C Legendre1,2,3, R Sberro-Soussan1, J Zuber1,2,4, V Frémeaux-Bacchi5,6. 1. Service de Néphrologie-Transplantation, Hôpital Necker, Assistance Publique-Hôpitaux de Paris, Paris, France. 2. Université Sorbonne Paris Cité, Paris, France. 3. Inserm U1151, INEM, Hôpital necker, Paris, France. 4. Inserm UMRS 1163, Imagine Institute, Hôpital Necker, Paris, France. 5. Laboratoire d'Immunologie Biologique, Hôpital Européen Georges Pompidou, Assistance Publique-Hôpitaux de paris, Paris, France. 6. INSERM UMRS-1138, Cordeliers Research Center, Complement and Diseases Team, Paris, France.
Abstract
INTRODUCTION AND BACKGROUND: The complement system which belongs to the innate immune system acts both as a first line of defence against various pathogens and as a guardian of host homeostasis. The role of complement has been recently highlighted in several aspects of kidney transplantation: ischaemia-reperfusion, antibody-mediated rejection and native kidney disease recurrence. SOURCES OF DATA: Experimental data, availability of complement-blocking molecules (mainly the anti-C5 monoclonal antibody, eculizumab) and several trials in human kidney transplant recipients has led to some areas of agreement and some disappointment. AREAS OF AGREEMENT AND CONTROVERSIES: So far, eculizumab has shown great efficacy in treatment and prevention of atypical haemolytic and uraemic syndrome, some efficacy in the prevention of antibody-mediated and so far no efficacy in the prevention of delayed graft function. GROWING POINTS: Among the numerous potentially available drugs potentially interfering with complement, recent focus has been made on C1 blockers in the setting of antibody-mediated rejection with promising results. AREAS TIMELY FOR DEVELOPING RESEARCH: Complement is now recognized as a major player in transplant immunology, several targets are going to be tested to define precisely which ones may be potentially useful in clinical practice.
INTRODUCTION AND BACKGROUND: The complement system which belongs to the innate immune system acts both as a first line of defence against various pathogens and as a guardian of host homeostasis. The role of complement has been recently highlighted in several aspects of kidney transplantation: ischaemia-reperfusion, antibody-mediated rejection and native kidney disease recurrence. SOURCES OF DATA: Experimental data, availability of complement-blocking molecules (mainly the anti-C5 monoclonal antibody, eculizumab) and several trials in human kidney transplant recipients has led to some areas of agreement and some disappointment. AREAS OF AGREEMENT AND CONTROVERSIES: So far, eculizumab has shown great efficacy in treatment and prevention of atypical haemolytic and uraemic syndrome, some efficacy in the prevention of antibody-mediated and so far no efficacy in the prevention of delayed graft function. GROWING POINTS: Among the numerous potentially available drugs potentially interfering with complement, recent focus has been made on C1 blockers in the setting of antibody-mediated rejection with promising results. AREAS TIMELY FOR DEVELOPING RESEARCH: Complement is now recognized as a major player in transplant immunology, several targets are going to be tested to define precisely which ones may be potentially useful in clinical practice.
Authors: Giuseppe Castellano; Rossana Franzin; Fabio Sallustio; Alessandra Stasi; Barbara Banelli; Massimo Romani; Giuseppe De Palma; Giuseppe Lucarelli; Chiara Divella; Michele Battaglia; Antonio Crovace; Francesco Staffieri; Giuseppe Grandaliano; Giovanni Stallone; Pasquale Ditonno; Paolo Cravedi; Vincenzo Cantaluppi; Loreto Gesualdo Journal: Aging (Albany NY) Date: 2019-07-08 Impact factor: 5.682