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Abstract：
BACKGROUND: 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.
METHODS: 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.
RESULTS: 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.
CONCLUSIONS: 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.
METHODS: 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.
RESULTS: 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.
CONCLUSIONS: 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.
摘要：
背景：最近的研究表明，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理中起着重要作用。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)来探讨免疫抗体反应与四种常见皮肤病的因果关系:银屑病,特应性皮炎(AD),酒渣鼻,和白癜风。
方法：我们利用全基因组关联研究（GWAS）的汇总统计数据，对13种感染性病原体和4种皮肤病的抗体反应进行分析。选择单核苷酸多态性（SNP）作为工具变量（IVs），以使用多种MR方法评估因果关系。包括逆方差加权(IVW)，Egger先生,和加权中位数。BWMR也被用来确认发现并解决潜在的多效性。
结果：IVW分析确定了特异性抗体应答与所研究的皮肤病之间的显著关联。主要发现包括抗EB病毒（EBV）IgG血清阳性和幽门螺杆菌UREA抗体水平与银屑病和AD的保护性关联。抗沙眼衣原体IgG血清阳性，抗多瘤病毒2IgG血清阳性，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，而EBV升高的早期抗原（EA-D）抗体水平和HHV-6IE1B抗体水平与酒渣鼻呈正相关。幽门螺杆菌过氧化氢酶抗体水平与白癜风保护性相关，而抗单纯疱疹病毒2型（HSV-2）IgG血清阳性与白癜风呈正相关。BWMR分析证实了这些关联。
结论：这项研究强调了幽门螺杆菌和其他病原体在这些皮肤病中的重要作用。表明保护和恶化的影响取决于具体情况。了解这些病原体-免疫相互作用可以导致更有效的发展，个性化治疗和预防策略，最终改善患者的预后和生活质量。
方法：我们利用全基因组关联研究（GWAS）的汇总统计数据，对13种感染性病原体和4种皮肤病的抗体反应进行分析。选择单核苷酸多态性（SNP）作为工具变量（IVs），以使用多种MR方法评估因果关系。包括逆方差加权(IVW)，Egger先生,和加权中位数。BWMR也被用来确认发现并解决潜在的多效性。
结果：IVW分析确定了特异性抗体应答与所研究的皮肤病之间的显著关联。主要发现包括抗EB病毒（EBV）IgG血清阳性和幽门螺杆菌UREA抗体水平与银屑病和AD的保护性关联。抗沙眼衣原体IgG血清阳性，抗多瘤病毒2IgG血清阳性，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，而EBV升高的早期抗原（EA-D）抗体水平和HHV-6IE1B抗体水平与酒渣鼻呈正相关。幽门螺杆菌过氧化氢酶抗体水平与白癜风保护性相关，而抗单纯疱疹病毒2型（HSV-2）IgG血清阳性与白癜风呈正相关。BWMR分析证实了这些关联。
结论：这项研究强调了幽门螺杆菌和其他病原体在这些皮肤病中的重要作用。表明保护和恶化的影响取决于具体情况。了解这些病原体-免疫相互作用可以导致更有效的发展，个性化治疗和预防策略，最终改善患者的预后和生活质量。
