应。这一假设得到了最近的一项研究的支持，该研究使用了clazakizumab（针对IL-6的单克隆抗体）与标准护理相结合。在那项研究中,肾移植后继续使用clazakizumab.结果令人鼓舞，因为9/10的患者被移植，并且在移植后6个月没有供体特异性抗体。
结论：IL-6通路阻断作为单一疗法未能使HLA高度致敏的肾移植候选物脱敏。与护理标准相关，它似乎没有显着改善肾脏同种异体移植的访问（短期疗效）与仅标准护理。然而,它可以通过将反应定向为耐受原谱来改善HLA不相容移植的长期预后，通过阻碍B细胞成熟，因此，避免移植后DSA反弹。这一假设需要进一步的研究来证明。
