Clinical, cosmetic and investigational dermatology · 2025
Investigation of the Causal Association Between Treg Cells and Actinic Keratosis Through Two-Sample Mendelian Randomization Analysis.
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Li Huaping, Zhong Jinbao, Bi Chao, Chen Quan, Deng Huiyan, Ou Shanshan, Chen Jiaoquan, Zou Hui, Lin Tianyi, Zhu Huilan
Аннотация
PURPOSE: Actinic keratosis is a highly prevalent precancerous skin condition and a major risk factor for cutaneous squamous cell carcinoma with a significant risk of malignant transformation. Despite its clinical importance, the causal role of immune factors, especially regulatory T (Treg) cells, in actinic keratosis pathogenesis remains unclear. A two-sample Mendelian Randomization (MR) approach was employed to investigate the potential causal link between distinct characteristics of Treg cells and the likelihood of developing actinic keratosis.
PATIENTS AND METHODS: The analysis utilized publicly available genetic data on 167 Treg cell traits and actinic keratosis risk. The Inverse Variance Weighted (IVW) method was the primary analytical approach, supported by MR-Egger, weighted median, and weighted mode analyses. Sensitivity of the findings was assessed through Cochran's Q test, MR-Egger analysis, the MR pleiotropy residual sum and outlier (MR-PRESSO) test, and leave-one-out tests.
RESULTS: The IVW analysis revealed a significant association between resting Treg cell activity and actinic keratosis (OR: 0.9997, p = 0.0420). Additional significant associations included CD39+ resting Treg percentage of CD4 Tregs (OR: 0.9998, p = 0.0123), CD28- double negative (DN) Treg percentage (OR: 0.9995, p = 0.0359), and CD28+ CD45RA- CD8dim Tregs (OR: 1.0002, p = 0.0312). No significant associations were found in supplementary analyses, but sensitivity tests confirmed the reliability of the results.
CONCLUSION: This study suggests a potential causal relationship between certain Treg cell traits and the risk of actinic keratosis, indicating that further research is needed to clarify the underlying mechanisms of this association.
PATIENTS AND METHODS: The analysis utilized publicly available genetic data on 167 Treg cell traits and actinic keratosis risk. The Inverse Variance Weighted (IVW) method was the primary analytical approach, supported by MR-Egger, weighted median, and weighted mode analyses. Sensitivity of the findings was assessed through Cochran's Q test, MR-Egger analysis, the MR pleiotropy residual sum and outlier (MR-PRESSO) test, and leave-one-out tests.
RESULTS: The IVW analysis revealed a significant association between resting Treg cell activity and actinic keratosis (OR: 0.9997, p = 0.0420). Additional significant associations included CD39+ resting Treg percentage of CD4 Tregs (OR: 0.9998, p = 0.0123), CD28- double negative (DN) Treg percentage (OR: 0.9995, p = 0.0359), and CD28+ CD45RA- CD8dim Tregs (OR: 1.0002, p = 0.0312). No significant associations were found in supplementary analyses, but sensitivity tests confirmed the reliability of the results.
CONCLUSION: This study suggests a potential causal relationship between certain Treg cell traits and the risk of actinic keratosis, indicating that further research is needed to clarify the underlying mechanisms of this association.