Experimental IgA nephropathy. Enhanced deposition of glomerular IgA immune complex in proteinuric states.
BACKGROUND
IgA nephropathy is induced by the IgA-immune complex (IC). IgA nephropathy associated with heavy proteinuria is considered a more progressive form of the disease. To elucidate the mechanism by which the latter condition occurs, we investigated the effect of proteinuria on the glomerular deposition of IgA-IC.


METHODS
BALB/c female mice that had been made proteinuric by adriamycin or bovine serum albumin (BSA) were injected with TEPC-15 hybridoma-derived IgA anti-phosphorylcholine (PC) and individual specific antigens. The 6-hour clearance kinetics of IgA were measured, and the accumulation of IgA deposits and the third complement component (C3) in the glomerulus were analyzed.


RESULTS
The clearance kinetics of 125I-IgA injected together with a specific antigen, PC-conjugated BSA (BSA-PC), showed only a minimal distinction between the experimental (proteinuric) and the control (nonproteinuric) groups of mice. However, analysis of renal tissue by immunofluorescence and light microscopic autoradiography revealed markedly enhanced mesangial IgA-IC deposition in the proteinuric mice receiving IgA and one of three specific antigens, BSA-PC, PC-conjugated cytochrome-c, and a pneumococcal C-polysaccharide. Immunofluorescence also showed augmented mesangial C3 deposition in proteinuric mice that received IgA/PC-conjugated cytochrome-c or IgA/pneumococcal C-polysaccharide. In addition, adriamycin or BSA per se did not influence glomerular IgA-IC localization.


CONCLUSIONS
Glomerular localization of nephritogenic IgA-IC was comparably enhanced in mice with proteinuria induced by various methods. Thus, a vicious cycle for the progression of IgA nephropathy might ensue in proteinuric states.
Chen
A
A
Department of Pathology, Tri-Service General Hospital, Taipei, Taiwan, Republic of China.
Ding
S L
SL
Sheu
L F
LF
Song
Y B
YB
Shieh
S D
SD
Shaio
M F
MF
Chou
W Y
WY
Ho
Y S
YS
D000818:Animals; D000936:Antigen-Antibody Complex / Q000032:analysis / Q000378:metabolism*; D003176:Complement C3 / Q000032:analysis / Q000378:metabolism; D004317:Doxorubicin / Q000633:toxicity; D005260:Female; D005455:Fluorescent Antibody Technique; D005920:Glomerular Mesangium / Q000473:pathology / Q000648:ultrastructure; D005922:Glomerulonephritis, IGA / Q000276:immunology / Q000473:pathology* / Q000652:urine; D006801:Humans; D007070:Immunoglobulin A / Q000032:analysis / Q000378:metabolism*; D007150:Immunohistochemistry; D007668:Kidney / Q000276:immunology / Q000473:pathology*; D008657:Metabolic Clearance Rate; D051379:Mice; D008807:Mice, Inbred BALB C; D016253:Microscopy, Immunoelectron; D010767:Phosphorylcholine / Q000276:immunology; D011507:Proteinuria; D012710:Serum Albumin, Bovine / Q000633:toxicity
D000936:Antigen-Antibody Complex; D003176:Complement C3; D007070:Immunoglobulin A; D010767:Phosphorylcholine; D012710:Serum Albumin, Bovine; D004317:Doxorubicin