Thesis (Ph.D.) - Cairo University - Faculty of Medicine - Department of Dermatology and Venerology

Background: Spleen tyrosine kinase (Syk) and zeta-chain-associated protein kinase 70 kDa (ZAP-70) are tyrosine kinases (TKs) of the same family. It was proposed the Syk may have a role in interleukin (IL)-17 signaling, mediating the production of chemokine (C-C motif) ligand 20 (CCL20). ZAP-70 is a key regulator of T cell receptor (TCR) signaling, and is critical for proper T cell proliferation, differentiation, and effector function. Objective: Our aim was to study the degree of expression of Syk and ZAP-70 and its relation to clinical disease parameters as well as Syk's relation to CCL20 in psoriatic skin and serum. Methods: Twenty psoriatic patients and twenty age, sex and skin type matched controls were included. Full clinical examination was done and tissue and serum levels of phosphorylated Syk, phosphorylated ZAP-70 and CCL20 were measured by ELISA. Results: Syk was downregulated in psoriatic skin and serum in comparison to controls. However, these results only reached a statistical significance in serum (P=0.001). ZAP-70 levels were also significantly lower in both patients' skin (P=0.007) and serum (P=0.035) when compared to controls. CCL20 levels were significantly higher in patients when compared to controls, in both tissue (P=0.026), and serum (P=0.045), but had no detectable correlation with Syk. Conclusion: We suggest that SyK may play paradoxical roles in inflammation depending on the stimulating ligand and the surrounding cytokine milieu. We also II speculate that the aberrant ZAP-70 expression may be instrumental in the process of autoimmunity

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