PMID- 33481382 OWN - NLM STAT- MEDLINE DCOM- 20210913 LR - 20231111 IS - 1532-0979 (Electronic) IS - 0147-5185 (Print) IS - 0147-5185 (Linking) VI - 45 IP - 7 DP - 2021 Jul 1 TI - Distinct Small Intestine Mast Cell Histologic Changes in Patients With Hereditary Alpha-tryptasemia and Mast Cell Activation Syndrome. PG - 997-1004 LID - 10.1097/PAS.0000000000001676 [doi] AB - Mast cells (MCs) are important in intestinal homeostasis and pathogen defense but are also implicated in many of the clinical manifestations in disorders such as irritable bowel syndrome. The utility of specific staining for MCs to quantify and phenotype them in intestinal biopsies in patients with gastrointestinal (GI) symptoms is controversial and is not a widely adopted practice. Whether or not intestinal MCs are increased or have a unique phenotype in individuals with hereditary alpha-tryptasemia (HalphaT), who have extra copies of the MC tryptase gene TPSAB1 and typically elevated baseline serum tryptase levels >8 ng/mL is not known. We examined the duodenal biopsies of 17 patients with HalphaT and compared them to 15 patients with mast cell activation syndrome who had baseline serum tryptases <8 ng/mL (MCAS-NT) and 12 GI-controls. We determined that the HalphaT subjects had increased MCs in the duodenum compared with MCAS-NT and GI-controls (median=30.0; interquartile range [IQR]: 20.0 to 40.0 vs. median=15.0; IQR: 5.00 to 20.0; P=0.013 and median=15.0; IQR: 13.8 to 20.0; P=0.004, respectively). These MCs were significantly found in clusters (<15 MCs) and were located throughout the mucosa and submucosa including the superficial villi compared with MCAS-NT and GI-control patients. Spindle-shaped MCs were observed in all groups including controls. These data demonstrate that HalphaT is associated with increased small intestinal MCs that may contribute to the prevalent GI manifestations observed among individuals with this genetic trait. CI - Copyright (c) 2021 Wolters Kluwer Health, Inc. All rights reserved. FAU - Hamilton, Matthew J AU - Hamilton MJ AD - Division of Gastroenterology, Hepatology, and Endoscopy. FAU - Zhao, Melissa AU - Zhao M AD - Departments of Pathology. FAU - Giannetti, Matthew P AU - Giannetti MP AD - Division of Allergy and Clinical Immunology, Mastocytosis Center. FAU - Weller, Emily AU - Weller E AD - Division of Allergy and Clinical Immunology, Mastocytosis Center. FAU - Hufdhi, Raied AU - Hufdhi R AD - Division of Allergy and Clinical Immunology, Mastocytosis Center. FAU - Novak, Peter AU - Novak P AD - Neurology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA. FAU - Mendoza-Alvarez, Lybil B AU - Mendoza-Alvarez LB AD - Department of Pediatrics, Division of Pediatric Gastroenterology. FAU - Hornick, Jason AU - Hornick J AD - Departments of Pathology. FAU - Lyons, Jonathan J AU - Lyons JJ AD - Laboratory of Allergic Diseases, National Institute of Allergy and Infectious Diseases, Bethesda, MD. FAU - Glover, Sarah C AU - Glover SC AD - Department of Medicine, Division of Gastroenterology, University of Florida, Gainesville, FL. AD - Department of Medicine, Division of Digestive Diseases, University of Mississippi Medical Center, Jackson, MI. FAU - Castells, Mariana C AU - Castells MC AD - Division of Allergy and Clinical Immunology, Mastocytosis Center. FAU - Pozdnyakova, Olga AU - Pozdnyakova O AD - Departments of Pathology. LA - eng GR - R21 TR002639/TR/NCATS NIH HHS/United States PT - Comparative Study PT - Journal Article PT - Multicenter Study PT - Research Support, N.I.H., Extramural PT - Research Support, N.I.H., Intramural PT - Research Support, Non-U.S. Gov't PL - United States TA - Am J Surg Pathol JT - The American journal of surgical pathology JID - 7707904 RN - EC 3.4.21.59 (TPSAB1 protein, human) RN - EC 3.4.21.59 (Tryptases) SB - IM MH - Adult MH - Aged MH - Boston MH - Duodenum/*pathology MH - Female MH - Florida MH - Gastrointestinal Diseases/blood/genetics/*pathology MH - Genetic Predisposition to Disease MH - *Genetic Variation MH - Humans MH - Intestinal Mucosa/pathology MH - Male MH - Mast Cells/*pathology MH - Mastocytosis/blood/genetics/*pathology MH - Middle Aged MH - Phenotype MH - Retrospective Studies MH - Tryptases/blood/*genetics PMC - PMC8192345 MID - NIHMS1658539 COIS- Conflicts of Interest and Source of Funding: Supported in part by a combined grant from the Mastocytosis Society and American Academy of Allergy, Asthma, and Immunology (M.J.H.), the Gatorade Trust through funds distributed by the University of Florida, Department of Medicine (S.C.G.), extramural NIH fund 1R21TR002639-01A1 (M.J.H. and S.C.G.), and the Division of Intramural Research of the National Institute of Allergy and Infectious Diseases, NIH (J.J.L.). The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products, or organizations imply endorsement by the US Government. The authors have disclosed that they have no significant relationships with, or financial interest in, any commercial companies pertaining to this article. EDAT- 2021/01/23 06:00 MHDA- 2021/09/14 06:00 PMCR- 2022/07/01 CRDT- 2021/01/22 13:41 PHST- 2021/01/23 06:00 [pubmed] PHST- 2021/09/14 06:00 [medline] PHST- 2021/01/22 13:41 [entrez] PHST- 2022/07/01 00:00 [pmc-release] AID - 00000478-202107000-00014 [pii] AID - 10.1097/PAS.0000000000001676 [doi] PST - ppublish SO - Am J Surg Pathol. 2021 Jul 1;45(7):997-1004. doi: 10.1097/PAS.0000000000001676.