Clinical Medical College, Jiangxi University of Chinese Medicine, Nanchang, China.
Dermatology Department, Affiliated Hospital of Jiangxi University of Chinese Medicine, Nanchang, China.
Skin Res Technol. 2024 Aug;30(8):e13875. doi: 10.1111/srt.13875.
Recent studies increasingly suggest that microbial infections and the immune responses they elicit play significant roles in the pathogenesis of chronic inflammatory skin diseases. This study uses Mendelian randomization (MR) and Bayesian weighted Mendelian randomization (BWMR) to explore the causal relationships between immune antibody responses and four common skin diseases: psoriasis, atopic dermatitis (AD), rosacea, and vitiligo.
We utilized summary statistics from genome-wide association studies (GWAS) for antibody responses to 13 infectious pathogens and four skin diseases. Single nucleotide polymorphisms (SNPs) were selected as instrumental variables (IVs) to assess causal relationships using multiple MR methods, including inverse variance weighted (IVW), MR Egger, and weighted median. BWMR was also employed to confirm findings and address potential pleiotropy.
The IVW analysis identified significant associations between specific antibody responses and the skin diseases studied. Key findings include protective associations of anti-Epstein-Barr virus (EBV) IgG seropositivity and Helicobacter pylori UREA antibody levels with psoriasis and AD. anti-chlamydia trachomatis IgG seropositivity, anti-polyomavirus 2 IgG seropositivity, and varicella zoster virus glycoprotein E and I antibody levels were negatively associated with rosacea, while EBV Elevated levels of the early antigen (EA-D) antibody levels and HHV-6 IE1B antibody levels were positively associated with rosacea. H. pylori Catalase antibody levels were protectively associated with vitiligo, whereas anti-herpes simplex virus 2 (HSV-2) IgG seropositivity was positively associated with vitiligo. The BWMR analysis confirmed these associations.
This study underscores the significant role of H. pylori and other pathogens in these skin diseases, suggesting both protective and exacerbating effects depending on the specific condition. Understanding these pathogen-immune interactions can lead to the development of more effective, personalized treatments and preventative strategies, ultimately improving patient outcomes and quality of life.
越来越多的研究表明，微生物感染及其引发的免疫反应在慢性炎症性皮肤病的发病机制中起着重要作用。本研究采用孟德尔随机化（MR）和贝叶斯加权孟德尔随机化（BWMR）方法，探讨免疫抗体反应与四种常见皮肤疾病（银屑病、特应性皮炎、酒渣鼻和白癜风）之间的因果关系。
我们利用针对 13 种感染性病原体和四种皮肤疾病的抗体反应的全基因组关联研究（GWAS）汇总统计数据。选择单核苷酸多态性（SNP）作为工具变量（IV），使用多种 MR 方法（包括逆方差加权（IVW）、MR Egger 和加权中位数）评估因果关系。还采用 BWMR 来确认发现并解决潜在的多效性问题。
IVW 分析确定了特定抗体反应与所研究皮肤疾病之间的显著关联。主要发现包括抗 EBV IgG 阳性和幽门螺杆菌 UREA 抗体水平与银屑病和特应性皮炎呈保护性关联；抗沙眼衣原体 IgG 阳性、抗多瘤病毒 2 IgG 阳性以及水痘带状疱疹病毒糖蛋白 E 和 I 抗体水平与酒渣鼻呈负相关；EBV 早期抗原（EA-D）抗体水平和 HHV-6 IE1B 抗体水平升高与酒渣鼻呈正相关；幽门螺杆菌过氧化氢酶抗体水平与白癜风呈保护性关联，而抗单纯疱疹病毒 2（HSV-2）IgG 阳性与白癜风呈正相关。BWMR 分析证实了这些关联。
本研究强调了 H. pylori 和其他病原体在这些皮肤疾病中的重要作用，表明根据具体情况，这些病原体-免疫相互作用具有保护和加重作用。了解这些病原体-免疫相互作用可以为开发更有效、个性化的治疗和预防策略提供依据，最终改善患者的预后和生活质量。
