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Clinical immunology : the official journal of the Clinical Immunology Society v.183, 2017년, pp.1 - 7   SCI SCIE SCOPUS
본 등재정보는 저널의 등재정보를 참고하여 보여주는 베타서비스로 정확한 논문의 등재여부는 등재기관에 확인하시기 바랍니다.

Alternative complement pathway hemolytic assays reveal incomplete complement blockade in patients treated with eculizumab

Puissant-Lubrano, Bénédicte (Laboratoire d'Immunologie, CHU de Toulouse, Hôpital Rangueil, Toulouse, France ) ; Puissochet, Sylvain (Laboratoire d'Immunogénétique Moléculaire, Université ) ; Congy-Jolivet, Nicolas (Paul Sabatier, Toulouse 3, Toulouse, France ) ; Chauveau, Dominique (Laboratoire d'Immunologie, CHU de Toulouse, Hôpital Rangueil, Toulouse, France ) ; Decramer, Stéphane (Department of Nephrology and Organ Transplantation, CHU Rangueil, Toulouse, France ) ; Garnier, Arnaud (Department of Pediatric Nephrology, CHU Purpan, Toulouse, INSERM 1048, Institute of Cardiovascular and Metabolic Diseases, Toulouse, Université ) ; Huart, Antoine (de Toulouse III Paul Sabatier, Toulouse, France ) ; Kamar, Nassim (Department of Pediatric Nephrology, CHU Purpan, Toulouse, INSERM 1048, Institute of Cardiovascular and Metabolic Diseases, Toulouse, Université ) ; Ribes, David (de Toulouse III Paul Sabatier, Toulouse, France ) ; Blancher, Antoine (Department of Nephrology and Organ Transplantation, CHU Rangueil, Toulouse, France ) ;
  • 초록  

    Abstract Eculizumab is a monoclonal anti-C5 antibody used in the treatment of atypical hemolytic uremic syndrome (aHUS). We monitored complement inhibition in 16 eculizumab-treated patients suffering from HUS or transplant rejection (not aHUS patients). Blood samples were obtained one to four weeks after the last eculizumab injection. We observed that eculizumab efficiently blocked the terminal pathway (TP) through classical pathway (CP) activation measured by kinetic hemolytic assay (HA) ( 23%) or chicken erythrocytes HA (AP100>15%). Conversely, functional ELISA revealed a complete blockade of TP through AP activation in all patients ( Similar results were obtained after in vitro addition of increasing amounts of eculizumab to a control serum ( in vitro APH50>60% and AP100>20%). We also showed that ELISA was less sensitive than HA. Highlights Eculizumab incompletely inhibited terminal pathway through alternative pathway activation. Residual terminal pathway activity is observed in the majority of treated patients. This residual activity is observed only with hemolytic assays. ELISA in less sensitive than hemolytic assay to measure complement activity.


  • 주제어

    Complement classical pathway .   Complement alternative pathway .   Anti-C5 .   Hemolytic assay .   ELISA .   Assay sensitivity .   Drug monitoring.  

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