Intended Use
This ELISA is intended for the quantitative determination of zonulin in stool.
Contents of Kit
1. MTP: Microtiter plate, coated; 12 x 8 wells
2. WASHBUF: Wash buffer concentrate, 10x; 2 x 100 mL
3. DIL: Dilution buffer concentrate, 2.5x; 2 x 100 mL
4. TRACER: Tracer, biotinylated zonulin, concentrate, 100x; 1 x 300 μL
5. CONJ: Conjugate, peroxidase-labeled streptavidin, concentrate, 100x; 1 x 200 μL
6. STD: Standards (lyophilized); 4 x 5 vials
7. CTRL1: Control (lyophilized); 4 x 1 vial
8. CTRL2: Control (lyophilized); 4 x 1 vial
9. SUB TMB: substrate (Tetramethylbenzidine), ready to use; 1 x 15 mL
10. STOP: ELISA stop solution, ready to use; 1 x 15 mL
For reorders of single components, use the catalogue number followed by the label as product number.
Detection Range
0.25-16 ng/ml
Sensitivity
Limit of blank, LoB 0.118ng/ml
Limit of detection, LoD 0.184ng/ml
Limit of quantitation, LoQ 0.188ng/ml
General Description
Zonulin is a novel human protein analogue to the zonula occludens toxin derived from Vibrio cholerae which participates in tight junctions between cells of the wall of the digestive tract. Zonulin binds to a specific receptor on the surface of intestinal epithelia and triggers a cascade of biochemical events which induces tight junction disassembly and a subsequent permeability increase of the intestinal epithelia, allowing some substances to pass through and activate immune reactions.
Fasano and his co-workers found that the zonulin-zonulin-receptor-system is more activated in celiac disease and type 1 diabetes mellitus patients. Patients with active celiac disease showed higher levels of zonulin and anti-zonulin antibodies compared to non-celiac patients and patients in remission, who were on a gluten-free diet. Concerning the autoimmune type 1 diabetes, in experiments with rats it could be demonstrated that elevated zonulin levels as well as increased intestinal permeability precede a type 1 diabetes disease. Conversely, type 1 diabetes could be prevented by inhibition of zonulin in animal experiments.
In addition, it was reported that many people who suffer from celiac disease also suffer from other autoimmune disorders. It is suggested that increased levels of zonulin are a contributing factor to the development of celiac disease and other autoimmune disorders such as insulin dependent diabetes, multiple sclerosis and rheumatoid arthritis.
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Zonulin, a novel protein discovered in 2000, acts similarly to Zonula occludens toxin (Zot) secreted by Vibrio cholerae and regulates the permeability of intercellular tight junctions, which is a dynamic structure involved in the vectorial transport of water and electrolytes across the intestinal epithelium. It is the only physiological regulator of tight intercellular junction found so far. It has been found to be involved in intestinal innate immunity and up-regulated in several autoimmune diseases including celiac disease (CD) and type 1 diabetes (T1D).
Zonulin is pre-haptoglobin (Hp)-2, the pro-protein of Hp2 before enzymatic cleavage into its mature form. Since each individual has 2 alleles for haptoglobin, there are 3 possible human genotypes (Hp1–1, Hp1–2, Hp2–2). Those who possess the HP2 allele (Hp1–2 or Hp2–2) produce active zonulin (pre-Hp2) whereas those with the Hp1–1 genotype do not have detectable zonulin. The frequency of each binding bead protein phenotype varies worldwide depending on the study population. In addition, the Hp2 genotype (high zonulin-producers) occurs more frequently in patients with celiac disease and inflammatory bowel disease than in the general population. The researchers also found that the prevalence of the human Hp2-2 genotype is also increased in those with morbidity due to inflammatory diseases, particularly in cardiovascular and renal morbidity in patients with T1D. In addition, there is evidence that Hp2 has lower antioxidant activity compared to Hp1, leading to the hypothesis that high zonulin-producing genotypes carry some degree of genetic risk for inflammatory diseases, which may be related to pre-Hp2, zonulin production, and its effect on the intestinal barrier.
Figure 1. The structure of pre-haptoglobin 1 (pre-Hp1) and pre-haptoglobin 2 (pre-Hp2) and their mature proteins
(Source: Wood Heickman LK, et al. 2020)
Creative Diagnostics provides human zonulin ELISA kits suitable for fecal samples to help you perform quantitative zonulin assays.
Alternative Names
Human pre-haptoglobin 2 ELISA Kit
Human pre-Hp2 ELISA Kit
References
1. Wood Heickman LK, et al. Zonulin as a potential putative biomarker of risk for shared type 1 diabetes and celiac disease autoimmunity. Diabetes Metab Res Rev. 2020 Jul;36(5):e3309.
2.Sturgeon C, et al. Zonulin, a regulator of epithelial and endothelial barrier functions, and its involvement in chronic inflammatory diseases. Tissue Barriers. 2016 Oct 21;4(4):e1251384.
Zonulin as a potential putative biomarker of risk for shared type 1 diabetes and celiac disease autoimmunity.
Diabetes Metab Res Rev
Authors: Wood Heickman LK, DeBoer MD, Fasano A.
Abstract
The incidence of type 1 diabetes (T1D) is increasing annually, in addition to other childhood-onset autoimmune diseases. This review is inspired by recent strides in research defining the pathophysiology of autoimmunity in celiac disease, a disease that has significant genetic overlap with T1D. Population genetic studies have demonstrated an increased proportion of newly diagnosed young children with T1D also have a higher genetic risk of celiac disease, suggesting that shared environmental risk factors are driving the incidence of both diseases. The small intestine barrier forms a tightly regulated interface of the immune system with the outside world and largely controls the mucosal immune response to non-self-antigens, dictating the balance between tolerance and immune response. Zonulin is the only known physiological modulator of the intercellular tight junctions, important in antigen trafficking, and therefore, is a key player in regulation of the mucosal immune response. While usually tightly controlled, when the zonulin pathway is dysregulated by changes in microbiome composition and function, antigen trafficking control is lost, leading to loss of mucosal tolerance in genetically susceptible individuals. The tenant of this hypothesis is that loss of tolerance would not occur if the zonulin-dependent intestinal barrier function is restored, thereby preventing the influence of environmental triggers in individuals genetically susceptible to autoimmunity. This review outlines the current research and a structured hypothesis on how a dysregulated small intestinal epithelial barrier, a "leaky gut," may be important in the pathogenesis of autoimmunity in certain individuals at risk of both T1D and celiac disease
Zonulin, a regulator of epithelial and endothelial barrier functions, and its involvement in chronic inflammatory diseases
Tissue Barriers
Authors: Sturgeon C, Fasano A.
Abstract
Beside digesting nutrients and absorbing solutes and electrolytes, the intestinal epithelium with its barrier function is in charge of a tightly controlled antigen trafficking from the intestinal lumen to the submucosa. This trafficking dictates the delicate balance between tolerance and immune response causing inflammation. Loss of barrier function secondary to upregulation of zonulin, the only known physiological modulator of intercellular tight junctions, leads to uncontrolled influx of dietary and microbial antigens. Additional insights on zonulin mechanism of action and the recent appreciation of the role that altered intestinal permeability can play in the development and progression of chronic inflammatory disorders has increased interest of both basic scientists and clinicians on the potential role of zonulin in the pathogenesis of these diseases. This review focuses on the recent research implicating zonulin as a master regulator of intestinal permeability linked to the development of several chronic inflammatory disorders.
COA
Certificate of Analysis