Minimal change disease (MCD) is a kidney disease characterized by pathology in the glomeruli. The disease has its name because changes associated with it can only be seen via electron microscopy. The effects on the glomeruli lead to its increase in permeability and subsequent severe loss of proteins in the urine. Immunological changes in the kidney tissue are thought to promote the development of MCD. Research studies have suggested that abnormalities in Foxp3 T regulatory (Treg) cells, which control immune homeostasis, are involved in MCD pathogenesis.
A study of children with MCD showed lower kidney infiltration of Foxp3+ T cells when compared to healthy controls. Another study in children with idiopathic nephrotic syndrome showed an increase in circulating Th17 cells over Treg cells when compared to healthy controls. To better characterize the immune imbalance involved in MCD, researchers determined the balance of Th17, cytotoxic T cells, and Foxp3+ cells in kidney biopsies from MCD patients using immunohistochemistry. Effector T cells in peripheral blood from patients with MCD and healthy controls were also analyzed using flow cytometry. Correlations were made between the immune cell measurements and clinical outcomes.
The kidney cell infiltrate in MCD tissue contained primarily CD4+ (helper) T cells. The density of Th17 and cytotoxic T cells was higher in the MCD tissue when compared to the density of Foxp3+ and Treg cells. Flow cytometry analysis of peripheral blood showed higher percentages of CD3+ and cytotoxic T cells in patients with MCD when compared to healthy controls. However, the number TH17 cells was lower in the blood of patients with MCD when compared to that of healthy controls.
When the immune cell characteristics were compared to the clinical status, it was found that the number of circulating cytotoxic T cells increased with increasing serum creatinine levels and decreasing glomerular filtration rate. The percentage of circulating naïve CD8+ cells increased with increasing proteinuria; however, the ratio of cytotoxic over Foxp3+ T cells increased as glomerular filtration rate decreased. These results suggest that Foxp3+ deficiency and th17 and cytotoxic T cell dominance may be associated with MCD.
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