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Article Type

Original Study

Abstract

Introduction Chronic inflammation and immune inadequacy are present in chronic kidney disease (CKD) patients. T-helper type 17 (Th17) cells give rise to interleukin (IL)-17, IL-22, and IL-23, cause neutrophils to drive to sites of infection, and enhance moderate immune reactions to microbes outside the cells. They are responsible for autoimmune diseases. Regulatory T (Treg) cells secrete anti-inflammatory cytokines IL-10 and transforming growth factor beta and suppress immune reactions to preserve immune homeostasis. The decreased count or disability of Treg leads to immune dysregulation. Endoplasmic reticulum stress (ERS) leads to unfolded protein response that is stimulated by glucose-regulated protein 78 (GRP78). Permanent ERS enhances the transcription of CCAAT-enhancer-binding protein homologous protein (CEBPD or CHOP), which is a proapoptotic gene. The aim of our study was to assess the relationship between immune dysregulation and ERS in CKD for better outcome. Patients and methods In all, 68 CKD patients and 20 apparently healthy participants, selected according to estimated glomerular filtration rate, were recruited to our study from the National Institute of Urology and Nephrology. Routine biochemical tests were determined for patients and controls. GRP78 and CEBPD were measured by enzyme-linked immunosorbent assay. Th17 and Treg cells % and median fluorescent intensity (MFI) were estimated by flow cytometric analysis. Results We found significant increase in Th17 (CD4+ IL-17A+) cells in both % and MFI and significant decrease in CD4+ cells and Treg (CD4+ Foxp3+) cells in both % and MFI in CKD patients compared with controls (P<0.05). Treg (CD4+ Foxp3+) cells % was the lowest in CKD stage 5 patients without dialysis treatment (P<0.05). The changes in Th17 and Treg cells % and MFI led to an increase in the ratio of Th17/Treg cells in CKD patients that was positively correlated with disease stage. Also, we found that serum creatinine was positively correlated with Th17 cell frequency and Th17/Treg cell ratio and negatively correlated with Treg cell frequency. Serum creatinine level was strongly correlated with Th17/Treg ratio than with Th17 or Treg cells. Our study showed a significant increase in GRP78 and CEBPD concentrations in CKD patients compared with healthy individuals and positively correlated with CKD stage. We observed no significant change of GRP78 or CEBPD after hemodialysis. We also found positive correlation of serum creatinine with GRP78 and CEBPD in CKD patients. Lastly, we found that the ratio of Th17/Treg cells was positively correlated with serum GRP78 and CEBPD concentrations. Conclusion Our study confirmed the link between immune dysregulation and ERS in CKD patients. Further studies are needed for proving this link and the new strategy treatment for Treg cells hoping to protect the patients from disease progression and bad outcomes.

Keywords

Chronic kidney disease, endoplasmic reticulum stress, immune disorders, T-helper type 17, regulatory T cells

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