Molecular dissection of CD28-associated cytokine signaling in early psoriasis

BACKGROUND: Psoriasis is a chronic immune-mediated skin disorder characterized by excessive keratinocyte proliferation and abnormal T-cell activation. Cluster of Differentiation 28 (CD28), a costimulatory protein, plays a crucial role in psoriasis pathophysiology by enhancing T-cell activation and promoting cytokine release. METHODS: A case-control study was involving 168 newly diagnosed psoriasis patients and 159 healthy control individuals (HC), Genotyping of rs1879877 in promoter of CD28 gene was performed using the tetra-primer amplification refractory mutation system-polymerase chain reaction (T-ARMS-PCR), and serum levels of soluble CD28 (sCD28) and selected cytokines (Interleukin (IL), IL-38, IL-39 and Granulocyte Macrophage Colony Stimulating Factor (GM-CSF)) were measured using sandwich enzyme-linked immunosorbent assay (ELISA). RESULTS: The heterozygous GT genotype was predominant among psoriasis patients and was significantly associated with elevated serum sCD28 levels compared to controls, who predominantly carried the wild type GG genotype. Elevated sCD28 levels were linked to increased T-cell activation, contributing to immune dysregulation and disease severity. This was evidenced by increased production of pro-inflammatory cytokines, including IL-39 and GM-CSF, with a concurrent decrease in the anti-inflammatory cytokine IL-38. CONCLUSION: Serum sCD28 levels were significantly elevated in psoriasis patients. The CD28 gene variant rs1879877 (-1198 G/T) appears to be associated with psoriasis pathogenesis, potentially due to increased transcriptional activity that elevates sCD28 expression, thereby influencing T-cell activation and immune modulation.