Evaldo Favi , Donata Cresseri , Marta Perego , Masami Ikehata , Samuele Iesari , Maria Rosaria Campise , William Morello , Sara Testa , Viviana Sioli , Deborah Mattinzoli , Elena Longhi , Alessandro Del Gobbo , Giuseppe Castellano , Mariano Ferraresso
{"title":"联合应用抗补体成分 C5 eculizumab 和 2 型抗 CD20 obinutuzumab 治疗肾移植后早期抗体介导的排斥反应:概念验证。","authors":"Evaldo Favi , Donata Cresseri , Marta Perego , Masami Ikehata , Samuele Iesari , Maria Rosaria Campise , William Morello , Sara Testa , Viviana Sioli , Deborah Mattinzoli , Elena Longhi , Alessandro Del Gobbo , Giuseppe Castellano , Mariano Ferraresso","doi":"10.1016/j.clim.2024.110240","DOIUrl":null,"url":null,"abstract":"<div><p>Kidney transplant (KT) candidates with donor-specific antibodies (DSA) exhibit exceedingly high antibody-mediated rejection (ABMR) and allograft loss rates. Currently, treatment of ABMR remains an unmet clinical need. We report the use of the anti-C5 eculizumab and the type-2 anti-CD20 obinutuzumab in two patients with early ABMR. Eculizumab (900 mg IV) led to complete inhibition of the terminal complement cascade (unremarkable AP50 and CH50 activity) and prompt stoppage of complement-dependent antibody-mediated allograft injury (clearance of intra-graft C4d and C5b-9 deposition). Despite complement inhibition, obinutuzumab (1000 mg IV) determined full and long-lasting peripheral B-cell depletion, with significant reduction in all DSA. Graft function improved, remaining stable up to three years of follow-up. No signs of active ABMR and rebound DSA were detected. Obinutuzumab B-cell depletion and inhibition of DSA production were not affected by complement blockage. Further studies are needed to confirm the potential benefit of obinutuzumab in association with complement inhibitors.</p></div>","PeriodicalId":10392,"journal":{"name":"Clinical immunology","volume":null,"pages":null},"PeriodicalIF":4.5000,"publicationDate":"2024-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1521661624003498/pdfft?md5=885f2355a5b47e126bbb6f84fa7e5fa0&pid=1-s2.0-S1521661624003498-main.pdf","citationCount":"0","resultStr":"{\"title\":\"Sequential administration of anti-complement component C5 eculizumab and type-2 anti-CD20 obinutuzumab for the treatment of early antibody-mediated rejection after kidney transplantation: A proof of concept\",\"authors\":\"Evaldo Favi , Donata Cresseri , Marta Perego , Masami Ikehata , Samuele Iesari , Maria Rosaria Campise , William Morello , Sara Testa , Viviana Sioli , Deborah Mattinzoli , Elena Longhi , Alessandro Del Gobbo , Giuseppe Castellano , Mariano Ferraresso\",\"doi\":\"10.1016/j.clim.2024.110240\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><p>Kidney transplant (KT) candidates with donor-specific antibodies (DSA) exhibit exceedingly high antibody-mediated rejection (ABMR) and allograft loss rates. Currently, treatment of ABMR remains an unmet clinical need. We report the use of the anti-C5 eculizumab and the type-2 anti-CD20 obinutuzumab in two patients with early ABMR. Eculizumab (900 mg IV) led to complete inhibition of the terminal complement cascade (unremarkable AP50 and CH50 activity) and prompt stoppage of complement-dependent antibody-mediated allograft injury (clearance of intra-graft C4d and C5b-9 deposition). Despite complement inhibition, obinutuzumab (1000 mg IV) determined full and long-lasting peripheral B-cell depletion, with significant reduction in all DSA. Graft function improved, remaining stable up to three years of follow-up. No signs of active ABMR and rebound DSA were detected. Obinutuzumab B-cell depletion and inhibition of DSA production were not affected by complement blockage. Further studies are needed to confirm the potential benefit of obinutuzumab in association with complement inhibitors.</p></div>\",\"PeriodicalId\":10392,\"journal\":{\"name\":\"Clinical immunology\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":4.5000,\"publicationDate\":\"2024-05-09\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.sciencedirect.com/science/article/pii/S1521661624003498/pdfft?md5=885f2355a5b47e126bbb6f84fa7e5fa0&pid=1-s2.0-S1521661624003498-main.pdf\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Clinical immunology\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S1521661624003498\",\"RegionNum\":3,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"IMMUNOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Clinical immunology","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S1521661624003498","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"IMMUNOLOGY","Score":null,"Total":0}
Sequential administration of anti-complement component C5 eculizumab and type-2 anti-CD20 obinutuzumab for the treatment of early antibody-mediated rejection after kidney transplantation: A proof of concept
Kidney transplant (KT) candidates with donor-specific antibodies (DSA) exhibit exceedingly high antibody-mediated rejection (ABMR) and allograft loss rates. Currently, treatment of ABMR remains an unmet clinical need. We report the use of the anti-C5 eculizumab and the type-2 anti-CD20 obinutuzumab in two patients with early ABMR. Eculizumab (900 mg IV) led to complete inhibition of the terminal complement cascade (unremarkable AP50 and CH50 activity) and prompt stoppage of complement-dependent antibody-mediated allograft injury (clearance of intra-graft C4d and C5b-9 deposition). Despite complement inhibition, obinutuzumab (1000 mg IV) determined full and long-lasting peripheral B-cell depletion, with significant reduction in all DSA. Graft function improved, remaining stable up to three years of follow-up. No signs of active ABMR and rebound DSA were detected. Obinutuzumab B-cell depletion and inhibition of DSA production were not affected by complement blockage. Further studies are needed to confirm the potential benefit of obinutuzumab in association with complement inhibitors.
期刊介绍:
Clinical Immunology publishes original research delving into the molecular and cellular foundations of immunological diseases. Additionally, the journal includes reviews covering timely subjects in basic immunology, along with case reports and letters to the editor.