Sequential Targeting of CD52 and TNF Allows Early Minimization Therapy in Kidney Transplantation: From a Biomarker to Targeting in a Proof-Of-Concept Trial.
PLoS One, 2017;12(1):e0169624.
Viklicky O[1, 2], Hruba P[2], Tomiuk S[3], Schmitz S[3], Gerstmayer B[3], Sawitzki B[4, 5], Miqueu P[6, 7], Mrazova P[2], Tycova I[2], Svobodova E[8], Honsova E[9], Janssen U[3], Volk HD[4, 5], Reinke P[5, 10]
Affiliations
PMID: 28085915DOI: 10.1371/journal.pone.0169624
Impact factor: 3.752
Abstract
background: There is high medical need for safe long-term immunosuppression monotherapy in kidney transplantation. Selective targeting of post-transplant alloantigen-(re)activated effector-T cells by anti-TNF antibodies after global T cell depletion may allow safe drug minimization, however, it is unsolved what might be the best maintenance monotherapy.
methods: In this open, prospective observational single-centre trial, 20 primary deceased donor kidney transplant recipients received 2x20 mg Alemtuzumab (d0/d1) followed by 5 mg/kg Infliximab (d2). For 14 days all patients received only tacrolimus, then they were allocated to either receive tacrolimus (TAC, n = 13) or sirolimus (SIR, n = 7) monotherapy, respectively. Protocol biopsies and extensive immune monitoring were performed and patients were followed-up for 60 months.
results: TAC-monotherapy resulted in excellent graft survival (5yr 92%, 95%CI: 56.6-98.9) and function, normal histology, and no proteinuria. Immune monitoring revealed low intragraft inflammation (urinary IP-10) and hints for the development of operational tolerance signature in the TAC- but not SIR-group. Remarkably, the TAC-monotherapy was successful in all five presensitized (ELISPOT+) patients. However, recruitment into SIR-arm was stopped (after n = 7) because of high incidence of proteinuria and acute/chronic rejection in biopsies. No opportunistic infections occurred during follow-up.
conclusions: In conclusion, our novel fast-track TAC-monotherapy protocol is likely to be safe and preliminary results indicated an excellent 5-year outcome, however, a full-scale study will be needed to confirm our findings.
trial registration: EudraCT Number: 2006-003110-18.
MeSH terms
Adult; Antigens, CD; Antigens, Neoplasm; Biomarkers; CD52 Antigen; Female; Gene Expression Profiling; Glycoproteins; Graft Rejection; Humans; Immunosuppressive Agents; Kidney Transplantation; Male; Middle Aged; Monitoring, Immunologic; Prospective Studies; Sirolimus; Tacrolimus; Tumor Necrosis Factor-alpha; Young Adult
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