Treatment of Anti-HLA Donor-Specific Antibodies Results in Increased Infectious Complications and Impairs Survival after Liver Transplantation.

Sinem Ünlü,Frank Tacke,Wenzel Schöning,Moritz Schmelzle,Matthias Biebl,Tomasz Dziodzio,Petra Reinke,Paul Viktor Ritschl,Christian Denecke,Dennis Eurich,Safak Gül-Klein,Nils Lachmann,Maximilian Jara,Johann Pratschke,Robert Öllinger,Leke Wiering,Sascha Chopra

doi:10.3390/jcm9123986

Abstract

Donor-specific anti-human leukocyte antigen antibodies (DSA) are controversially discussed in the context of liver transplantation (LT). We investigated the relationship between the presence of DSA and the outcome after LT. All the LTs performed at our center between 1 January 2008 and 31 December 2015 were examined. Recipients < 18 years, living donor-, combined, high-urgency-, and re-transplantations were excluded. Out of 510 LTs, 113 DSA-positive cases were propensity score-matched with DSA-negative cases based on the components of the Balance of Risk score. One-, three-, and five-year survival after LT were 74.3% in DSA-positive vs. 84.8% (p = 0.053) in DSA-negative recipients, 71.8% vs. 71.5% (p = 0.821), and 69.3% vs. 64.9% (p = 0.818), respectively. Rejection therapy was more often applied to DSA-positive recipients (n = 77 (68.1%) vs. 37 (32.7%) in the control group, p < 0.001). At one year after LT, 9.7% of DSA-positive patients died due to sepsis compared to 1.8% in the DSA-negative group (p = 0.046). The remaining causes of death were comparable in both groups (cardiovascular 6.2% vs. 8.0%; p = 0.692; hepatic 3.5% vs. 2.7%, p = 0.788; malignancy 3.5% vs. 2.7%, p = 0.788). DSA seem to have an indirect effect on the outcome of adult LTs, impacting decision-making in post-transplant immunosuppression and rejection therapies and ultimately increasing mortality due to infectious complications.

Highlights

The clinical relevance of donor-specific anti-human leukocyte antigen antibodies (DSA) in liver transplantation (LT) has been the basis for many controversial discussions
Class II DSA were present in 50.9% (n = 28) of the patients with de novo and 10.2% of those with preformed DSA (n = 5, p < 0.001)
This study demonstrates that especially preformed DSA are associated with an impaired patient survival after LT, and sepsis-related mortality needs to be considered as a major cause

Summary

Introduction

The clinical relevance of donor-specific anti-human leukocyte antigen antibodies (DSA) in liver transplantation (LT) has been the basis for many controversial discussions. Med. 2020, 9, 3986 the negative effects of preformed and de novo DSA on patient and graft survival have been well demonstrated [1,2]. The presence of DSA in other solid organ transplantations, such as othf ethneegluantigve[3e]ff, ehcetsarotf[p4]r,efoorrmpaendcraenads d[5e],nhoavso bDeSeAn roenpopratteidenttoabned agsrsaofctisauterdvivwailthhaivnefebrieoerngwraefltl oduetmcoomnsetsr.aFteodr m[1a,2n]y. Fyueratrhse, rlimveorreg,rtahfetsphraevseenbceeeonfcDonSAsidineroetdhleersssovliudlnoerrgaabnletrtaonDspSlAandtauteiotnost,hseugchraafts soizf et,hdeulaulnbglo[o3d],shuepaprlty,[4a]n,dotrhpeapnactrieenats’s[5o]w, nhaims bmeuennorleopgoicratleadcttiovibtye [a6s]s. OSciniacteetdhewfiitrhst ionbfseerriovratgiornafst oofuatcnotimboeds.yF-moremdiaanteydyreeajersc,tiloivnesr(gArBafMtsRh)aivneLbTee3n0 cyoenasrisdaegreod[7le],ssesvpuelcniearlalyblreectoenDtSdAatdauheatvoetlheedgtroaaft nseizwe, pdeuraclebpltoioond soufpDpSlyA, ainndtthhee cpoantiteenxtt’soof wLTn.imInm2u0n1o6,lotghiecaBl aanctfifvWityo[r6k]i.nSginGcerotuhpe fiprrsotvoibdseedrvaatfiiornsts aopfparnotaibchodoyn-smtaenddiaatreddizreedje(chtiisotnospa(AthBoMloRgi)cianl)LATB3M0Rycerairtseraiago[8[]7a]n, desnpeewcialallbyorreactoernyt tdeacthanhiqauvees,lesductho aasntehwe Lpuermceinpetxio®naossfaDy,SAheilnpitnhge tcoonatcehxitevoef LaTm. Ionre20p1r6e,ctihsee aBnatnibffoWdyordkeintegctGiorno,uspppecriofviciadteiodna, afinrdst qaupapnrtoiaficchatioonn s[t9a,1n0d]a. Ionre20p1r6e,ctihsee aBnatnibffoWdyordkeintegctGiorno,uspppecriofviciadteiodna, afinrdst qaupapnrtoiaficchatioonn s[t9a,1n0d]a. rAddizdeidtio(nhaislltyo,ppaaththoolologgicicalc)oAndBiMtioRnscrsiutecrhiaas[8T]-caenldl-mneedwialtaebdorreajteocrtyiontesc(hTnCiqMuRes), asnudchinafsectthioenLsucmaninleeaxd®toasasnayu, phreelgpuinlagtitoonaocfhtiiesvsueeahmumoraenplereuckiosecyatnetaibnotidgyend(eHteLcAtio) nex, pspreescsiifiocnatainodn, manadkequthaentliifivceartgiornaf[t9m,10o]r.eAsudsdcietipotniballley,topaAthBoMloRgi[c6c,1o1n,d12it]i.ons such as T-cell-mediated rejections (TCMR) and Rinefceecntitonfisncdainnglesaidndtoicaanteuapnreagsusloactiiaotnioonf tbisestuweeehnumDaSnAleaunkdoceyatrelya/ncthirgoennic(HrLejAec)teioxnpsreasnsidongraanfdt imnjaukrye t[h1e3–l1iv8e]rHgorawftevmeor,rethseudscaetpatribegleartodiAngBMthRe i[m6,1p1a,c1t2o].f DSA on patient and graft survival after LT are leRsseccelenatr fi[1n3d–i1n6g,1s8i–n2d3i]c.ate an association between DSA and early/chronic rejections and graft injurCyo[n13se–q1u8]enHtolyw, etvheerr,ethise dstaitlal raegnaereddinfgorthdeaitma ptaoctcloafrDifySAthoenepfafetcietsntoafnDd SgAra’fst psurervseivnacleaoftnerLLTT oauretcloemssecsl.eTarhe[1a3i–m16o,1f8t–h2i3s]s.tudy was to investigate the impact of DSA on patient and graft survival by meCaonnssoeqf uaemntaltyc,hthederecaisses-tciollnatrnoeleadnfaolyr sdisataantdo tcolairdifeyntthifeyerffisekctfsacotfoDrsSfAo’rs ipnrfeesreionrcepaotnieLnTt oanudtcogmraefts

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