TY - JOUR
T1 - Halting targeted and collateral damage to red blood cells by the complement system
AU - Jalink, M.
AU - de Boer, E. C. W.
AU - Evers, D.
AU - Havinga, M. Q.
AU - Vos, J. M. I.
AU - Zeerleder, S.
AU - de Haas, M.
AU - Jongerius, I.
N1 - Funding Information: This work is part of the research program Aspasia with project number 015.014.069, which is (partly) financed by the Netherlands Organisation for Scientific Research (NWO) to IJ. In addition, this work was funded by the Product and Process Development grants obtained (in competition) from Sanquin Blood Supply Foundation: PPOD 105 to IJ and PPOC-15-27 to MdH. Publisher Copyright: © 2021, The Author(s).
PY - 2021/12/1
Y1 - 2021/12/1
N2 - 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.
AB - 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.
KW - Autoimmune hemolytic anemia
KW - Complement
KW - Complement inhibitors
KW - Complement therapeutics
KW - Paroxysmal nocturnal hemoglobinuria
UR - http://www.scopus.com/inward/record.url?scp=85120596758&partnerID=8YFLogxK
U2 - https://doi.org/10.1007/s00281-021-00859-8
DO - https://doi.org/10.1007/s00281-021-00859-8
M3 - Review article
C2 - 34191092
SN - 1863-2297
VL - 43
SP - 799
EP - 816
JO - Seminars in immunopathology
JF - Seminars in immunopathology
IS - 6
ER -