Evidence mapPaperPMID 41742205Full record

ArticleOrphanet journal of rare diseases2026

Elevated serum zonulin is associated with high attack frequency in hereditary angioedema: providing insight into the gut-angioedema axis.

Ragıp Fatih Kural, Kasım Okan, Onurcan Yildirim, Elif Azarsiz, Serpil Akten, Reyhan Gumusburun, Ceyda Tunakan Dalgic, Nihal Mete Gokmen

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Article in Orphanet journal of rare diseases, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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1 · What the graph read from it

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4 · The record

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5 · Who and what money

Authors and funding

8 authors.

Ragıp Fatih KuralDivision of Allergy and Immunology, Department of Internal Medicine, Ege University Faculty of Medicine, İzmir, Türkiye.
Kasım OkanDivision of Allergy and Immunology, Department of Internal Medicine, Ege University Faculty of Medicine, İzmir, Türkiye.
Onurcan YildirimDivision of Allergy and Immunology, Department of Internal Medicine, Ege University Faculty of Medicine, İzmir, Türkiye.
Elif AzarsizDepartment of Medical Biochemistry, Ege University Faculty of Medicine, İzmir, Türkiye.
Serpil AktenDivision of Allergy and Immunology, Department of Internal Medicine, Ege University Faculty of Medicine, İzmir, Türkiye.
Reyhan GumusburunDivision of Allergy and Immunology, Department of Internal Medicine, Ege University Faculty of Medicine, İzmir, Türkiye.
Ceyda Tunakan DalgicDivision of Allergy and Immunology, Department of Internal Medicine, Ege University Faculty of Medicine, İzmir, Türkiye.
Nihal Mete GokmenDivision of Allergy and Immunology, Department of Internal Medicine, Ege University Faculty of Medicine, İzmir, Türkiye. enihalmete@yahoo.com.tr.ORCID http://orcid.org/0000-0002-2450-5439

Funding

National Rare Diseases Association (Türkiye) National Rare Diseases Association (Türkiye)
6 · The paper itself

Abstract

backgroundZonulin is a key regulator of epithelial barrier permeability and has been implicated in barrier dysfunction across various inflammatory conditions. To elucidate the potential role of intestinal permeability in HAE, this study investigated serum zonulin levels and evaluated their association with disease activity and psychiatric status. PATIENTS AND

methodsThe study included 28 patients with HAE type 1 (HAE-C1INH) and 30 age- and sex-matched healthy controls. Serum zonulin levels were measured by ELISA. Patients were stratified according to attack frequency (high: ≥2 vs. low: <2 attacks/month). Psychiatric status was assessed using the Hospital Anxiety and Depression Scale (HADS). Multivariable linear regression analysis was performed to evaluate the association between zonulin levels and attack frequency after adjustment for body mass index (BMI).

resultsOverall serum zonulin levels did not differ significantly between patients with HAE and healthy controls (p = 0.06). However, stratified analyses revealed that patients with high attack frequency exhibited significantly higher zonulin levels compared with both low-attack-frequency patients and controls (p < 0.01), whereas zonulin levels in the low-attack-frequency group were comparable to controls. In multivariable analysis, attack frequency remained independently associated with serum zonulin levels after adjustment for BMI. Although zonulin levels were higher among patients with clinically significant anxiety and/or depressive symptoms based on HADS, this association was weaker than that observed for attack frequency.

conclusionsThis pilot study provides preliminary evidence that elevated serum zonulin levels in HAE are associated with higher attack burden, rather than representing a uniform feature of the disease. These findings suggest that zonulin elevation reflects inflammatory activity independent of psychiatric symptom burden and position intestinal barrier integrity as a relevant mechanistic component within the proposed Gut-Angioedema Axis. Future prospective studies are warranted to validate these findings.

trial registrationNot applicable.

Indexed as

Cholera ToxinAdultCase-Control StudiesFemaleHaptoglobinsHumansIntestinal Barrier FunctionMaleMiddle AgedProtein PrecursorsCholera ToxinHaptoglobinsProtein PrecursorszonulinBiomarkerHereditary angioedemaIntestinal permeabilityPsychological burdenZonulin

Identifiers

PMID41742205
PMCPMC13041075

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.