Zhu Haoqi, Pan Jingyi
Department of Gastroenterology, Wenzhou Central Hospital, The Dingli Clinical Institute of Wenzhou Medical University, Wenzhou, 325000, Zhejiang, China.
Department of Anesthesiology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325000, Zhejiang, China.
Arch Dermatol Res. 2025 Jan 6;317(1):176. doi: 10.1007/s00403-024-03736-0.
Although the precise cause of the co-occurrence of pyoderma gangrenosum (PG) and inflammatory bowel disease (IBD) is still unknown, prior research has shown that the two conditions coexist. Moreover, it is currently unknown how immune cells function in influencing the relationship between IBD and PG.
In order to choose independent single nucleotide polymorphism (SNP) as instrumental variables, we were provided with genome-wide association study (GWAS) summary data of European populations from the IEU OpenGWAS project (for IBD) and a the FinnGen database (for PG) publically available. For the MR analysis, a range of analytical techniques were employed to peer into the possible causative relationship between PG and IBD. The two-step MR analysis was used to investigate the mediating role of immune cells between IBD and PG. The chief method utilized was the inverse variance weighted (IVW) approach. Using the Cochran's Q test and the MR-Egger intercept, respectively, heterogeneity or pleiotropy was evaluated to support the findings. MR-PRESSO (Mendelian Randomization Pleiotropy RESidual Sum and Outlier) were used to identify the outlier SNP.
IBD was found to raise the incidence of PG (IVW-FE: OR = 1.604, 95%CI = 1.308-1.966, p = 5.58 × 10), according to MR findings. Moreover, UC or CD were strongly correlated with a greater risk of PG (OR = 1.339, 95%CI = 1.041-1.723, p = 0.023 for UC; OR = 1.339, 95%CI = 1.107-1.621, p = 0.003 for CD). The results of the reverse MR study did not suggest a connection between PG and IBD. CD4 regulatory T cell is the mediator that particularly stood out in the interaction between UC and PG. There was evidence of neither heterogeneity nor horizontal pleiotropy. And the validity of these conclusions was verified.
In the European population, PG risk may be genetically elevated by IBD, including CD and UC, according to the current study. The effect of UC on PG may have been causally mediated by CD4 regulatory T cells.
尽管坏疽性脓皮病（PG）与炎症性肠病（IBD）同时出现的确切原因尚不清楚，但先前的研究表明这两种疾病并存。此外，目前尚不清楚免疫细胞在影响IBD与PG之间的关系中如何发挥作用。
为了选择独立的单核苷酸多态性（SNP）作为工具变量，我们获得了来自IEU OpenGWAS项目（针对IBD）的欧洲人群全基因组关联研究（GWAS）汇总数据以及公开可用的芬兰基因数据库（针对PG）。对于孟德尔随机化（MR）分析，采用了一系列分析技术来探究PG与IBD之间可能的因果关系。采用两步MR分析来研究免疫细胞在IBD和PG之间的中介作用。主要使用的方法是逆方差加权（IVW）法。分别使用 Cochr an's Q检验和MR-Egger截距来评估异质性或多效性以支持研究结果。使用MR-PRESSO（孟德尔随机化多效性残差和异常值）来识别异常SNP。
根据MR研究结果，发现IBD会增加PG的发病率（IVW-FE：OR = 1.604，95%CI = 1.308 - 1.966，p = 5.58×10）。此外，溃疡性结肠炎（UC）或克罗恩病（CD）与PG风险增加密切相关（UC的OR = 1.339，95%CI = 1.041 - 1.723，p = 0.023；CD的OR = 1.339，95%CI = 1.107 - 1.621，p = 0.003）。反向MR研究结果未表明PG与IBD之间存在关联。CD4调节性T细胞是在UC与PG相互作用中特别突出的中介因素。没有异质性或水平多效性的证据。并且这些结论的有效性得到了验证。
根据当前研究，在欧洲人群中，IBD（包括CD和UC）可能会通过基因方式增加PG风险。UC对PG的影响可能是由CD4调节性T细胞因果介导的。
