Immunopathological aspects of immunoglobulin A nephropathy and other mesangial proliferative glomerulonephritides.
Immunoglobulin A nephropathy (IgAN) is an immune complex (IC) glomerulonephritis (GN) that represents one of the most common forms of primary glomerular disease. Proliferation of mesangial cells and the increase of mesangial matrix are histological hallmarks of mesangioproliferative GN. Increased serum levels of IgA, polymeric IgA, IgA rheumatoid factor, IgA-IC, and spontaneous or pokeweed mitogen-induced production of IgA by peripheral blood mononuclear cells are major humoral immune alterations reported in IgAN. Recently, we focused on the role of cytokines and growth factors in the mediation of glomerular injury. Platelet-derived growth factor, transforming growth factor beta, interleukin (IL)-1 and IL-6 are expressed by and act on mesangial cells. Increased expression of platelet-derived growth factor was found in both an active model of IgAN and in renal biopsies of patients with proliferative GN. A strict correlation between increased expression of B-chain mRNA and mesangial proliferation was found. Cytokines such as IL-1, interferon gamma, and IL-6, released by infiltrating mononuclear cells or produced locally by mesangial cells, affect the glomerular response to IgA-IC. In a passive murine experimental model of IgAN, IL-1 and interferon gamma increased mesangial hypercellularity, whereas IL-6 was highly pathogenic when associated to IL-1. In conclusion, classical immunological mechanisms in mesangial GN could interact with other pathways involving cytokines and growth factors in the progression of glomerular injury.
Schena
F P
FP
Division of Nephrology, University of Bari, Italy.
Gesualdo
L
L
Montinaro
V
V
D000818:Animals; D016207:Cytokines / Q000502:physiology; D005922:Glomerulonephritis, IGA / Q000209:etiology / Q000276:immunology* / Q000473:pathology; D015432:Glomerulonephritis, Membranoproliferative / Q000209:etiology / Q000276:immunology* / Q000473:pathology; D006133:Growth Substances / Q000502:physiology; D006801:Humans
D016207:Cytokines; D006133:Growth Substances