Division of Newborn Medicine, Boston Children's Hospital, Boston, Mass; Department of Pediatrics, Children's Hospital of UPMC, Pittsburgh, Pa; Department of Pediatrics, Yale University School of Medicine, New Haven, Conn.
Division of Digestive Diseases, Department of Medicine, University of Mississippi Medical Center, Jackson, Miss.
J Allergy Clin Immunol. 2021 Sep;148(3):813-821.e7. doi: 10.1016/j.jaci.2021.04.004. Epub 2021 Apr 15.
Hereditary alpha-tryptasemia (HαT) is characterized by elevated basal serum tryptase due to increased copies of the TPSAB1 gene. Individuals with HαT frequently present with multisystem complaints, including anaphylaxis and seemingly functional gastrointestinal (GI) symptoms.
We sought to determine the prevalence of HαT in an irritable bowel syndrome cohort and associated immunologic characteristics that may distinguish patients with HαT from patients without HαT.
Tryptase genotyping by droplet digital PCR, flow cytometry, cytometry by time-of-flight, immunohistochemistry, and other molecular biology techniques was used.
HαT prevalence in a large irritable bowel syndrome cohort was 5% (N = 8/158). Immunophenotyping of HαT PBMCs (N ≥ 27) revealed increased total and class-switched memory B cells. In the small bowel, expansion of tissue mast cells with expression of CD203c, HLA-DR, and FcεRI, higher intestinal epithelial cell pyroptosis, and increased class-switched memory B cells were observed. IgG profiles in sera from individuals with HαT (N = 21) significantly differed from those in individuals with quiescent Crohn disease (N = 20) and non-HαT controls (N = 19), with increased antibodies directed against GI-associated proteins identified in individuals with HαT.
Increased mast cell number and intestinal epithelial cell pyroptosis in the small intestine, and class-switched memory B cells in both the gut and peripheral blood associated with IgG reactive to GI-related proteins, distinguish HαT from functional GI disease. These innate and adaptive immunologic findings identified in association with HαT are suggestive of subclinical intestinal inflammation in symptomatic individuals.
遗传性α-胰蛋白酶血症（HαT）的特征是由于 TPSAB1 基因的拷贝数增加，导致基础血清胰蛋白酶升高。HαT 患者常出现多系统症状，包括过敏反应和看似功能性胃肠道（GI）症状。
我们旨在确定遗传性α-胰蛋白酶血症在肠易激综合征患者中的患病率，以及可能将 HαT 患者与无 HαT 患者区分开来的相关免疫学特征。
采用液滴数字 PCR、流式细胞术、飞行时间细胞术、免疫组织化学和其他分子生物学技术进行胰蛋白酶基因分型。
在一个大型肠易激综合征患者队列中，HαT 的患病率为 5%（N=158 例中的 8 例）。对 HαT PBMCs（N≥27）的免疫表型分析显示，总和类别转换记忆 B 细胞增加。在小肠中，观察到组织肥大细胞的扩增，表达 CD203c、HLA-DR 和 FcεRI，肠上皮细胞焦亡增加，以及类别转换记忆 B 细胞增加。来自 HαT 个体（N=21）的血清 IgG 谱与处于静止期克罗恩病（N=20）和非 HαT 对照个体（N=19）的 IgG 谱显著不同，在 HαT 个体中发现了针对与 GI 相关蛋白的增加的抗体。
小肠中肥大细胞数量增加和肠上皮细胞焦亡，以及与 GI 相关蛋白反应的 IgG 相关的肠道和外周血中的类别转换记忆 B 细胞，将 HαT 与功能性 GI 疾病区分开来。与 HαT 相关的这些先天和适应性免疫发现提示有症状个体存在亚临床肠道炎症。
