Halting targeted and collateral damage to red blood cells by the complement system
Seminars in Immunopathology, vol. 43, pp. 799–816
Abstract
The complement system is an important defense mechanism against pathogens; however, in certain pathologies, the system also attacks human cells, such as red blood cells (RBCs). In paroxysmal nocturnal hemoglobinuria (PNH), RBCs lack certain complement regulators which sensitize them to complement-mediated lysis, while in autoimmune hemolytic anemia (AIHA), antibodies against RBCs may initiate complement-mediated hemolysis. In recent years, complement inhibition has improved treatment prospects for these patients, with eculizumab now the standard of care for PNH patients. Current complement inhibitors are however not sufficient for all patients, and they come with high costs, patient burden, and increased infection risk. This review gives an overview of the underlying pathophysiology of complement-mediated hemolysis in PNH and AIHA, the role of therapeutic complement inhibition nowadays, and the high number of complement inhibitors currently under investigation, as for almost every complement protein, an inhibitor is being developed. The focus lies with novel therapeutics that inhibit complement activity specifically in the pathway that causes pathology or those that reduce costs or patient burden through novel administration routes.
Authors 8
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Sanquin · Amsterdam University Medical Centers · University of Amsterdam
Affiliation as printed
Department of Hematology, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands
Sanquin Research, Center for Clinical Transfusion Research, Plesmanlaan 125, 1066, CX, Amsterdam, The Netherlands
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Sanquin · Emma Kinderziekenhuis · Amsterdam University Medical Centers · Amsterdam institute for Immunology and Infectious Diseases
Affiliation as printed
Department of Pediatric Immunology, Rheumatology, and Infectious Diseases, Emma Children's Hospital, Amsterdam University Medical Centre, Amsterdam, The Netherlands
Sanquin Research, Department of Immunopathology, and Landsteiner Laboratory, Amsterdam University Medical Centre, Amsterdam Infection and Immunity Institute, Amsterdam, The Netherlands
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Radboud University Medical Center
Affiliation as printed
Department of Hematology, Radboud University Medical Center, Nijmegen, The Netherlands
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Sanquin · Amsterdam University Medical Centers · Amsterdam institute for Immunology and Infectious Diseases
Affiliation as printed
Sanquin Research, Department of Immunopathology, and Landsteiner Laboratory, Amsterdam University Medical Centre, Amsterdam Infection and Immunity Institute, Amsterdam, The Netherlands
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Sanquin · Amsterdam University Medical Centers · University of Amsterdam
Affiliation as printed
Department of Hematology, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands
Department of Immunohematology Diagnostics, Sanquin, Amsterdam, The Netherlands
Lymphoma and Myeloma Center Amsterdam (LYMMCARE), Amsterdam, The Netherlands
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University of Bern · University Hospital of Bern · Sanquin · Amsterdam University Medical Centers · Amsterdam institute for Immunology and Infectious Diseases
Affiliation as printed
Department for BioMedical Research, University of Bern, Bern, Switzerland
Department of Hematology and Central Hematology Laboratory, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland
Sanquin Research, Department of Immunopathology, and Landsteiner Laboratory, Amsterdam University Medical Centre, Amsterdam Infection and Immunity Institute, Amsterdam, The Netherlands
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Leiden University Medical Center · Sanquin
Affiliation as printed
Department of Hematology, Leiden University Medical Center, Leiden, The Netherlands
Department of Immunohematology Diagnostics, Sanquin, Amsterdam, The Netherlands
Sanquin Research, Center for Clinical Transfusion Research, Plesmanlaan 125, 1066, CX, Amsterdam, The Netherlands
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Ilse Jongerius corresponding
Sanquin · Emma Kinderziekenhuis · Amsterdam University Medical Centers · Amsterdam institute for Immunology and Infectious Diseases
Affiliation as printed
Department of Pediatric Immunology, Rheumatology, and Infectious Diseases, Emma Children's Hospital, Amsterdam University Medical Centre, Amsterdam, The Netherlands. i.jongerius@sanquin.nl
Sanquin Research, Department of Immunopathology, and Landsteiner Laboratory, Amsterdam University Medical Centre, Amsterdam Infection and Immunity Institute, Amsterdam, The Netherlands. i.jongerius@sanquin.nl
Sanquin Research, Department of Immunopathology, and Landsteiner Laboratory, Amsterdam University Medical Centre, Amsterdam Infection and Immunity Institute, Amsterdam, The Netherlands
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