Medical College of Nanchang University, Nanchang, China.
Department of Hematology, Jiangxi Provincial People's Hospital, The First Affiliated Hospital of Nanchang Medical College, Nanchang, China.
Front Immunol. 2023 Sep 11;14:1248325. doi: 10.3389/fimmu.2023.1248325. eCollection 2023.
IgA vasculitis (IgAV) is an immune-associated vasculitis, yet its exact etiology remains unclear. Here, we explore the interaction between IgAV and inflammatory factors using bidirectional Mendelian randomization (MR).
We conducted a bidirectional summary-level MR analysis to delineate the causality of C-reactive protein (CRP), procalcitonin (PCT), and 41 circulating inflammatory regulators with IgAV. Data on genetic variants related to inflammation were obtained from three genome-wide association studies (GWASs) on CRP, PCT, and human cytokines, whereas data on IgAV was from large meta-analyses of GWAS among 216 569 FinnGen Biobank participants. The primary MR analysis was performed using the inverse-variance weighted (IVW) approach, and the sensitivity analyses were carried out using MR-Egger, weighted median, weighted mode, and MR-pleiotropy residual sum and outlier.
This study revealed the association of CRP higher levels with increased risk of IgAV through IVW method (Estimate odds ratio [OR] = 1.41, 95% confidence interval [CI]: 1.01-1.98, = 0.04), MR-Egger (OR = 1.87, CI: 1.15-3.02, = 0.01), weighted median (OR = 2.00, CI: 1.21-3.30, = 0.01) and weighted mode (OR = 1.74, CI: 1.13-2.68, = 0.02). Furthermore, elevated IL-8 was strongly implicated with a higher risk of IgAV (IVW OR = 1.42, CI: 1.05-1.92; = 0.02). Conversely, genetically predicted IgAV was associated with decreased levels of TNF-β (IVW estimate = -0.093, CI: -0.178 - -0.007; = 0.033). Additionally, no such significant statistical differences for other inflammatory factors were found.
Our current study using bidirectional MR analysis provides compelling evidence for a causal effect of CRP, PCT, and circulating inflammatory regulators on IgAV. These findings contribute to a better understanding of the pathogenesis of IgAV and emphasize the potential of targeting inflammatory factors for therapeutic interventions.
IgA 血管炎（IgAV）是一种免疫相关性血管炎，但确切病因仍不清楚。在这里，我们使用双向 Mendelian 随机化（MR）研究 IgAV 与炎症因子之间的相互作用。
我们进行了双向汇总水平 MR 分析，以描绘 C 反应蛋白（CRP）、降钙素原（PCT）和 41 种循环炎症调节因子与 IgAV 的因果关系。与炎症相关的遗传变异数据来自 CRP、PCT 和人类细胞因子的三项全基因组关联研究（GWAS），而 IgAV 数据来自 216569 名芬兰基因生物库参与者的 GWAS 大型荟萃分析。主要 MR 分析采用逆方差加权（IVW）方法进行，敏感性分析采用 MR-Egger、加权中位数、加权模式和 MR 偏倚残差和异常值进行。
本研究通过 IVW 方法发现 CRP 水平升高与 IgAV 风险增加相关（估计比值比 [OR] = 1.41，95%置信区间 [CI]：1.01-1.98， = 0.04），MR-Egger（OR = 1.87，CI：1.15-3.02， = 0.01），加权中位数（OR = 2.00，CI：1.21-3.30， = 0.01）和加权模式（OR = 1.74，CI：1.13-2.68， = 0.02）。此外，升高的白细胞介素 8 与 IgAV 风险增加密切相关（IVW OR = 1.42，CI：1.05-1.92； = 0.02）。相反，遗传预测的 IgAV 与 TNF-β 水平降低相关（IVW 估计值 = -0.093，CI：-0.178 - -0.007； = 0.033）。此外，对于其他炎症因子，没有发现具有统计学意义的差异。
本研究使用双向 MR 分析为 CRP、PCT 和循环炎症调节因子对 IgAV 的因果关系提供了有力证据。这些发现有助于更好地了解 IgAV 的发病机制，并强调了靶向炎症因子治疗干预的潜力。
