Immunohistochemical Evaluation of Acyl-CoA Synthetase Long-Chain Family Member 4 (ACSL4) Expression in Psoriasis and Its Association with Disease Severity

Acyl-CoA synthetase long-chain family member 4 (ACSL4) is involved in lipid metabolism and has been implicated in ferroptosis-related processes. This study investigated ACSL4 immunoreactivity in psoriatic skin and its association with clinical disease severity. Formalin-fixed, paraffin-embedded skin specimens from 40 patients with psoriasis and 30 healthy controls were evaluated using immunohistochemistry and QuPath-based digital image analysis. ACSL4 immunoreactivity was quantified separately in epidermal and dermal compartments using the percentage of positive cells, mean staining intensity, and a modified staining intensity index (MSII). Between-group comparisons were performed at the specimen level, and associations with Psoriasis Area and Severity Index (PASI) scores were assessed using Spearman correlation analysis. Psoriatic specimens demonstrated significantly higher ACSL4 immunoreactivity than controls in both epidermal and dermal compartments (all p < 0.001). Epidermal MSII values were 46.01 ± 14.53 in patients with psoriasis and 10.95 ± 6.95 in controls, while dermal MSII values were 112.01 ± 20.82 and 8.06 ± 6.87, respectively. ACSL4 staining indices were strongly correlated with PASI scores in the epidermis (rho = 0.755, p < 0.001) and dermis (rho = 0.823, p < 0.001). These findings demonstrate increased ACSL4 immunoreactivity in psoriatic skin and its association with clinical disease severity. However, they do not establish a causal relationship or provide direct evidence of ferroptosis activation.