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  • Title: Decreased CD4+CD25+ cells and increased dimeric IgA-producing cells in tonsils in IgA nephropathy.
    Author: Huang H, Peng Y, Liu H, Yang X, Liu F.
    Journal: J Nephrol; 2010; 23(2):202-9. PubMed ID: 20213609.
    Abstract:
    BACKGROUND: The relationship between tonsillar autoimmune response and the pathogenesis of IgA nephropathy (IgAN) has been previously demonstrated. However, the role of CD4+CD25+ cells, which play critical roles in maintaining peripheral tolerance and preventing autoimmunity, has not yet been defined in IgAN. METHODS: The lymphocytes from tonsils of all subjects (including 37 IgAN cases and 37 controls without renal diseases) were cultured for 72 hours without stimulation, or with stimulation by alpha-hemolytic streptococcus (HS) isolated from the tonsillar crypts of cases (the HS-IgAN) or controls (HS-controls). The CD4+CD25+ cells were measured by flow cytometry. Expression of J chain mRNA was analyzed by in situ hybridization (ISH) and the dimeric IgA-producing cells were identified by immunofluorescence and fluorescent ISH. RESULTS: The number of CD4+CD25+ cells was significantly lower in cases than in controls (0.98% +/- 0.204% vs. 3.58% +/- 0.554%, 1.37% +/- 0.214% vs. 5.78% +/- 0.562%, and 1.43% +/- 0.202% vs. 6.05% +/- 0.521%, for nonstimulation, HS-controls and HS-cases, respectively). CD4+CD25+ cells from cases showed a significantly lower stimulation index (SI) when stimulated with HS-controls and HS-IgAN than controls (p<0.05), whereas the number of dimeric IgA-producing cells was significantly higher in cases than controls (11.9% +/- 3.1% vs. 6.5% +/- 1.5%, 33.5% +/- 5.7% vs. 13.9% +/- 1.2%, and 35.1% +/- 6.2% vs. 13.9% +/- 1.2%, for nonstimulation, HS-controls and HS-cases, respectively). The dimeric IgA-producing cells from patients with IgAN showed a significantly higher SI when stimulated with HS-controls, or HS-IgAN than those from patients without renal disease (p<0.01). The SI of CD4+CD25+ cells was negatively correlated with that of dimeric IgA-producing cells. CONCLUSION: The results suggest that CD4+CD25+ cells and dimeric IgA-producing cells in tonsils may be related to the pathogenesis of IgAN.
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