Introduction:
CKD-aP is a prevalent and very burdensome comorbidity associated with CKD, and its etiopathogenesis is not fully understood. Recent studies support the possible contribution of serum IL-31 to the pathogenesis of itch in hemodialysis patients. In particular, Th2 cytokines, including interleukin IL-4, IL-5, IL-13, and IL-31 which contribute to the symptoms of chronic inflammation and pruritus in atopic dermatitis, psoriasis, and prurigo nodularis. We designed the study to check the role of IL-31 mediated JAK-STAT pathway in the pathogenesis of CKD-aP patients and whether JAK inhibitors can be a potential target for treating pruritus in CKD-aP
Methods:
CKD-aP patients with moderate to severe itch (n=30) and healthy controls (HC n=20 ) were recruited for the study. A 2 mm skin punch biopsy was collected and processed for RNA isolation, cDNA synthesis, and qRTPCR experiment to check the expression of IL-31 cytokine, IL31 receptor-alpha, OSMR-beta receptor, JAK1, JAK2, STAT1, STAT3 and STAT 5 expression in the skin of CKD-aP patients vs healthy control. Relative fold change in the gene expression was measured by the ddCt method. Moreover, 3 ml of blood in a plain vial was collected for serum isolation and IL-31 cytokine levels were detected in the serum of CKD-aP patients vs HC by ELISA
Results:
The mean age of recruited patients and HC were (55±10 years) and (42±6) years respectively. The itch intensity score measured by NRS was 9±3.5 in CKD-ap patients. Relative fold change in expression of IL-31 cytokine was 2.74 fold higher in skin pf CKD-aP patients than controls. Similarly, the fold change in expression of IL-31R and OSM receptor was significantly upregulated in patients (IL-31R; CKD-aP 1.29 >1HC) (OSMR; CKD-aP 8.12 >1 HC). The expression of JAK-STAT pathway genes related to IL-6 family of cytokines which includes IL-31 cytokine were also found to be increased in skin of CKD-aP patients in comparison to the HC. (JAK-1; CKD-aP 1.3>1 HC) ,(JAK-2; CKD-aP 1.72>1 HC), (STAT-1 ; CKD-aP 1.86>1 HC), (STAT-3 ; CKD-aP 3.51>1 HC) and (STAT-5 ; CKD-aP 1.97>1 HC). Also, the serum levels of IL-31 was also found to be higher in CKD-aP patients than healthy controls.
Conclusions:
The expression of IL-31 cytokine along with its heterodimeric receptors was found to be higher in skin of CKD-aP patients comparison to control. Serum IL-31 levels were also high. IL-31 mediated pruriogenetic sensations through JAK-STAT signaling was found to be well associated in CKD-ap patients as like in AD. So, JAK-inhibitors may serve as good choice for treating itch in CKD-ap patients. Further this study needs to validated on large population.
I have no potential conflict of interest to disclose.
I did not use generative AI and AI-assisted technologies in the writing process.