Routine KIT p.D816V screening identifies clonal mast cell disease in patients with Hymenoptera allergy regularly missed using baseline tryptase levels alone - 04/08/21
Abstract |
Background |
Clonal mast cell disorders and elevated basal serum tryptase (BST) levels with unknown cause(s) are associated with severe Hymenoptera venom–triggered anaphylaxis (HVA). However, some individuals with clonal disease have a normal BST level (<11.4 ng/mL).
Objective |
Our aim was to evaluate whether screening for KIT p.D816V in the blood is a useful clinical tool to risk-stratify patients with venom allergy.
Methods |
We prospectively recruited 374 patients with Hymenoptera allergy and no overt signs of mastocytosis who were referred to our center during the years 2018 and 2019. KIT p.D816V was determined in their peripheral blood by quantitative PCR, and tryptase genotyping was performed by droplet digital PCR.
Results |
In all, 351 patients (93.9%) had normal levels of BST, and KIT p.D816V was detected in 8% of patients (28 of 351), predominantly in patients with the most severe Mueller grade IV anaphylaxis (18.2% [24 of 132] vs 1.8% in patients with lower grades [4 of 88 with grade III and 0 of 131 with other grades]; P < .001). In grade IV patients with a normal BST level, KIT p.D816V was associated with more severe symptoms, including a significantly higher frequency of loss of consciousness (58.3% [14 of 24] vs 34.3% [37 of 108]; P = .03) and absence of skin symptoms (41.7% [10 of 24] vs 15.7% [17 of 108]; P = .004). Among patients with a normal BST level, KIT p.D816V (OR = 10.25 [95% CI = 3.75-36.14]; P < .0001) was the major risk factor associated with severe HVA. Hereditary α-tryptasemia (HαT) due to increased germline copies of TPSAB1 encoding α-tryptase was the most common cause (65.2% [15 of 23]) of elevated BST level in patients with HVA, and together with KIT p.D816V, it accounted for 90% of BST level elevations (20 of 23) in patients with HVA.
Conclusion |
These results indicate that routine KIT p.D816V screening identifies clonal disease in high-risk patients with HVA who are regularly missed when BST level is used alone.
Le texte complet de cet article est disponible en PDF.Graphical abstract |
Key words : Anaphylaxis, venom, tryptase, mast cells, KIT p.D816V, hereditary α-tryptasemia
Abbreviations used : BST, HαT, HVA, MC, OR, SM, TPSAB1, VIT
Plan
| Supported in part by the Slovenian Research Agency (P3-0360) and by the Division of Intramural Research of the National Institute of Allergy and Infectious Diseases, National Institutes of Health. |
|
| Disclosure of potential conflict of interest: The authors declare that they have no relevant conflicts of interest. |
Vol 148 - N° 2
P. 621 - août 2021 Retour au numéro
Article précédent
- A population-based study on associations of stool microbiota with atopic diseases in school-age children
- Chen Hu, Evelien R. van Meel, Carolina Medina-Gomez, Robert Kraaij, Monica Barroso, Jessica Kiefte-de Jong, Djawad Radjabzadeh, Suzanne G.M.A. Pasmans, Nicolette W. de Jong, Johan C. de Jongste, Henriette A. Moll, Tamar Nijsten, Fernando Rivadeneira, Luba M. Pardo, Liesbeth Duijts
- Multidimensional study of the oral microbiome, metabolite, and immunologic environment in peanut allergy
- Hsi-en Ho, Yoojin Chun, Stephanie Jeong, Oranicha Jumreornvong, Scott H. Sicherer, Supinda Bunyavanich
Bienvenue sur EM-consulte, la référence des professionnels de santé.
L’accès au texte intégral de cet article nécessite un abonnement.
Déjà abonné à cette revue ?