Hereditary Alpha-Tryptasemia Is Associated With Ongoing Symptoms in Individuals With Celiac Disease Despite Following a Gluten-free Diet

Abstract

Introduction: 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.

Methods: 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).

Results: 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.

Discussion: 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.

Keywords: celiac disease; hereditary alpha-tryptasemia; mast cells; non-responsive celiac disease.