Therrien Amelie, Akula Srihitha, Galeas-Pena Michelle, Frank Emma, Gillette Lily, Silvester Jocelyn A, Leffler Daniel A, Galvez Javier Villafuerte, Kelly Ciaran P, Pozdnyakova Olga, Glover Sarah, Lyons Jonathan J
Celiac Center, Department of Gastroenterology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, USA.
Department of Medicine, Section of Gastroenterology, Tulane University, Louisiana, USA.
Am J Gastroenterol. 2025 May 14. doi: 10.14309/ajg.0000000000003537.
Hereditary alpha-tryptasemia (HαT) is caused by the increased copy number of TPSAB1 when encoding for alpha-tryptase, resulting in elevated basal serum tryptase (BST). Many affected individuals report irritable bowel syndrome-like and reflux symptoms. We aimed to assess the prevalence of HαT in celiac disease (CeD) and whether this genetic trait modifies disease course.
This study included a prospective cohort of subjects with CeD or nonceliac gluten sensitivity (NCGS) either at diagnosis (Dx), with persisting symptoms on a gluten-free diet, or in clinical remission. BST levels were determined by immunoassay, and tryptase genotyping was performed on genomic DNA using digital droplet polymerase chain reaction (PCR) [ddPCR]. Duodenal and gastric biopsies were stained for c-KIT, and mast cell (MC) counts were averaged over 5 high power field (hpf).
There were 153 eligible subjects: 13 with NCGS and 140 with CeD (8 patients with new Dx, 66 with persisting symptoms, 66 in remission). HαT was found in 9 subjects, all symptomatic with CeD (6.4%). One was new Dx, and the others had persisting symptoms (12.3% of subgroup). Excluding HαT, BST levels were higher among patients with CeD vs NCGS (median 5.4 vs 3.9 mcg/L P < 0.05). Duodenal MC counts were higher in CeD vs controls ( P < 0.05) and 24% higher in those with HαT (median HαT CeD 27.3/hpf, non-HαT CeD 22.0/hpf, controls 18.4/hpf). MC counts did not differ based on villous atrophy or clinical presentation.
The prevalence of HαT in CeD is similar to the general population; however, all participants with CeD and HαT had ongoing gastrointestinal (GI) symptoms. Evaluation for HαT should be considered in the management of patients with CeD and persisting symptoms.
遗传性α-类胰蛋白酶血症（HαT）是由编码α-胰蛋白酶的TPSAB1拷贝数增加引起的，导致基础血清类胰蛋白酶（BST）升高。许多受影响的个体报告有肠易激综合征样症状和反流症状。我们旨在评估腹腔疾病（CeD）中HαT的患病率，以及这种遗传特征是否会改变疾病进程。
本研究纳入了一组前瞻性队列研究对象，这些对象患有CeD或非腹腔麸质敏感（NCGS），包括诊断时、采用无麸质饮食后仍有持续症状或处于临床缓解期的患者。通过免疫测定法测定BST水平，并使用数字液滴聚合酶链反应（PCR）[ddPCR]对基因组DNA进行类胰蛋白酶基因分型。对十二指肠和胃活检组织进行c-KIT染色，并在5个高倍视野（hpf）上平均肥大细胞（MC）计数。
共有153名符合条件的研究对象：13名患有NCGS，140名患有CeD（8名新诊断患者，66名有持续症状患者，66名处于缓解期患者）。9名研究对象被发现患有HαT，所有患者均为有症状的CeD患者（6.4%）。1名是新诊断患者，其他患者有持续症状（占该亚组的12.3%）。排除HαT后，CeD患者的BST水平高于NCGS患者（中位数分别为5.4与3.9 mcg/L，P < 0.05）。CeD患者的十二指肠MC计数高于对照组（P < 0.05），患有HαT的患者十二指肠MC计数高24%（HαT CeD患者中位数为27.3/hpf，非HαT CeD患者为22.0/hpf，对照组为18.4/hpf）。MC计数在绒毛萎缩或临床表现方面无差异。
CeD中HαT的患病率与一般人群相似；然而，所有患有CeD和HαT的参与者都有持续的胃肠道（GI）症状。在管理有持续症状的CeD患者时应考虑对HαT进行评估。
