The endogenous immune response modulates the course of IgA-immune complex mediated nephropathy.
In animal models of IgA nephropathy, the inevitable endogenous immune response to passively administered antigens alone or in complex with specific IgA mask the exact role each might play in pathogenesis. To delineate the role the immune response might play, we have developed a passive model with exclusive IgA-immune complex-mediated nephropathy in B-cell-deficient (BCD) mice. Glomerular IgA immune deposits were induced by administration of purified IgA antiphosphorylcholine and the specific pneumococcal C-polysaccharide (PnC) antigen daily for 2 weeks into BCD and wild-type (WT) mice. In BCD mice IgA+PnC deposits induced severe glomerular injury and renal dysfunction. In contrast, WT mice developed intense glomerular IgG and IgM and C3 co-deposits of the IgA+PnC with significantly less renal injury. Cytofluorometric analysis revealed that PnC induced in BCD, but not in WT, a rapid and dramatic increase in number of activated CD3(+)/CD69(+) T-cell population. The nuclear factor-kappa B (NF-kappaB) transcription factor was activated early and progressively increased in response to glomerular IgA+PnC deposits. These results suggest that nephritogenic IgA+PnC immune deposits induce glomerular and renal dysfunction through activation of the NF-kappaB. This inflammatory pathway is modulated by the endogenous cellular and antibody response to the antigen affecting the course of IgA nephropathy progression.
Chao
T-K
TK
Graduate Institute of Medical Sciences, National Defense Medical Center, Taipei, Taiwan, Republic of China.
Rifai
A
A
Ka
S-M
SM
Yang
S-M
SM
Shui
H-A
HA
Lin
Y-F
YF
Sytwu
H-K
HK
Lee
W-H
WH
Kung
J T
JT
Chen
A
A
D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology / Q000473:pathology; D018932:Chemokine CCL2 / Q000378:metabolism; D004195:Disease Models, Animal; D005434:Flow Cytometry; D005922:Glomerulonephritis, IGA / Q000276:immunology* / Q000473:pathology*; D007107:Immune System / Q000276:immunology*; D007070:Immunoglobulin A / Q000276:immunology; D015850:Interleukin-6 / Q000097:blood; D007678:Kidney Glomerulus / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D008264:Macrophages / Q000276:immunology / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D009000:Monocytes / Q000276:immunology / Q000473:pathology; D016328:NF-kappa B / Q000378:metabolism; D010767:Phosphorylcholine / Q000276:immunology; D011135:Polysaccharides, Bacterial / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology / Q000473:pathology
C491768:Ccl2 protein, mouse; D018932:Chemokine CCL2; D007070:Immunoglobulin A; D015850:Interleukin-6; D016328:NF-kappa B; D011135:Polysaccharides, Bacterial; C027158:polysaccharide C-substance (Streptococcus); D010767:Phosphorylcholine