Objective: Childhood-onset systemic lupus erythematosus (cSLE) is usually a more severe and aggressive disease than adult-onset SLE (aSLE), but cellular and subcellular reasons for these differences ...are not well understood. The present study analysed T helper lymphocyte (Th) subsets, STAT1/STAT5 signalling response and cytokine profiles of cSLE. Methods: FOXP3+ regulatory (Treg) and effector Th subsets, expression and phosphorylation of STAT1/STAT5 in Th and cytokine profiles were measured in the peripheral blood of cSLE patients and healthy controls (HC), using flow cytometry and immunoassay on a biochip. Results: Significant correlation between expression of the activation marker HLA-DR and decreased Th counts, an increase in the percentage of FOXP3+Th, and a decrease in the activated Treg (aTreg) subset among them were found in cSLE. In contrast to our previous findings in aSLE, no significant differences in percentages and a significant decrease in the numbers of the naïve-resting Treg (rTreg) subset compared to HC were found. The percentages of CD25-cells, possibly reflecting IL-2 depletion, were significantly increased in cSLE aTreg, but not in the rTreg subset. Consistent with the results of our previous studies in aSLE, increased expression of STAT1, along with significant correlation between decreased Th counts and their increased basal phosphorylation of STAT5, was also found in cSLE. Conclusion: Our results suggest that the key difference in Treg homeostasis between cSLE and aSLE is in the rTreg subset. However, perturbed aTreg homestasis, increased levels of STAT1 protein, and homeostatic STAT5 signalling appear to be intrinsic characteristics of the disease, present in cSLE and aSLE alike.
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