Evolution of renal injury in a chronic model of IgA immune-complex-associated nephropathy.
BACKGROUND
IgA nephropathy (IgAN) is characterized by intense and diffuse IgA mesangial deposits, a variety of histopathological changes and unpredictable clinical course. To elucidate the cause of the discrepancy between the unvariable IgA deposition and the histological picture, we examined the short- and long-term influence of glomerular IgA immune complexes (IgA-IC) on the progression of renal lesions in experimental IgAN.


METHODS
IgA-IC renal deposits were induced by sequential administration of IgA antiphosphorylcholine and pneumococcal C polysaccharide. Mice treated every other day by three injections (groups A) or nine injections (groups B) were sacrificed 24 h and 1, 4, or 8 weeks (groups 1-4) after cessation of treatment.


RESULTS
Group A1 showed segmental glomerular necrosis and thrombosis. Lesions then converted to segmental mesangial proliferation (A2), more pronounced in A3 and minimal in A4. Group B1 showed severe proliferative glomerulonephritis and segmental necrosis. The pattern altered to mesangial expansion with glomerular/interstitial infiltration in B2, milder features in B3 and residual mesangial proliferation in B4. Proteinuria increased progressively during treatment reaching its maximum in group B1, but it returned to near normal levels in group B4. The development of proteinuria paralleled glomerular/interstitial T cell infiltration.


CONCLUSIONS
These findings demonstrate that renal histopathological alterations observed in experimental IgA nephropathy are sustainable only by continuous deposition of nephritogenic IgA-IC.
Montinaro
V
V
Institute of Nephrology, University of Bari, Italy.
Aventaggiato
L
L
Cavallo
T
T
Rifai
A
A
D000818:Animals; D000936:Antigen-Antibody Complex / Q000276:immunology*; D002455:Cell Division; D002908:Chronic Disease; D004195:Disease Models, Animal; D005455:Fluorescent Antibody Technique; D005922:Glomerulonephritis, IGA / Q000276:immunology / Q000378:metabolism / Q000473:pathology*; D007070:Immunoglobulin A / Q000276:immunology*; D051379:Mice; D011507:Proteinuria / Q000378:metabolism / Q000473:pathology
D000936:Antigen-Antibody Complex; D007070:Immunoglobulin A