ABSTRACT
Keloids are problematic scars characterized by excessive fibroblast proliferation and collagen deposition that extend beyond the original wound and often recur after treatment. To idennfy clinically actionable biomarkers and therapeutic targets, we conducted immune profiling on both blood and lesional tissue £rom a hospital —based cohort (104 keloid patient, 512 healthy controls, 100 patients with other scar or inflammatory skin conditions). Flow cytometry and single —cell RNA sequencing revealed a significant depletion of cytotoxic CD8+ T lymphocytes (CTLs) in peripheral blood and within keloid margins. In the scar tissue, residual CTLs displayed high expression of the inhibitory NKG2A/CD94 receptor complex, which corresponded with elevated serum levels of soluble I-ILA —E (sHLA —E). Quantitative assays demonstrated that sI-lLA —E distinguished keloid patients with 85.7% sensitivity and 92.2% specificity, showing minimal cross—reactivity in hypertrophic scars or urirelated derrnatologic diseases.
We then assessed response to combined intralesional triamcinolone and 5 — fiuorouracil therapy in a treatment subgroup. Patients with favorable outcomes exhibited pronounced reductions in sHLA —E post —treatment, whereas incomplete suppression of sHLA—E was linked to higher recurrence rates on follow—up. These resula implicate the NKG2n/CD94 sHLA—E axis in immune evasion within keloid pathology and position sHLA —E as both a diagnostic marker for keloid risk and a prognostic indicator of treatment efficacy. Incorporating sHLA—E monitoring into clinical practice could enable personalized strategies to prevent keloid fomiation and recurrence.