D2.443 - Serum Zonulin Reflects Disease Activity and Psychiatric Burden in Hereditary Angioedema

Hereditary angioedema (HAE) is a rare inflammatory disease with recurrent angioedema attacks. It is also associated with a significant psychosocial burden. Zonulin regulates intestinal and blood–brain barrier permeability.  It has been implicated in a wide range of inflammatory and neuropsychiatric conditions. However, its role in HAE has not been previously investigated.

Twenty-eight patients with type 1 HAE due to C1 inhibitor deficiency and 30 age- and sex-matched healthy controls were included. Serum zonulin levels were measured using enzyme-linked immunosorbent assay. Patients were grouped according to monthly attack frequency (≥2 vs <2 attacks per month). Disease activity was further assessed by annual attack count. Psychiatric symptoms were evaluated using the Hospital Anxiety and Depression Scale (HADS).

Serum zonulin levels tended to be higher in patients with HAE than in controls (74.5 [38.3–138.7] ng/mL vs 44.9 [33.0–98.3] ng/mL; p = 0.06). Patients in the high-attack-frequency group had significantly higher zonulin levels than those in the low-attack-frequency group (p < 0.05) (Table 1). Zonulin levels showed a strong positive correlation with the number of attacks in the previous year (r = 0.82, p < 0.01). Receiver operating characteristic (ROC) analysis showed that serum zonulin discriminated the high-attack-frequency group (AUC = 0.977, p < 0.001), with a cutoff of 68.7 ng/mL (Figure 1). Higher serum zonulin levels were observed in patients with clinically significant anxiety or depressive symptoms, as assessed by the HADS (p = 0.039).

Serum zonulin levels were associated with both disease activity and psychiatric symptom burden in HAE. These findings suggest a link between barrier dysfunction and the multidimensional clinical burden of the disease. To our knowledge, this is the first pilot study to demonstrate that zonulin may represent a promising biomarker for disease monitoring in HAE.