| Budget Amount *help |
¥3,400,000 (Direct Cost: ¥3,400,000)
Fiscal Year 2001: ¥1,300,000 (Direct Cost: ¥1,300,000)
Fiscal Year 2000: ¥2,100,000 (Direct Cost: ¥2,100,000)
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| Research Abstract |
IgA nephropathy (IgAN) is characterized by the presence of IqA deposits, predominantly in the qlomerular mesangium. Concerning its pathogenesis, several investigators have suggested that the glomerular IgA deposits in IgA N are antibodies (Ab) to viral, bacterial or dietary antigens Thus the Ab are probably produced as part of the specific host immune response to various environmental antigens. We have observed previously that Haemophilus parainfluenzae (HP) is more commonlyisolated from the pharynx of patients with IgAN than from those with other glomerular diseases. We have also identified the glomerular deposition of outer membranes of HP antigens (OMHP) and an increased serum concentration of IgA-Ab against OMHP in patients with IgAN. Furthermore, We have shown that patients with IgAN have a specific increase in the production of IgA-Ab against OMHP via polyclonal activation against these, with switching of production from one isotype to another, e.g. from IgM to IgA, and that a si
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gnificant relationship between IgA-Ab against OMHP and renal lesions exists in patients with IgAN, and that OMHP stimulate tonsillar B-lymphocvtes to produce specific lqA1-Ab against OMHP and tonsillar T-lvmphocytes in patients with IgAN.
Our objective was to investigated the production of IgA and several cytokines by tonsillar lymphocytes (TL) from patients with IgAN induced by stimulation with OMHP. We used TL from the palatine tonsils of patients with IgAN and patients with chronic tonsillitis but without renal diseases as controls. HP was detected in the tonsils of all patients before tonsillectomy. We examined production of IgA-Ab against OMHP and cytokines in the culture supernatants after lymphocyte incubation with OMHP. The spontaneous production of total IgA and TGF-β by TL from patients with IgAN was higher than that by TL from controls. Stimulation with OMHP in vitro enhanced the production of HP-specific IgA by TL from patients with IgAN, but not by TL from controls. OMHP stimulation also enhanced the production of TGF-β and IL-10 by TL from patients with IgAN. Spontaneous IFN-γ production and spontaneous total IgA production by TL were higher in IgAN patients than in controls. IFN-γ induction by OMHP stimulation was also higher in IgAN patients than in controls. IFN-γ production was positively correlated with total IgA values in both IgAN patients and controls. Less
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