Case report: Eculizumab plus obinutuzumab induction in a deceased donor kidney transplant recipient with DEAP-HUS
The wide-spread use of the anti-complement component 5 monoclonal antibody (moAb) eculizumab has greatly reduced the incidence of relapsing atypical hemolytic uremic syndrome (aHUS) after kidney transplantation (KT). However, the optimal management of aHUS transplant candidates with anti-Complement...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2022-12-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2022.1073808/full |
| _version_ | 1798006480260038656 |
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| author | Evaldo Favi Evaldo Favi Paolo Molinari Carlo Alfieri Carlo Alfieri Giuseppe Castellano Giuseppe Castellano Mariano Ferraresso Mariano Ferraresso Donata Cresseri |
| author_facet | Evaldo Favi Evaldo Favi Paolo Molinari Carlo Alfieri Carlo Alfieri Giuseppe Castellano Giuseppe Castellano Mariano Ferraresso Mariano Ferraresso Donata Cresseri |
| author_sort | Evaldo Favi |
| collection | DOAJ |
| description | The wide-spread use of the anti-complement component 5 monoclonal antibody (moAb) eculizumab has greatly reduced the incidence of relapsing atypical hemolytic uremic syndrome (aHUS) after kidney transplantation (KT). However, the optimal management of aHUS transplant candidates with anti-Complement Factor H (CFH) antibodies remains debated. In these patients, the benefits of chronic eculizumab administration should be weighed against the risk of fatal infections, repeated hospital admissions, and excessive costs. We report the case of a 45-year-old female patient with CFHR1/CFHR3 homozygous deletion-associated aHUS who underwent deceased-donor KT despite persistently elevated anti-CFH antibody titers. As induction and aHUS prophylaxis, she received a combination of eculizumab and obinutuzumab, a humanized type 2 anti-CD20 moAb. The post-operative course was uneventful. After 1-year of follow-up, she is doing well with excellent allograft function, undetectable anti-CFH antibodies, sustained B-cell depletion, and no signs of aHUS activity. A brief review summarizing current literature on the topic is also included. Although anecdotal, our experience suggests that peri-operative obinutuzumab administration can block anti-CFH antibodies production safely and effectively, thus ensuring long-lasting protection from post-transplant aHUS relapse, at a reasonable cost. For the first time, we have demonstrated in vivo that obinutuzumab B-cell depleting properties are not significantly affected by eculizumab-induced complement inhibition. |
| first_indexed | 2024-04-11T12:56:29Z |
| format | Article |
| id | doaj.art-d9a63571d29b4a7d92f8db6c800ca01a |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-04-11T12:56:29Z |
| publishDate | 2022-12-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-d9a63571d29b4a7d92f8db6c800ca01a2022-12-22T04:23:04ZengFrontiers Media S.A.Frontiers in Immunology1664-32242022-12-011310.3389/fimmu.2022.10738081073808Case report: Eculizumab plus obinutuzumab induction in a deceased donor kidney transplant recipient with DEAP-HUSEvaldo Favi0Evaldo Favi1Paolo Molinari2Carlo Alfieri3Carlo Alfieri4Giuseppe Castellano5Giuseppe Castellano6Mariano Ferraresso7Mariano Ferraresso8Donata Cresseri9General Surgery and Kidney Transplantation, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Milan, ItalyDepartment of Clinical Sciences and Community Health, Università degli Studi di Milano, Milan, ItalyNephrology, Dialysis, and Transplantation, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Milan, ItalyDepartment of Clinical Sciences and Community Health, Università degli Studi di Milano, Milan, ItalyNephrology, Dialysis, and Transplantation, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Milan, ItalyDepartment of Clinical Sciences and Community Health, Università degli Studi di Milano, Milan, ItalyNephrology, Dialysis, and Transplantation, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Milan, ItalyGeneral Surgery and Kidney Transplantation, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Milan, ItalyDepartment of Clinical Sciences and Community Health, Università degli Studi di Milano, Milan, ItalyNephrology, Dialysis, and Transplantation, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Milan, ItalyThe wide-spread use of the anti-complement component 5 monoclonal antibody (moAb) eculizumab has greatly reduced the incidence of relapsing atypical hemolytic uremic syndrome (aHUS) after kidney transplantation (KT). However, the optimal management of aHUS transplant candidates with anti-Complement Factor H (CFH) antibodies remains debated. In these patients, the benefits of chronic eculizumab administration should be weighed against the risk of fatal infections, repeated hospital admissions, and excessive costs. We report the case of a 45-year-old female patient with CFHR1/CFHR3 homozygous deletion-associated aHUS who underwent deceased-donor KT despite persistently elevated anti-CFH antibody titers. As induction and aHUS prophylaxis, she received a combination of eculizumab and obinutuzumab, a humanized type 2 anti-CD20 moAb. The post-operative course was uneventful. After 1-year of follow-up, she is doing well with excellent allograft function, undetectable anti-CFH antibodies, sustained B-cell depletion, and no signs of aHUS activity. A brief review summarizing current literature on the topic is also included. Although anecdotal, our experience suggests that peri-operative obinutuzumab administration can block anti-CFH antibodies production safely and effectively, thus ensuring long-lasting protection from post-transplant aHUS relapse, at a reasonable cost. For the first time, we have demonstrated in vivo that obinutuzumab B-cell depleting properties are not significantly affected by eculizumab-induced complement inhibition.https://www.frontiersin.org/articles/10.3389/fimmu.2022.1073808/fullkidney transplantatypical hemolytic uremic syndromeanti-complement factor H antibodyCFHR1/CFHR3 gene mutationDEAP-HUSeculizumab |
| spellingShingle | Evaldo Favi Evaldo Favi Paolo Molinari Carlo Alfieri Carlo Alfieri Giuseppe Castellano Giuseppe Castellano Mariano Ferraresso Mariano Ferraresso Donata Cresseri Case report: Eculizumab plus obinutuzumab induction in a deceased donor kidney transplant recipient with DEAP-HUS Frontiers in Immunology kidney transplant atypical hemolytic uremic syndrome anti-complement factor H antibody CFHR1/CFHR3 gene mutation DEAP-HUS eculizumab |
| title | Case report: Eculizumab plus obinutuzumab induction in a deceased donor kidney transplant recipient with DEAP-HUS |
| title_full | Case report: Eculizumab plus obinutuzumab induction in a deceased donor kidney transplant recipient with DEAP-HUS |
| title_fullStr | Case report: Eculizumab plus obinutuzumab induction in a deceased donor kidney transplant recipient with DEAP-HUS |
| title_full_unstemmed | Case report: Eculizumab plus obinutuzumab induction in a deceased donor kidney transplant recipient with DEAP-HUS |
| title_short | Case report: Eculizumab plus obinutuzumab induction in a deceased donor kidney transplant recipient with DEAP-HUS |
| title_sort | case report eculizumab plus obinutuzumab induction in a deceased donor kidney transplant recipient with deap hus |
| topic | kidney transplant atypical hemolytic uremic syndrome anti-complement factor H antibody CFHR1/CFHR3 gene mutation DEAP-HUS eculizumab |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2022.1073808/full |
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