Molecular and Immune-Mechanism of Keloid Development

Keloids are abnormal scars that grow excessively due to increased fibroblast activity and collagen buildup. They spread beyond the original wound and often come back even after treatment. To find useful biomarkers and treatment targets, we studied immune cells in both blood and scar tissue from a hospital-based group that included 104 keloid patients, 512 healthy individuals, and 100 patients with other scar or inflammatory skin diseases.

Using flow cytometry and single-cell RNA sequencing, we found that CD8+ T cells, which normally help destroy abnormal cells, were greatly reduced in the blood and scar edges of keloid patients. The remaining CD8+ T cells in keloid tissue showed high levels of an inhibitory receptor called NKG2A/CD94, which weakens immune activity. This was linked to increased levels of soluble HLA-E (sHLA-E) in the blood.

Blood tests showed that sHLA-E could identify keloid patients with high accuracy (83.7% sensitivity and 92.2% specificity) and rarely gave false positives in other scar types or skin diseases.

We also examined how patients responded to treatment with triamcinolone and 5-fluorouracil injections. Patients who responded well showed a clear decrease in sHLA-E levels after treatment. In contrast, patients whose sHLA-E levels stayed high were more likely to experience keloid recurrence.

Overall, these findings suggest that the NKG2A/CD94–sHLA-E pathway helps keloids escape immune control. Measuring sHLA-E levels may be useful both for diagnosing keloids and for predicting treatment success. Monitoring sHLA-E in clinical practice could help personalize treatment and reduce the risk of keloid recurrence.