Microbial IgA protease removes IgA immune complexes from mouse glomeruli in vivo: potential therapy for IgA nephropathy.
The hallmark of IgA nephropathy (IgAN), the most common form of glomerulonephritis, is the presence of mesangial deposits containing IgA, specifically the IgA1 subclass, as the most prominent component. The deposited IgA is considered to be part of an immune complex. The family of enzymes known as bacterial IgA proteases exhibits substrate specificity that is essentially limited to the hinge region of IgA1. Here we demonstrate the ability of systemically administered IgA protease to remove glomerular IgA immune complexes, both the antigen and antibody components, in a passive mouse model of IgAN. Thus, IgA protease may have potential as a therapeutic agent for human IgAN.
Lamm
Michael E
ME
Department of Pathology, Case Western Reserve University, 10900 Euclid Avenue, Wolstein Research Building, Room 5531, Cleveland, OH 44106, USA. mel6@case.edu
Emancipator
Steven N
SN
Robinson
Janet K
JK
Yamashita
Michifumi
M
Fujioka
Hisashi
H
Qiu
Jiazhou
J
Plaut
Andrew G
AG
D000818:Animals; D000936:Antigen-Antibody Complex; D004195:Disease Models, Animal; D005922:Glomerulonephritis, IGA / Q000473:pathology* / Q000628:therapy; D006193:Haemophilus influenzae / Q000378:metabolism; D006801:Humans; D007070:Immunoglobulin A / Q000378:metabolism*; D007668:Kidney / Q000473:pathology / Q000648:ultrastructure; D007678:Kidney Glomerulus / Q000276:immunology* / Q000378:metabolism / Q000648:ultrastructure; D051379:Mice; D008854:Microscopy, Electron; D008856:Microscopy, Fluorescence / Q000379:methods; D015233:Models, Statistical; D017434:Protein Structure, Tertiary; D012697:Serine Endopeptidases / Q000378:metabolism / Q000502:physiology*
D000936:Antigen-Antibody Complex; D007070:Immunoglobulin A; D012697:Serine Endopeptidases; C021433:IgA-specific serine endopeptidase