Evaluation of Serum Zonulin Level and Intestinal Permeability in Patients with Chronic Spontaneous Urticaria and the Relationship Between Serum Zonulin Level and Disease Severity

Evaluation of Serum Zonulin Level and Intestinal Permeability in Patients with Chronic Spontaneous Urticaria and the Relationship Between Serum Zonulin Level and Disease Severity

Authors

  • Simge Ünal Dışkapı Yıldırım Beyazıt Hospital, Department of Dermatology and Venereology, Ankara, Turkey
  • Selda Pelin Kartal Dışkapı Yıldırım Beyazıt Hospital, Department of Dermatology and Venereology, Ankara, Turkey
  • Ahmet Ozsoy Dışkapı Yıldırım Beyazıt Hospital, Department of Clinic Biochemistry, Ankara, Turkey
  • Fevzi Nuri Aydın Dışkapı Yıldırım Beyazıt Hospital, Department of Clinic Biochemistry, Ankara, Turkey

Keywords:

Chronic Spontaneous Urticaria, Autoimmune Urticaria, anti-IgE, Intestinal Permeability, Zonulin

Abstract

Introduction: An emerging hypothesis suggests a potential link between enhanced intestinal permeability and the advancement of chronic spontaneous urticaria (CSU).

Objective: This study aimed to investigate the role of intestinal permeability in the etiopathogenesis of CSU by measuring serum zonulin levels, a marker of intestinal permeability, in both CSU patients and control subjects. Additionally, the study sought to explore the correlation between the severity of the illness and zonulin levels.

Methods: The study involved 61 patients with CSU and 59 healthy control individuals. For the CSU patients, comprehensive data was collected, encompassing various aspects: age at onset of the condition, duration of the most recent attack, presence of any comorbid conditions, dosage of antihistamines being used, the urticaria activity score, as well as detailed personal and family medical histories. Additionally, demographic information for these patients was also meticulously documented.

Result: The study revealed a statistically significant difference in zonulin levels between the CSU patient group and the control group, with a p-value of 0.000 indicating a highly significant disparity. Furthermore, among the CSU patients, those who were presented with angioedema exhibited considerably higher zonulin levels compared to those without angioedema. This variation in zonulin levels based on the presence of angioedema was also statistically significant, with a p-value of 0.023.

Conclusion:  The observed results suggest that increased intestinal permeability, as indicated by elevated zonulin levels, may play a crucial role in the pathophysiology of both CSU and angioedema. This association highlights the potential significance of intestinal permeability in the development and manifestation of these conditions.

References

Saini SS, Kaplan AP. Chronic Spontaneous Urticaria: The Devil’s Itch : Vol. 6. J Allergy Clin Immunol Pract. 2018;6(4):1097–1106. DOI: 10.1016/j.jaip.2018.04.013.

Gaig P, Olona M, Muñoz Lejarazu D, et al. Epidemiology of urticaria in Spain. J Investig Allergol Clin Immunol. 2004;14(3):214–220. PMID: 15552715.

Bracken SJ, Abraham S, MacLeod AS. Autoimmune theories of chronic spontaneous urticaria. Front Immunol. 2019;10(3):1–10. DOI: 10.3389/fimmu.2019.00627.

Hurtado-Avilés M, Martínez-Reculez M, Vargas-Camaño M, Castrejón-Vázquez M. Autoimmunity in chronic urticaria. A historical and current perspective. Rev Alerg Mex. 2022;69 :69-80. DOI: 10.29262/ram.v69iSupl1.1037.

Mu Q, Kirby J, Reilly CM, Luo XM. Leaky gut as a danger signal for autoimmune diseases. Front Immunol. 2017;8(5):1–10. DOI: 10.3389/fimmu.2017.00598.

Vancamelbeke M, Vermeire S. The intestinal barrier: a fundamental role in health and disease. Expert Rev Gastroenterol Hepatol. 2017;11(9):821–834. DOI:10.1080/17474124.2017.1343143.

Sekirov I, Russell SL, Caetano M Antunes L, Finlay BB. Gut microbiota in health and disease. Physiol Rev. 2010;90(3):859–904. DOI: 10.1152/physrev.00045.2009.

Sturgeon C, Fasano A. Zonulin, a regulator of epithelial and endothelial barrier functions, and its involvement in chronic inflammatory diseases Zonulin, a regulator of epithelial and endothelial barrier functions, and its involvement in chronic inflammatory diseases. Tissue Barriers. 2016 (1); 4(4). DOI: 10.1080/21688370.2016.1251384.

Fasano A. Physiological, pathological, and therapeutic implications of zonulin-mediated intestinal barrier modulation: Living life on the edge of the wall. Am J Pathol. 2008;173(5):1243–1252. DOI: 10.2353/ajpath.2008.080192.

Fasano A. Intestinal permeability and its regulation by zonulin: diagnostic and therapeutic implications. Clin Gastroenterol Hepatol. 2012 Oct 1;10(10):1096–1100. DOI: 10.1016/j.cgh.2012.08.012.

Asmar REL, Panigrahi P, Bamford P, et al. Host-dependent zonulin secretion causes the impairment of the small intestine barrier function after bacterial exposure. Gastroenterology. 2002;123(5):1607–1615. DOI: 10.1053/gast.2002.36578.

Fasano A. Zonulin and its regulation of intestinal barrier function: the biological door to inflammation, autoimmunity, and cancer. Physiol Rev. 2011;151–175. DOI: 10.1152/physrev.00003.2008.

Drago S, Asmar REL, Pierro MDI, et al. Gliadin, zonulin and gut permeability : Effects on celiac and non-celiac intestinal mucosa and intestinal cell lines. Scand J Gastroenterol. 2006;(3):408–419. DOI: 10.1080/00365520500235334.

Paterson BM, Lammers KM, Arrieta MC, Fasano A, Meddings JB. The safety, tolerance, pharmacokinetic and pharmacodynamic effects of single doses of AT-1001 in coeliac disease subjects: a proof of concept study. Aliment Pharmacol Ther. 2007;(6):757–766. DOI: 10.1111/j.1365-2036.2007.03413.x.

Heickman LKW, Deboer MD, Fasano A. Zonulin as a potential putative biomarker of risk for shared type 1 diabetes and celiac disease autoimmunity. Diabetes Metab Res Rev. 2020;(12):1–14. DOI: 10.1002/dmrr.3309.

Madsen KL, Malfair D, Gray D, Doyle JS, Jewell LD, Fedorak RN. Interleukin- 10 Gene-Deficient Mice Develop a Primary Intestinal Permeability Defect in Response to Enteric Microflora. Inflamm Bowel Dis. 1999;5(4):262–270. DOI: 10.1097/00054725-199911000-00004.

Peeters M, Geypens B, Claus D, et al. Clustering of Increased Small Intestinal Permeability in Families With Crohn’s Disease. Gastroenterology. 1997;113(3):802–807. DOI: 10.1016/s0016-5085(97)70174-4

Moulton V. Sex hormones in acquired immunity and autoimmune disease. Front Immunol. 2018;9:2279. DOI: 10.3389/fimmu.2018.02279.

Xiong Y, Piao W, Brinkman CC, et al. CD4 T cell sphingosine 1-phosphate receptor (S1PR) 1 and S1PR4 and endothelial S1PR2 regulate afferent lymphatic migration. Sci Immunol. 2019;1263(3). DOI: 10.1126/sciimmunol.aav1263.

Downloads

Published

2025-01-29

How to Cite

1.
Ünal S, Kartal SP, Ozsoy A, Aydın FN. Evaluation of Serum Zonulin Level and Intestinal Permeability in Patients with Chronic Spontaneous Urticaria and the Relationship Between Serum Zonulin Level and Disease Severity. Dermatol Pract Concept. 2025;15(1):4237. doi:10.5826/dpc.1501a4237

Share