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Reference Guide
Eosinophil Protein X
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Eosinophil Protein X
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Eosinophil Protein X

Eosinophil Protein X (EPX), also known as eosinophil-derived neurotoxin, is a granule protein released by eosinophils during inflammatory responses. As a biomarker, EPX has garnered significant attention for its potential to indicate various inflammatory and allergic conditions, especially within the gastrointestinal tract. 

Biochemical Characteristics of Eosinophil Protein X

Eosinophil Protein X, a crucial component of the immune response mediated by eosinophils, has a well-defined role in the body's defense mechanisms, particularly in conditions associated with allergies and infections. 

Structure and Biological Function of EPX  [7., 9., 10.] 

Eosinophil Protein X is a cationic protein found in the granules of eosinophils, a type of white blood cell predominantly involved in the immune response to parasites and in allergic reactions. 

The protein is characterized by its ability to damage parasitic and host tissues, which is crucial in containing infections but can also contribute to tissue damage in allergic diseases. 

Its molecular structure allows it to interact with various biological molecules and cells, mediating inflammatory responses and modulating immune signaling pathways.

Role of EPX in Inflammatory Processes  [3., 7.]

The involvement of EPX in inflammatory processes is marked by its dual role: it is protective in its ability to combat pathogens, yet it can be destructive, contributing to the pathology of allergic and autoimmune diseases. 

EPX levels are elevated in various inflammatory conditions, making it a potential marker for disease activity.

In the context of inflammation, EPX contributes to tissue remodeling and damage by promoting the release of cytokines and chemokines, which further recruit immune cells to the site of inflammation, amplifying the inflammatory response. 

Eosinophil Protein X as a Biomarker

Eosinophil Protein X has become a key biomarker for diagnosing and monitoring various diseases, particularly those characterized by eosinophilic activity. 

Applications of EPX in Diagnosing and Monitoring Diseases  [11.]

Eosinophil Protein X is particularly valuable in the diagnosis and management of diseases where eosinophils play a significant role, such as asthma, allergic rhinitis, and eosinophilic esophagitis. 

In these conditions, elevated EPX levels correlate with disease severity and activity, offering a tool for monitoring treatment efficacy and disease progression. 

Furthermore, in gastrointestinal disorders, the measurement of EPX in stool helps in the differential diagnosis of conditions like inflammatory bowel disease (IBD) and irritable bowel syndrome (IBS), aiding in the distinction between inflammatory and non-inflammatory processes.

Laboratory Testing for Eosinophil Protein X

Accurate measurement of Eosinophil Protein X is fundamental to its utility as a biomarker in clinical practice.

Testing for EPX, Sample Selection and Preparation

EPX levels can be measured in blood, serum, urine, and stool.  They are commonly tested in stool samples. 

EPX genetic testing is also available which may be performed in blood or via cheek swab.  

Special preparation may be required prior to obtaining a sample; it is important to consult with the ordering provider.  

Specifics of the Eosinophil Protein X Stool Test  [2., 13.]

The eosinophil protein x stool test is particularly valuable for gastrointestinal disorders, as it measures the level of EPX in stool, which reflects local eosinophil activity within the gut. 

This test is non-invasive and can be crucial for differentiating between IBS, which typically does not involve eosinophilic inflammation, and other inflammatory bowel diseases like Crohn’s disease or ulcerative colitis, where eosinophil levels may be elevated. 

The methodology involves collecting a stool sample from the patient, which is then analyzed using specialized assays to quantify EPX levels.

Interpretation of Results

Optimal Levels of EPX

It is important to consult with the ordering lab company to interpret results.  

For reference, one company reports the following optimal levels in stool testing for EPX:  [12.]

< 2.34 ug/g

Genetic testing should be interpreted by a healthcare professional, taking into account an individual’s personal and family health history.

Clinical Significance of Elevated EPX

Elevated levels of EPX in stool, for instance, might indicate an active eosinophilic inflammation, suggesting a diagnosis other than IBS.  In this case, IBD or an eosinophilic inflammatory response should be considered.

Clinical Significance of Low EPX

Generally, low EPX levels are not considered clinically relevant. 

However, in the setting of digestive upset, low levels of EPX could support a diagnosis of IBS, where inflammation is typically absent.  

It is important for clinicians to consider these results in the broader context of the patient’s symptoms and other diagnostic tests to make accurate and effective clinical decisions.

Eosinophil Protein X and Gastrointestinal Disorders

The role of Eosinophil Protein X in gastrointestinal health is increasingly recognized, particularly in its ability to distinguish between various types of gastrointestinal disorders. 

Role of EPX in Gastrointestinal Health  [1., 5., 13.]

Eosinophil Protein X is a marker of eosinophil activity, which is often elevated in gastrointestinal conditions characterized by inflammation, such as eosinophilic gastroenteritis and other forms of IBD. 

In these conditions, eosinophils infiltrate the gastrointestinal tract, and EPX released from these cells can be detected in stool samples.  The presence and level of EPX in the gastrointestinal tract provide insights into the inflammatory status and help clinicians assess the extent and activity of disease.

Correlation Between EPX Levels and Gastrointestinal Diseases  [2., 5., 13.]

Monitoring EPX levels can be particularly useful in the diagnosis and management of various gastrointestinal disorders. 

Elevated EPX levels in stool are indicative of eosinophilic involvement and can suggest a diagnosis of IBD or eosinophilic gastroenteritis, as opposed to IBS, which typically does not involve eosinophilic inflammation. 

The measurement of EPX thus helps in distinguishing between these conditions, which can often present with similar symptoms such as abdominal pain, diarrhea, and bloating.

Does a Low Eosinophil Protein X Signify IBS?  [6., 13.]

A key question in gastrointestinal diagnostics is whether low levels of EPX are indicative of IBS. 

Since IBS is primarily a functional disorder without the eosinophilic inflammation typical of IBD, low EPX levels can support a diagnosis of IBS.  However, clinicians must use caution, as low EPX levels alone are not sufficient to diagnose IBS. 

A comprehensive assessment including clinical evaluation, patient history, and other diagnostic tests are necessary to confirm IBS and rule out other inflammatory or functional gastrointestinal disorders.

Related Biomarkers and Their Tests

In addition to Eosinophil Protein X, several other biomarkers are crucial for the diagnosis and management of gastrointestinal and inflammatory diseases. 

Comparison with Other Eosinophil-Derived Biomarkers  [1., 11.]

While EPX is a valuable marker for eosinophil activity, it is not the only eosinophil-derived biomarker used in clinical practice. 

Other biomarkers such as eosinophil cationic protein (ECP) and major basic protein (MBP) also play roles in diagnosing and monitoring inflammatory conditions. 

These biomarkers can provide complementary information to EPX, as they may be elevated in different conditions or to varying extents.  

For instance, ECP is often used alongside EPX to assess the severity of eosinophilic esophagitis, providing a broader picture of eosinophil involvement and activity.

Integration of EPX Testing with Other Biomarkers for Comprehensive Diagnostics  [4., 13., 14.]

For a more accurate diagnosis of gastrointestinal disorders, EPX testing can be combined with other biomarkers.  

Calprotectin and lactoferrin are commonly measured to evaluate neutrophil activity, which is prominent in conditions like ulcerative colitis and Crohn's disease. 

Additionally, fecal occult blood tests are used to detect hidden blood in the stool, which can indicate gastrointestinal bleeding. 

Integrating these tests with EPX measurements allows clinicians to distinguish between different types of inflammatory bowel disease and other gastrointestinal conditions, ensuring that patients receive the most appropriate treatment.

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Eosinophil Protein X
Eosinophil Protein X (EPX) is a biomarker that measures the amount of eosinophils, or white blood cells, in your body. Eosinophils tend to accumulate in areas of inflammation, and release Eosinophil Protein X when they breakdown. Elevated levels of EPX can indicate an allergic reaction or infection and can be used to monitor inflammation in the lungs and other organs. EPX levels can be helpful with monitoring inflammatory bowel disease.
If Your Levels Are High
Symptoms of High Levels
If Your Levels are Low
Symptoms of Low Levels
See References

[1.] Abedin N, Seemann T, Kleinfeld S, Ruehrup J, Röseler S, Trautwein C, Streetz K, Sellge G. Fecal Eosinophil Cationic Protein Is a Diagnostic and Predictive Biomarker in Young Adults with Inflammatory Bowel Disease. J Clin Med. 2019 Nov 20;8(12):2025. doi: 10.3390/jcm8122025. PMID: 31756948; PMCID: PMC6947361.

[2.] Bischoff SC, Grabowsky J, Manns MP. Quantification of inflammatory mediators in stool samples of patients with inflammatory bowel disorders and controls. Dig Dis Sci. 1997 Feb;42(2):394-403. doi: 10.1023/a:1018886423475. PMID: 9052525.

[3.] Davoine F, Lacy P. Eosinophil cytokines, chemokines, and growth factors: emerging roles in immunity. Front Immunol. 2014 Nov 10;5:570. doi: 10.3389/fimmu.2014.00570. PMID: 25426119; PMCID: PMC4225839.

[4.] Emmanuel A, Landis D, Peucker M, Hungin AP. Faecal biomarker patterns in patients with symptoms of irritable bowel syndrome. Frontline Gastroenterol. 2016 Oct;7(4):275-282. doi: 10.1136/flgastro-2015-100651. Epub 2016 Mar 7. PMID: 27761231; PMCID: PMC5036220.

[5.] EnteroScan® - Intestinal Microbiome Tests | Diagnostiki Athinon’. Accessed May 20, 2024.

[6.] Goepp J, Fowler E, McBride T, Landis D. Frequency of abnormal fecal biomarkers in irritable bowel syndrome. Glob Adv Health Med. 2014 May;3(3):9-15. doi: 10.7453/gahmj.2013.099. PMID: 24891989; PMCID: PMC4030610.

[7.] Johansson O, Liang Y, Marcusson JA, Reimert CM. Eosinophil cationic protein- and eosinophil-derived neurotoxin/eosinophil protein X-immunoreactive eosinophils in prurigo nodularis. Arch Dermatol Res. 2000 Aug;292(8):371-8. doi: 10.1007/s004030000142. PMID: 10994770.

[8.] Katsanos AH, Kyriakidi K, Karassa FB, Politis D, Skamnelos A, Christodoulou DK, Katsanos KH. Biomarker Development in Chronic Inflammatory Diseases. Biomarkers for Endometriosis. 2017 Sep 23:41–75. doi: 10.1007/978-3-319-59856-7_3. PMCID: PMC7122305.

[9.] Katzinger J. Biomarkers for Stool Analysis. Textbook of Natural Medicine. Published online 2020:227-235.e5. doi:

[10.] Kim CK, Callaway Z, Pawankar R. Eosinophil granule proteins as a biomarker in managing asthma and allergies. Asia Pac Allergy. 2023 Jun;13(2):66-71. doi: 10.5415/apallergy.0000000000000104. Epub 2023 Jun 13. PMID: 37388815; PMCID: PMC10287111.

[11.] Pucci N, Lombardi E, Novembre E, Farina S, Bernardini R, Rossi E, Favilli T, Vierucci A. Urinary eosinophil protein X and serum eosinophil cationic protein in infants and young children with atopic dermatitis: correlation with disease activity. J Allergy Clin Immunol. 2000 Feb;105(2 Pt 1):353-7. doi: 10.1016/s0091-6749(00)90087-3. PMID: 10669858.

[12.] Rupa Health.  GI-MAP + Zonulin Sample Report.pdf. Google Docs. Accessed May 20, 2024.

[13.] Turkay C, Kasapoglu B. Noninvasive methods in evaluation of inflammatory bowel disease: where do we stand now? An update. Clinics (Sao Paulo). 2010 Feb;65(2):221-31. doi: 10.1590/S1807-59322010000200015. PMID: 20186307; PMCID: PMC2827710.

[14.] Vieira, A., Fang, C.B., Rolim, E.G. et al. Inflammatory bowel disease activity assessed by fecal calprotectin and lactoferrin: correlation with laboratory parameters, clinical, endoscopic and histological indexes. BMC Res Notes 2, 221 (2009).

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