Jules Weinhard , Johan Noble , Thomas Jouve , Paolo Malvezzi , Lionel Rostaing
{"title":"改善高免疫受试者肾脏移植的可及性:il -6通路阻断在去免疫方案中的作用是什么?","authors":"Jules Weinhard , Johan Noble , Thomas Jouve , Paolo Malvezzi , Lionel Rostaing","doi":"10.1016/j.nephro.2022.07.402","DOIUrl":null,"url":null,"abstract":"<div><h3>Background</h3><p>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.</p></div><div><h3>Methods</h3><p>Pubmed systematic review by using <em>MeSH</em> terms: tocilizumab, clazakizumab, interleukin-6 blockade, kidney transplantation, kidney graft and desensitization.</p></div><div><h3>Studies</h3><p>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.</p></div><div><h3>Conclusion</h3><p>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.</p></div>","PeriodicalId":51140,"journal":{"name":"Nephrologie & Therapeutique","volume":"18 7","pages":"Pages 577-583"},"PeriodicalIF":0.7000,"publicationDate":"2022-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Améliorer l’accès à la transplantation rénale des sujets hyperimmunisés : quelle place pour un blocage de la voie de l’IL-6 dans les protocoles de désimmunisation ?\",\"authors\":\"Jules Weinhard , Johan Noble , Thomas Jouve , Paolo Malvezzi , Lionel Rostaing\",\"doi\":\"10.1016/j.nephro.2022.07.402\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><h3>Background</h3><p>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.</p></div><div><h3>Methods</h3><p>Pubmed systematic review by using <em>MeSH</em> terms: tocilizumab, clazakizumab, interleukin-6 blockade, kidney transplantation, kidney graft and desensitization.</p></div><div><h3>Studies</h3><p>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.</p></div><div><h3>Conclusion</h3><p>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. 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Améliorer l’accès à la transplantation rénale des sujets hyperimmunisés : quelle place pour un blocage de la voie de l’IL-6 dans les protocoles de désimmunisation ?
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.
Studies
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.
Conclusion
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.
期刊介绍：
Organe d''expression de la Société de Néphrologie, de la Société Francophone de Dialyse et de la Société de Néphrologie Pédiatrique, Néphrologie et Thérapeutique a pour vocation de publier des textes en français dans le domaine de la Néphrologie, qu''il s''agisse d''actualisation des connaissances, de recommandations de bonne pratique clinique, de publications originales, ou d''informations sur la vie des trois sociétés fondatrices. La variété des thèmes abordés reflète la richesse de la Néphrologie, qu''il s''agisse d''aspects fondamentaux issus de la physiologie, de l''immunologie, de l''anatomo-pathologie, ou de la génétique, ou de sujets de néphrologie clinique, notamment ceux en rapport avec les thérapeutiques néphrologiques, transplantation, hémodialyse et dialyse péritonéale.
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