Hereditary Alpha-Tryptasemia is Associated with Ongoing Symptoms in Individuals with Celiac Disease Despite Following a Gluten-Free Diet.

Abstract

BACKGROUND Hereditary alpha-tryptasemia (HαT) is caused by 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: Prospective cohort of subjects with CeD or non-celiac gluten sensitivity (NCGS) either at diagnosis (Dx), with persisting symptoms on a gluten-free diet (GFD), or in clinical remission. BST levels were determined by immunoassay and tryptase genotyping was performed on gDNA using ddPCR. Duodenal and gastric biopsies were stained for c-KIT, and mast cell (MC) counts were averaged over 5 hpf. RESULTS There were 153 eligible subjects; 13 NCGS and 140 CeD (8 newly Dx patients, 66 with persisting symptoms, 66 in remission). HαT was found in 9 subjects, all symptomatic with CeD (6.4%). One was newly Dx, and the others had persisting symptoms (12.3% of subgroup). Excluding HαT, BST levels were higher among 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. CONCLUSION The prevalence of HαT in CeD is similar to the general population, however, all participants with CeD and HαT had ongoing GI symptoms. Evaluation for HαT should be considered in the management of CeD patients with persisting symptoms.