Elevated Basal Serum Tryptase: Disease Distribution and Variability in a Regional Health System

Aubri M Waters; Hyun J Park; Andrew L Weskamp; Allyson Mateja; Megan E Kachur; Jonathan J Lyons; Benjamin J Rosen; Nathan A Boggs

doi:10.1016/j.jaip.2021.12.031

Elevated Basal Serum Tryptase: Disease Distribution and Variability in a Regional Health System

J Allergy Clin Immunol Pract. 2022 Sep;10(9):2424-2435.e5. doi: 10.1016/j.jaip.2021.12.031. Epub 2022 Jan 12.

Authors

Aubri M Waters¹, Hyun J Park¹, Andrew L Weskamp², Allyson Mateja³, Megan E Kachur⁴, Jonathan J Lyons⁵, Benjamin J Rosen⁶, Nathan A Boggs⁷

Affiliations

¹ Allergy and Immunology Service, Walter Reed National Military Medical Center, Bethesda, Md.
² Internal Medicine Service, Walter Reed National Military Medical Center, Bethesda, Md.
³ Clinical Monitoring Research Program Directorate, Frederick National Laboratory for Cancer Research, Frederick, Md.
⁴ Department of Pathology, Walter Reed National Military Medical Center, Bethesda, Md.
⁵ Laboratory of Allergic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Md.
⁶ Hematopathology Service, Walter Reed National Military Medical Center, Bethesda, Md.
⁷ Allergy and Immunology Service, Walter Reed National Military Medical Center, Bethesda, Md; Department of Medicine, Uniformed Services University, Bethesda, Md. Electronic address: nathan.a.boggs3.mil@mail.mil.

Abstract

Background: Hereditary-alpha tryptasemia (HαT) is the most common etiology for elevated basal serum tryptase (BST). However, the utility of tryptase genotyping of individuals with elevated BST in general clinical practice remains undefined. Moreover, studies showing associations between elevated BST and chronic kidney disease (CKD), myelodysplastic syndrome (MDS), rheumatoid arthritis, or eosinophilic esophagitis did not include tryptase genotyping.

Objective: To determine the utility of tryptase genotyping among individuals with moderate elevations in BST at a regional health system.

Methods: Clinical and laboratory data from 109 subjects with basal tryptase values of 7.5 ng/mL or greater who were tested for HαT or had a disorder previously linked to elevated BST were collected retrospectively by chart review.

Results: Fifty-eight subjects had elevated BST defined as 11.5 ng/mL or greater. HαT was found in 63.8% (n = 37), 12.1% (n = 7) had CKD, and 20.7% (n = 12) had clonal myeloid disorders. A total of 6.9% (n = 4) with elevated BST had negative testing for HαT, CKD, and myeloid neoplasms. Two subjects with CKD, 1 subject with MDS, and 1 with myeloid hypereosinophilic syndrome had negative testing for HαT. Among subjects with elevated BST and more than 1 tryptase measurement, 41.5% (n = 22) had BST variability that exceeded the 20% plus 2 formula. Increased BST variability was found in subjects with HαT, all forms of mastocytosis, CKD, MDS, and those with no associated diagnosis.

Conclusions: HαT, CKD, and clonal myeloid disorders or a combination of the 3 constitute approximately 90% of individuals with elevated BST in clinical practice. Myeloid neoplasms were over-represented in this cohort relative to population prevalence data suggesting tryptase measurement selection bias by clinicians or higher prevalence. Elevated BST is associated with increased tryptase variability, regardless of etiology.

Keywords: Biomarkers; Chronic kidney disease; Disease distribution; Elevated basal tryptase algorithm; Hereditary-alpha tryptasemia; Mastocytosis; Myeloid neoplasms; Tryptase; Variability.

Published by Elsevier Inc.

Publication types

Research Support, N.I.H., Extramural

MeSH terms

Humans
Mast Cells
Mastocytosis / diagnosis
Myelodysplastic Syndromes / diagnosis
Renal Insufficiency, Chronic* / diagnosis
Retrospective Studies
Tryptases* / blood

Substances

Tryptases

Grants and funding

Z99 AI999999/ImNIH/Intramural NIH HHS/United States