C1-inhibitor treatment in patients with severe complement-mediated autoimmune hemolytic anemia.

Autor:	de Boer ECW; Department of Immunopathology, Sanquin Research and Landsteiner Laboratory, Amsterdam University Medical Centre, Amsterdam Infection and Immunity Institute, Amsterdam, The Netherlands.; Department of Pediatric Immunology, Rheumatology, and Infectious Diseases, Emma Children's Hospital, Amsterdam University Medical Center, Amsterdam, The Netherlands., Jalink M; Department of Clinical Transfusion Research, Sanquin Research, Amsterdam, The Netherlands.; Department of Hematology, Amsterdam University Medical Center, Amsterdam, The Netherlands.; Department of Transfusion Medicine, Sanquin Blood Supply, Amsterdam, The Netherlands., Delvasto-Nuñez L; Department of Immunopathology, Sanquin Research and Landsteiner Laboratory, Amsterdam University Medical Centre, Amsterdam Infection and Immunity Institute, Amsterdam, The Netherlands., Meulenbroek EM; Department of Immunopathology, Sanquin Research and Landsteiner Laboratory, Amsterdam University Medical Centre, Amsterdam Infection and Immunity Institute, Amsterdam, The Netherlands., Baas I; Department of Immunopathology, Sanquin Research and Landsteiner Laboratory, Amsterdam University Medical Centre, Amsterdam Infection and Immunity Institute, Amsterdam, The Netherlands., Janssen SR; Department of Hematology, Amsterdam University Medical Center, Amsterdam, The Netherlands., Folman CC; Department of Immunohematology Diagnostics, Sanquin, Amsterdam, The Netherlands., Gelderman KA; Sanquin Diagnostic Services, Amsterdam, The Netherlands., Wouters D; Centre for Infectious Disease Control, National Institute for Public Health and the Environment, Bilthoven, The Netherlands., Engel MD; Department of Hematology, Amsterdam University Medical Center, Amsterdam, The Netherlands., de Haas M; Department of Clinical Transfusion Research, Sanquin Research, Amsterdam, The Netherlands.; Department of Immunohematology Diagnostics, Sanquin, Amsterdam, The Netherlands.; Department of Hematology, Leiden University Medical Center, Leiden, The Netherlands., Kersten MJ; Department of Hematology, Amsterdam University Medical Centers, Location University of Amsterdam, Cancer Center Amsterdam and Lymphoma and Myeloma Center Amsterdam, Amsterdam, The Netherlands., Jongerius I; Department of Immunopathology, Sanquin Research and Landsteiner Laboratory, Amsterdam University Medical Centre, Amsterdam Infection and Immunity Institute, Amsterdam, The Netherlands.; Department of Pediatric Immunology, Rheumatology, and Infectious Diseases, Emma Children's Hospital, Amsterdam University Medical Center, Amsterdam, The Netherlands., Zeerleder S; Department of Hematology, Luzerner Kantonsspital, Luzern, Switzerland.; Department for BioMedical Research, University of Bern, Bern, Switzerland., Vos JMI; Department of Immunohematology Diagnostics, Sanquin, Amsterdam, The Netherlands.; Department of Hematology, Amsterdam University Medical Centers, Location University of Amsterdam, Cancer Center Amsterdam and Lymphoma and Myeloma Center Amsterdam, Amsterdam, The Netherlands.
Jazyk:	angličtina
Zdroj:	Blood advances [Blood Adv] 2023 Jul 11; Vol. 7 (13), pp. 3128-3139.
DOI:	10.1182/bloodadvances.2022009402
Abstrakt:	Complement-mediated (CM) autoimmune hemolytic anemia (AIHA) is characterized by the destruction of red blood cells (RBCs) by autoantibodies that activate the classical complement pathway. These antibodies also reduce transfusion efficacy via the lysis of donor RBCs. Because C1-inhibitor (C1-INH) is an endogenous regulator of the classical complement pathway, we hypothesized that peritransfusional C1-INH in patients with severe CM-AIHA reduces complement activation and hemolysis, and thus enhances RBC transfusion efficacy. We conducted a prospective, single-center, phase 2, open-label trial (EudraCT2012-003710-13). Patients with confirmed CM-AIHA and indication for the transfusion of 2 RBC units were eligible for inclusion. Four IV C1-INH doses (6000, 3000, 2000, and 1000 U) were administered with 12-hour intervals around RBC transfusion. Serial blood samples were analyzed for hemolytic activity, RBC opsonization, complement activation, and inflammation markers. Ten patients were included in the study. C1-INH administration increased plasma C1-INH antigen and activity, peaking at 48 hours after the first dose and accompanied by a significant reduction of RBC C3d deposition. Hemoglobin levels increased briefly after transfusion but returned to baseline within 48 hours. Overall, markers of hemolysis, inflammation, and complement activation remained unchanged. Five grade 3 and 1 grade 4 adverse event occurred but were considered unrelated to the study medication. In conclusion, peritransfusional C1-INH temporarily reduced complement activation. However, C1-INH failed to halt hemolytic activity in severe transfusion-dependent-CM-AIHA. We cannot exclude that posttransfusional hemolytic activity would have been even higher without C1-INH. The potential of complement inhibition on transfusion efficacy in severe CM-AIHA remains to be determined. (© 2023 by The American Society of Hematology. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved.)
Databáze:	MEDLINE
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