Clonal mast cell disorders and hereditary α-tryptasemia as risk factors for anaphylaxis

Kačar, Mark (author), Rijavec, Matija (author), Šelb, Julij (author), Korošec, Peter (author)

The association between Hymenoptera venom-triggered anaphylaxis (HVA) and clonal mast cell-related disorders (cMCD) has been known for decades. However, recent breakthroughs in peripheral blood screening for KIT p.D816V missense variant have revealed the true extent of this clinical association whilst adding to our understanding of the underlying etiology. Thus, recent large studies highlighted the presence of KIT p.D816V among 18.2% and 23% of patients with severe Hymenoptera venom-triggered anaphylaxis. A significant proportion of those patients have normal serum basal tryptase (BST) levels, with no cutaneous findings such as urticaria pigmentosa or other systemic findings such as organomegaly that would have suggested the presence of cMCD. These findings of an increased prevalence suggest that the impact of cMCD on anaphylaxis could be clinically underestimated and that the leading question for clinicians could be changed from “how many patients with cMCD have anaphylaxis?” to “how many patients with anaphylaxis have cMCD?”. The discovery of hereditary α-tryptasemia (HαT)—a genetic trait caused by an increased copy number of the Tryptase Alpha/Beta 1 (TPSAB1) gene-, first described in 2016, is now known to underlie the majority of cases of elevated BST outside of cMCD and chronic kidney disease. HαT is the first common heritable genetic modifier of anaphylaxis described, and it is associated with increased risk for severe HVA (relative risk = 2.0), idiopathic anaphylaxis, and an increased prevalence of anaphylaxis in patients with cMCD, possibly due to the unique activity profile of α/β -tryptase heterotetramers that may potentiate immediate hypersensitivity reaction severity. Our narrative review aims to highlight recent research to have increased our understanding of cMCD and HαT, through recent lessons learned from studying their association with HVA. Additionally, we examined the studies of mast cell-related disorders in food and drug allergy in an effort to determine whether one should also consider cMCD and/or HαT in cases of severe anaphylaxis triggered by food or drugs.

• Language: English
• Keywords: anaphylaxis, venom, food, drugs, tryptase, mast cells, KIT p.D816V, hereditary α-tryptasemia, hypersensitivity, diagnosis, food hypersensitivity, drug hypersensitivity
• Work type: Article
• Typology: 1.02 - Review Article
• Organization: MF - Faculty of Medicine; BF - Biotechnical Faculty; FFA - Faculty of Pharmacy
• Publication status: Published
• Publication version: Version of Record
• Year: 2023
• Number of pages: Str. 392–404
• Numbering: Vol. 53, iss. 4
• PID: 20.500.12556/RUL-146023
• UDC: 616-097
• ISSN on article: 1365-2222
• DOI: 10.1111/cea.14264
• COBISS.SI-ID: 133239299
• Publication date in RUL: 18.05.2023

Record is a part of a journal

• Title: Clinical & experimental allergy
• Shortened title: Clin. exp. allergy
• Publisher: Wiley
• ISSN: 1365-2222
• COBISS.SI-ID: 515014681

Licences

• License: CC BY-NC-ND 4.0, Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International
• Link: http://creativecommons.org/licenses/by-nc-nd/4.0/
• Description: The most restrictive Creative Commons license. This only allows people to download and share the work for no commercial gain and for no other purposes.

Secondary language

• Language: Slovenian
• Keywords: triptaza, hereditarna α-triptazemija, živalski strupi, preobčutljivost, anafilaksija, diagnostika, mastociti, preobčutljivost za hrano, preobčutljivost za zdravila

Projects

• Funder: ARRS - Slovenian Research Agency