Department of Medicine, Division of Gastroenterology, Hepatology and Nutrition, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, United States.
Department of Medicine, Division of Gastroenterology and Hepatology, Mayo Clinic Health System, Eau Claire, Wisconsin, United States.
Inflamm Bowel Dis. 2021 May 17;27(6):855-863. doi: 10.1093/ibd/izaa230.
Immunoglobulin G subclass 4 (IgG4) is hypothesized to play an immunomodulatory role, downregulating humoral immune responses. The role of this anti-inflammatory molecule in inflammatory bowel disease (IBD) has not been fully characterized. We sought to define alterations in serum IgG4 in patients with IBD and their association with multiyear disease severity.
We analyzed metadata derived from curated electronic health records from consented patients with IBD prospectively followed at a tertiary center over a 10-year time period. Patients with IBD with IgG4 serum levels available formed the study population. Demographics and multiyear clinical data were collected and analyzed. We stratified patients with IBD with low, normal, or high serum IgG4 levels.
We found IgG4 characterized in 1193 patients with IBD and low IgG4 levels in 233 patients (20%) and elevated IgG4 levels in 61 patients (5%). An IgG4 deficiency did not significantly correlate with other antibody deficiencies. In a multiple Poisson regression analysis, low IgG4 was associated with more years on biologic agents (P = 0.002) and steroids (P = 0.049) and more hospital admissions (P < 0.001), clinic visits (P = 0.010), outpatient antibiotic prescriptions (P < 0.001), and CD-related surgeries (P = 0.011) during the study period after controlling for certain confounders. Elevated IgG4 was only associated with primary sclerosing cholangitis (P = 0.011). A cohort of patients with IgG4-deficient severe IBD received intravenous Ig replacement therapy, which benefited and was continued in 10 out of 11 individuals.
An IgG4 subclass deficiency, distinct from other antibody deficiencies, occurred commonly in a referral IBD population and was associated with multiple markers of disease severity. This is the first association of IgG4 subclass deficiency with an inflammatory disease process. Further work is needed to define the mechanistic role of IgG4 deficiency in this severe IBD subgroup.
免疫球蛋白 G 亚类 4（IgG4）被认为具有免疫调节作用，可以下调体液免疫反应。这种抗炎分子在炎症性肠病（IBD）中的作用尚未完全确定。我们旨在确定 IBD 患者血清 IgG4 的变化及其与多年疾病严重程度的关系。
我们分析了来自一家三级中心接受前瞻性随访的 IBD 患者的经审核电子健康记录元数据，随访时间为 10 年。形成研究人群的是具有 IgG4 血清水平的 IBD 患者。收集并分析了人口统计学和多年临床数据。我们对 IgG4 血清水平低、正常或高的 IBD 患者进行了分层。
我们在 1193 例 IBD 患者中发现了 IgG4 特征，其中 233 例（20%）患者 IgG4 水平低，61 例（5%）患者 IgG4 水平高。IgG4 缺乏与其他抗体缺乏无显著相关性。在多元泊松回归分析中，低 IgG4 与生物制剂（P=0.002）和类固醇（P=0.049）使用时间更长、住院次数更多（P<0.001）、就诊次数（P=0.010）、门诊抗生素处方（P<0.001）以及 CD 相关手术（P=0.011）有关，这是在控制某些混杂因素后研究期间的结果。高 IgG4 仅与原发性硬化性胆管炎（PSC）有关（P=0.011）。一组 IgG4 缺乏的严重 IBD 患者接受了静脉注射免疫球蛋白替代治疗，其中 11 例中的 10 例受益并继续接受治疗。
在一个 IBD 患者的转诊人群中，与其他抗体缺乏不同，IgG4 亚类缺乏很常见，与多种疾病严重程度标志物有关。这是 IgG4 亚类缺乏与炎症性疾病过程的首次关联。需要进一步研究以确定 IgG4 缺乏在这一严重 IBD 亚组中的机制作用。
