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The contribution of the alternative pathway in complement activation on cell surfaces depends on the strength of classical pathway initiation.
de Boer, Esther Cw; Thielen, Astrid Jf; Langereis, Jeroen D; Kamp, Angela; Brouwer, Mieke C; Oskam, Nienke; Jongsma, Marlieke L; Baral, April J; Spaapen, Robbert M; Zeerleder, Sacha; Vidarsson, Gestur; Rispens, Theo; Wouters, Diana; Pouw, Richard B; Jongerius, Ilse.
Afiliação
  • de Boer EC; Department of Immunopathology, Sanquin Research and Landsteiner Laboratory Amsterdam Infection and Immunity Institute, Amsterdam University Medical Centre Amsterdam The Netherlands.
  • Thielen AJ; Department of Pediatric Immunology, Rheumatology, and Infectious Diseases, Emma Children's Hospital Amsterdam University Medical Centre Amsterdam The Netherlands.
  • Langereis JD; Department of Immunopathology, Sanquin Research and Landsteiner Laboratory Amsterdam Infection and Immunity Institute, Amsterdam University Medical Centre Amsterdam The Netherlands.
  • Kamp A; Laboratory of Medical Immunology, Radboud Institute for Molecular Life Sciences Radboudumc Nijmegen The Netherlands.
  • Brouwer MC; Radboud Center for Infectious Diseases, Radboudumc Nijmegen The Netherlands.
  • Oskam N; Department of Immunopathology, Sanquin Research and Landsteiner Laboratory Amsterdam Infection and Immunity Institute, Amsterdam University Medical Centre Amsterdam The Netherlands.
  • Jongsma ML; Department of Immunopathology, Sanquin Research and Landsteiner Laboratory Amsterdam Infection and Immunity Institute, Amsterdam University Medical Centre Amsterdam The Netherlands.
  • Baral AJ; Department of Immunopathology, Sanquin Research and Landsteiner Laboratory Amsterdam Infection and Immunity Institute, Amsterdam University Medical Centre Amsterdam The Netherlands.
  • Spaapen RM; Department of Immunopathology, Sanquin Research and Landsteiner Laboratory Amsterdam Infection and Immunity Institute, Amsterdam University Medical Centre Amsterdam The Netherlands.
  • Zeerleder S; Translational and Clinical Research Institute Newcastle upon Tyne UK.
  • Vidarsson G; Department of Immunopathology, Sanquin Research and Landsteiner Laboratory Amsterdam Infection and Immunity Institute, Amsterdam University Medical Centre Amsterdam The Netherlands.
  • Rispens T; Department of Immunopathology, Sanquin Research and Landsteiner Laboratory Amsterdam Infection and Immunity Institute, Amsterdam University Medical Centre Amsterdam The Netherlands.
  • Wouters D; Department of Hematology, Luzerner Kantonsspital Luzern and University of Bern Bern Switzerland.
  • Pouw RB; Department for BioMedical Research University of Bern Bern Switzerland.
  • Jongerius I; Department of Experimental Immunohematology, Sanquin Research, and Landsteiner Laboratory Amsterdam University Medical Center Amsterdam The Netherlands.
Clin Transl Immunology ; 12(1): e1436, 2023.
Article em En | MEDLINE | ID: mdl-36721662
Objectives: The complement system is an important component of innate immunity. The alternative pathway (AP) amplification loop is considered an essential feed forward mechanism for complement activation. However, the role of the AP in classical pathway (CP) activation has only been studied in ELISA settings. Here, we investigated its contribution on physiologically relevant surfaces of human cells and bacterial pathogens and in antibody-mediated complement activation, including in autoimmune haemolytic anaemia (AIHA) setting with autoantibodies against red blood cells (RBCs). Methods: We evaluated the contribution of the AP to complement responses initiated through the CP on human RBCs by serum of AIHA patients and recombinant antibodies. Moreover, we studied complement activation on Neisseria meningitidis and Escherichia coli. The effect of the AP was examined using either AP-depleted sera or antibodies against factor B and factor D. Results: We show that the amplification loop is redundant when efficient CP activation takes place. This is independent of the presence of membrane-bound complement regulators. The role of the AP may become significant when insufficient CP complement activation occurs, but this depends on antibody levels and (sub)class. Our data indicate that therapeutic intervention in the amplification loop will most likely not be effective to treat antibody-mediated diseases. Conclusion: The AP can be bypassed through efficient CP activation. The AP amplification loop has a role in complement activation during conditions of modest activation via the CP, when it can allow for efficient complement-mediated killing.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Idioma: En Ano de publicação: 2023 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Idioma: En Ano de publicação: 2023 Tipo de documento: Article