Case report: Eculizumab plus obinutuzumab induction in a deceased donor kidney transplant recipient with DEAP-HUS

• Published in: Frontiers in immunology Vol. 13; p. 1073808
• Main Authors: Favi, Evaldo, Molinari, Paolo, Alfieri, Carlo, Castellano, Giuseppe, Ferraresso, Mariano, Cresseri, Donata
• Format: Journal Article
• Language: English
• Published: Switzerland Frontiers Media S.A 14.12.2022
• Subjects: anti-complement factor H antibody; atypical hemolytic uremic syndrome; Atypical Hemolytic Uremic Syndrome - genetics; CFHR1/CFHR3 gene mutation; DEAP-HUS; eculizumab; Female; Homozygote; Humans; Immunology; kidney transplant; Kidney Transplantation - adverse effects; Middle Aged; Sequence Deletion; atypical hemolytic uremic syndrome; kidney transplant; case report; eculizumab; CFHR1/CFHR3 gene mutation; DEAP-HUS; obinutuzumab; anti-complement factor H antibody
• ISSN: 1664-3224; 1664-3224
• DOI: 10.3389/fimmu.2022.1073808

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 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 that obinutuzumab B-cell depleting properties are not significantly affected by eculizumab-induced complement inhibition.