Complement catalyzing glomerular diseases

TY - JOUR

T1 - Complement catalyzing glomerular diseases

AU - Zipfel, Peter F

AU - Wiech, Thorsten

AU - Gröne, Hermann-Josef

AU - Skerka, Christine

N1 - © 2021. The Author(s).

PY - 2021/8

Y1 - 2021/8

N2 - Complement is an evolutionarily conserved system which is important in the defense against microorganisms and also in the elimination of modified or necrotic elements of the body. Complement is activated in a cascade type manner and activation and all steps of cascade progression are tightly controlled and regulatory interleaved with many processes of inflammatory machinery. Overshooting of the complement system due to dysregulation can result in the two prototypes of primary complement mediated renal diseases: C3 glomerulopathy and thrombotic microangiopathy. Apart from these, complement also is highly activated in many other inflammatory native kidney diseases, such as membranous nephropathy, ANCA-associated necrotizing glomerulonephritis, and IgA nephropathy. Moreover, it likely plays an important role also in the transplant setting, such as in antibody-mediated rejection or in hematopoietic stem cell transplant associated thrombotic microangiopathy. In this review, these glomerular disorders are discussed with regard to the role of complement in their pathogenesis. The consequential, respective clinical trials for complement inhibitory therapy strategies for these diseases are described.

AB - Complement is an evolutionarily conserved system which is important in the defense against microorganisms and also in the elimination of modified or necrotic elements of the body. Complement is activated in a cascade type manner and activation and all steps of cascade progression are tightly controlled and regulatory interleaved with many processes of inflammatory machinery. Overshooting of the complement system due to dysregulation can result in the two prototypes of primary complement mediated renal diseases: C3 glomerulopathy and thrombotic microangiopathy. Apart from these, complement also is highly activated in many other inflammatory native kidney diseases, such as membranous nephropathy, ANCA-associated necrotizing glomerulonephritis, and IgA nephropathy. Moreover, it likely plays an important role also in the transplant setting, such as in antibody-mediated rejection or in hematopoietic stem cell transplant associated thrombotic microangiopathy. In this review, these glomerular disorders are discussed with regard to the role of complement in their pathogenesis. The consequential, respective clinical trials for complement inhibitory therapy strategies for these diseases are described.

KW - Animals

KW - Humans

KW - Kidney/pathology

KW - Kidney Glomerulus/pathology

U2 - 10.1007/s00441-021-03485-w

DO - 10.1007/s00441-021-03485-w

M3 - SCORING: Review article

C2 - 34613485

VL - 385

SP - 355

EP - 370

JO - CELL TISSUE RES

JF - CELL TISSUE RES

SN - 0302-766X

IS - 2

ER -