D1.511 - Hereditary alpha-tryptasemia in chronic spontaneous urticaria: prevalence and clinical impact

Chronic spontaneous urticaria (CSU) is a disease characterized by mast cell activation. Hereditary α-tryptasemia (HαT) is a genetic trait defined by increased (>2) copy number of the TSA​B1 gene encoding α-tryptase, leading to elevated basal serum tryptase (BST). Although most carriers are asymptomatic, HαT is associated with severe insect venom anaphylaxis, idiopathic anaphylaxis, and mastocytosis. Thus, HαT may also modulate CSU phenotype and treatment requirements. The objective of this study is to assess the prevalence of HαT in CSU and its impact on clinical manifestations and therapy needs.

This retrospective and prospective single-center study included 185 CSU patients (130 female, 55 male) aged 14-99 years (median 42 years) from 2018 to 2023. Clinical data were collected via structured questionnaires on HαT-associated symptoms, anaphylaxis, atopy, drug hypersensitivity, comorbidities, and medication use, including treatment response. TPSAB1 copy number was measured by using droplet digital PCR. BST, total IgE, and anti-thyroperoxidase IgG antibodies were measured to define CSU endotypes, autoallergic (aaCSU) and autoimmune (aiCSU).

Of 185 CSU patients, only 6 (3.2%, 3F/3M) were HαT-positive. BST >8μg/L was significantly more frequent in HαT-positive patients (5/6 vs. 25/179; p=0.0004), consistent with HαT criteria. Clinical manifestations of CSU (pruritus 5/6 vs. 163/179, p=0.44; angioedema 4/6 vs. 98/179, p=0.69; wheals 6/6 vs. 160/179, p=1.00; flush 1/6 vs. 65/179, p=0.42; gastrointestinal symptoms 1/6 vs. 44/179, p=1.00) and CSU endotype distribution (aiCSU 0/8; aaCSU 5/116; p=1.0) did not differ significantly between HαT-positive and -negative patients. The proportion of patients with insufficiently controlled disease on fourfold-dose antihistamines requiring omalizumab was similar (5/6 vs. 112/179; p=0.42). Additional antihistamine use (2/5 vs. 77/112; p=0.33) and treatment response (4/5 vs. 77/112; p=1.00) were also comparable.

In this CSU cohort, the prevalence of HαT was 3.2% (6/185), which is within the range reported for the general population (approximately 5-8%). As expected, BST levels were significantly higher in HαT-positive patients, supporting the biological validity of HαT classification in our cohort. However, HαT status did not appear to influence CSU symptoms, endotype distribution, disease severity, or treatment response.