Morphological features in IgA nephropathy.
The hallmark of Berger's disease is the mesangial and/or mesangioparietal deposition of IgA as the predominant or sole immunoglobulin. Despite similar appearance to the immunohistological pattern, morphological glomerular lesions differ in that they are wide ranging and variable, making precise and uniform classificatory approaches extremely difficult. The most characteristic and frequent abnormality is mesangial enlargement, which is produced by various combinations of excess of matrix and of hypercellularity, ranging from minimal to very extensive. In some cases the mesangial lesions are more severe giving a pattern of membrano-proliferative glomerulonephritis. The concomitant presence of necrotizing alterations of glomerular tuft with segmental extracapillary proliferation, similar to capillaritis of Henoch-Schönlein purpura and ANCA associated vasculitis, is now well documented and recognized by researchers. This similarity with vasculitic lesions is confirmed by the strong positivity of fibrinogen, of VCAM-1, and of the accumulation of monocytes within the same areas of segmental necrotic glomerular lesions. These active lesions appear to play a crucial role in the progression of the disease due to repeat formations of necrotizing/extracapillary alterations with subsequent glomerular sclerosis and fibrous adhesions. In the last decade, many groups of investigators have focused their attention on tubulo-interstitial lesions in IgA nephropathy, in particular, on leukocyte infiltration and intersitial fibrosis, demonstrating that the impairment of the glomerular filtration rate and the progression of the disease correlate better with tubulo-interstitial damage than with the degree of glomerular damage. This has also been confirmed by studies with repeat biopsies. Moreover, the recent availability of immunohistochemical and in situ hybridation methods that allow more precise evaluations of infiltrating cells and of numerous factors secreted by these cells (chemokines, cytokines, adhesion molecules etc ...) offers us incredible opportunities to expand our knowledge on mechanisms involved in the inflammatory process and in the progression of the disease.
Renal Immunopathology Center, S. Carlo Borromeo Hospital, Milano, Italy.
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Ferrario
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Rastaldi
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Napodano
D001706:Biopsy; D018450:Disease Progression; D005340:Fibrinogen / Q000032:analysis; D005355:Fibrosis; D005922:Glomerulonephritis, IGA / Q000145:classification / Q000276:immunology / Q000473:pathology*; D006801:Humans; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D007249:Inflammation; D008854:Microscopy, Electron; D009000:Monocytes / Q000473:pathology; D009336:Necrosis; D012720:Severity of Illness Index; D019010:Vascular Cell Adhesion Molecule-1 / Q000032:analysis
D019010:Vascular Cell Adhesion Molecule-1; D005340:Fibrinogen