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Reference Guide
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Anti-vinculin IgA
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Anti-vinculin IgA

Anti-vinculin IgA is an autoantibody targeting vinculin, a protein that is important in cell adhesion and signaling, particularly within the gastrointestinal tract. 

This biomarker is a potential tool for better understanding autoimmune and gastrointestinal disorders, including diarrhea-predominant inflammatory bowel syndrome (IBS-D).

What is Vinculin?

Vinculin is a protein found inside cells that helps cells stick to their surroundings and to other cells. It connects the actin skeleton inside the cell to structures called integrins (which connect to the outside) in focal adhesions and cadherins (which connect to other cells) in adherens junctions. 

Vinculin helps cells stay connected, move, grow, and survive. It changes shape to bind to other proteins, which helps regulate how cells stick together, move, and react to forces. Vinculin also helps control how cells stick together in tissues, ensuring cell connections stay strong. 

Additionally, it plays a role in controlling apoptosis and in bacterial invasions. 

Because of these functions, vinculin is very important for normal development and the health of tissues. Problems with vinculin are linked to diseases like cancer and heart problems, as well as some systemic sclerosing and digestive disorders.

What is Anti-Vinculin IgA?

Anti-vinculin IgA is an autoantibody targeting vinculin, a key protein in the cytoskeleton of cells. 

In the gastrointestinal tract, IgA is a type of antibody that maintains intestinal homeostasis by protecting the gut from pathogens and regulating the interaction between the microbiota and host immune cells, ensuring a balanced immune response that avoids inflammation while supporting beneficial microbial communities.

Anti-Vinculin Antibodies in Disease

Anti-vinculin antibodies have been implicated in a variety of autoimmune and gastrointestinal conditions

These antibodies are most notably associated with diarrhea-predominant irritable bowel syndrome (IBS-D), where they may contribute to gastrointestinal symptoms through mechanisms like molecular mimicry with bacterial components, such as CdtB. 

Elevated levels of anti-vinculin antibodies are also found in systemic sclerosis (SSc), which correlate with increased gastrointestinal symptoms. This suggests a link between these antibodies and GI involvement in SSc. 

Furthermore, anti-vinculin antibodies and anti-CdtB antibodies serve as valuable biomarkers for distinguishing IBS-D from inflammatory bowel disease (IBD). They show higher levels in IBS-D compared to IBD and healthy controls.

Anti-Vinculin IgA and IBS-D

In particular, anti-vinculin IgA antibodies are notably elevated in IBS-D patients, with studies showing that their levels are significantly higher than those in patients with IBD. These antibodies have been proposed as potential biomarkers for IBS-D, offering a specificity of 90.9% and sensitivity of 52.2%.

This suggests that anti-vinculin IgA antibodies may play a role in the pathogenesis of IBS-D and could serve as a valuable tool in clinical diagnosis.

Who Should Get Anti-vinculin IgA Tested?

Anti-vinculin IgA testing is not yet routine but may be helpful in specific clinical scenarios. 

Clinicians should consider testing for anti-vinculin IgA in patients with gastrointestinal symptoms, such as abdominal pain, diarrhea, and bloating, which could indicate an underlying autoimmune or inflammatory disorder. 

Individuals who may benefit from differentiating IBS-D from IBD may also benefit from including anti-vinculin IgA as part of a comprehensive diagnostic process.

Test Procedure and Interpretation

The following section outlines the test procedure and interpretation: 

Testing Procedure and Preparation Requirements 

The standard procedure for testing anti-vinculin IgA involves drawing a blood sample. No fasting or special preparation is needed from the patient, though it's essential to consider their entire medical history when ordering the test. 

Medications or other factors that may interfere with test results should be noted.

Normal Reference Ranges 

Normal reference ranges for anti-vinculin IgA can vary depending on the laboratory. Generally, a negative or low level is considered typical, with elevated levels suggesting the presence of an autoimmune or inflammatory response. 

However, a positive result alone is not diagnostic and should be interpreted alongside other clinical and laboratory findings.

Clinical Implications of Elevated Levels 

Elevated levels of anti-vinculin IgA are most commonly associated with autoimmune and gastrointestinal issues such as scleroderma and/or IBS-D

However, it’s important to note that anti-vinculin IgA is still being researched, and its exact role in these conditions is not fully understood. 

A positive result should always be assessed in conjunction with the patient's symptoms and other diagnostic tests, as it may also be linked to other inflammatory or autoimmune disorders.

Clinical Implications of Decreased Levels 

Low or negative levels of anti-vinculin IgA generally suggest that this biomarker is not contributing to the patient’s symptoms. 

However, a negative result does not completely rule out the presence of conditions like IBS or other autoimmune diseases, especially if there is strong clinical suspicion. Clinicians should consider other diagnostic tests to explore alternative causes if needed.

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See References

Gutzeit, C., Magri, G., & Cerutti, A. (2014). Intestinal IgA production and its role in host-microbe interaction. Immunological reviews, 260(1), 76–85. https://doi.org/10.1111/imr.12189

Izard, T., & Brown, D. T. (2016). Mechanisms and Functions of Vinculin Interactions with Phospholipids at Cell Adhesion Sites. The Journal of biological chemistry, 291(6), 2548–2555. https://doi.org/10.1074/jbc.R115.686493

Morales, W., Parodi, G., Chuang, B., Weitsman, S., Mathur, R., Rezaie, A., Pimentel, M., & Leite, G. (2021). S525 Serum IgA Levels Are Significantly Decreased After Rifaximin Therapy in Patients With Diarrhea-Predominant Irritable Bowel Syndrome Whose Inflammatory State May Be Linked to Anti-Vinculin Antibodies. The American Journal of Gastroenterology, 116(1), S238–S238. https://doi.org/10.14309/01.ajg.0000774576.69047.ae

Morales, W., Rezaie, A., Barlow, G., & Pimentel, M. (2019). Second-Generation Biomarker Testing for Irritable Bowel Syndrome Using Plasma Anti-CdtB and Anti-Vinculin Levels. Digestive diseases and sciences, 64(11), 3115–3121. https://doi.org/10.1007/s10620-019-05684-6

Peng, X., Nelson, E. S., Maiers, J. L., & DeMali, K. A. (2011). New insights into vinculin function and regulation. International review of cell and molecular biology, 287, 191–231. https://doi.org/10.1016/B978-0-12-386043-9.00005-0

Rezaie, A., Park, S. C., Morales, W., Marsh, E., Lembo, A., Kim, J. H., Weitsman, S., Chua, K. S., Barlow, G. M., & Pimentel, M. (2017). Assessment of Anti-vinculin and Anti-cytolethal Distending Toxin B Antibodies in Subtypes of Irritable Bowel Syndrome. Digestive diseases and sciences, 62(6), 1480–1485. https://doi.org/10.1007/s10620-017-4585-z

Suliman, Y., Kafaja, S., Oh, S. J., Alemam, M., Bagnato, G., Abignano, G., Singh, R. R., Barlow, G., Liu, X., Valera, I., Morales, W., Rezaie, A., Pimentel, M., Del Galdo, F., & Furst, D. E. (2021). Anti-vinculin antibodies in scleroderma (SSc): a potential link between autoimmunity and gastrointestinal system involvement in two SSc cohorts. Clinical rheumatology, 40(6), 2277–2284. https://doi.org/10.1007/s10067-020-05479-5

Zhang, Y., Liao, J., & Fan, W. (2024). Role of autoantibodies in the pathophysiology of irritable bowel syndrome: a review. Frontiers in Physiology, 15. https://doi.org/10.3389/fphys.2024.1359003

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