Tissue transglutaminase antibodies  | Anti-gliadin antibodies  |  Faecal calprotectin  |  Parietal cell antibodies  |  Helicobacter pylori antibodies 

Tissue transglutaminase antibodies

Promotion material

Performance characteristics
EliA Celikey (anti-tTG), Gliadin (pdf)

Antigens

Tissue transglutaminase belongs to a diverse family of calcium-dependent enzymes that catalyse cross-link formation between proteins. tTG is widely distributed in human organs and is found associated with fibres surrounding smooth muscle and endothelial cells in connective tissue. tTG plays a role in extracellular matrix assembly and tissue repair mechanisms. Wheat gliadins can act as a substrate for transglutaminase reactions.

Celikey uses human recombinant tissue transglutaminase, produced in eukaryotic cells (Baculovirus/Sf9 system). 

Disease association, antibody prevalence and specificity

Coeliac disease

• Clinical sensitivity: 96%
• Clinical specificity: 99%

Disease activity

Anti-tissue transglutaminase antibodies may have a place in monitoring dietary compliance, with titres being negative in more than 70% of treated patients with coeliac disease.

Information about the disease

When is the measurement recommended?

Suspicion of coeliac disease

Antibody isotype

IgA or IgG.

IgA deficiency is a special challenge in coeliac disease diagnostics. IgG anti-tTG antibodies are as characteristic of coeliac patients with IgA deficiency as are IgA class anti-tTG antibodies of patients with normal serum IgA values.

References

Mäki M, Collin P (1997)  |  Brusco G, Muzi P, Ciccocioppo R, et al. (1999)  |  Troncone R, Maurano F, Rossi M, et al. (1999)  |  Hansson T, Dahlbom I, Hall J, et al. (2000) 

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Anti-gliadin antibodies

Promotion material

Performance characteristics
EliA Celikey (anti-tTG), Gliadin (pdf)

Antigens

The term gluten comprises a whole series of proteins in the endosperm of the cereal genera of wheat, rye, barley and oats. They serve as a source of nitrogen for the germinating embryo, and are subclassified as albumins, globulins, glutelins and the coeliac disease-inducing gliadins. Gliadin (molecular weight 16-40 kDa) is a mixture of about 50 components. On the basis of electrophoretic mobility, gliadins can be divided into four major fractions: alpha-, beta-, gamma- and omega-gliadins. A-gliadin, a component of alpha-gliadin of known primary amino acid sequence, contains 32 glutamines and 15 prolines per 100 amino acid residues.

The Varelisa Gliadin Antibodies assays are coated with purified gliadin. 

Deamidated gliadin peptides

Recent research revealed that gliadin peptides crossing the mucosal border in CD patients are deamidated by tissue transglutaminase (tTG), which renders them much more immunogenic than unprocessed gliadin peptides. Deamidated gliadin peptides therefore represent more specific targets for the antibodies to gliadin that are produced in CD patients. 

The EliA Gliadin DP tests use the relevant synthetic deamidated gliadin peptides, which gives them excellent specificity. 

Disease association, antibody prevalence and specificity

• Coeliac disease = gluten-sensitive enteropathy (85-100% of children with coeliac disease during the active phase of the disease) 
• Other gastroenterological disorders (about 21% IgG, about 3% IgA)

Information about the disease

Disease activity

When gluten is withdrawn from the diet of the patient with coeliac disease, the IgA-AGA titre decreases rapidly to normal values while the IgG-AGA decreases slowly and may persist at low titre for months or years. During a diagnostic gluten challenge, both IgG and IgA-AGA usually reach pathological values after some weeks or months of gluten ingestion. 

When is the measurement recommended?

• Suspicion of coeliac disease 
• Differential diagnosis of childhood and adult forms of coeliac disease 
• Follow-up of gluten-free diets 
• Suspicion of dermatitis herpetiformis

Antibody isotypes

IgA and IgG. IgA is more specific but less sensitive, while IgG is sensitive but less specific. The determination of both isotypes is therefore usually recommended. Patients with selective IgA deficiency can only be detected by screening with an IgG-class antibody.

References

Mäki M, Collin P (1997)  |  Catassi C (1996)  |  Unsworth DJ (2000)  |  Troncone R, Ferguson A (1991)   

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Faecal calprotectin NEW!

Promotion material

Performance characteristics
EliA Calprotectin folder (pdf)
EliA Calprotectin detailer (pdf)

Stool extraction
Stool extraction (pdf)

Calprotectin

In contrast to other EliA tests, EliA Calprotectin is not an antibody test but measures the amount of the protein calprotectin in the patient’s stool.
Inflammation is characterized by the increased activity of immune cells (e.g. neutrophil granulocytes) that release pathogen-attacking substances such as calprotectin.
In intestinal inflammation, the barrier function of the intestinal wall is lost and neutrophil granulocytes migrate through the wall into the intestinal lumen. This leads to an elevated calprotectin level in the stool. The level of faecal calprotectin correlates directly with the number of neutrophil granulocytes in the intestinal lumen. As such it is specifically elevated in inflammatory bowel diseases (IBD) such as Crohn's disease and ulcerative colitis. The level of calprotectin in faeces is approximately 6 times higher than in serum.

The EliA Calprotectin wells are coated with a monoclonal calprotectin antibody that binds calprotectin present in the patient’s stool sample.

Sensitivity and specificity

Faecal calprotectin is a very sensitive and specific marker for inflammation in the intestinal tract. As a first-line test, a negative result can rule out an inflammatory process while a positive result may prioritize endoscopy in the diagnostic path. Almost 98% of patients with inflammatory bowel diseases such as Crohn’s disease or ulcerative colitis have an increased level of faecal calprotectin. The specificity of the test is almost 90% (internal study).

Disease activity

Faecal calprotectin is an efficient marker for therapeutic effectiveness and mucosal healing because its level correlates well with endoscopic and histological findings in inflammatory bowel diseases. In recent studies it was shown that the faecal calprotectin level can predict relapse in Crohn's disease and ulcerative colitis.

When is the measurement recommended?

• Suspicion of inflammatory bowel disease (IBD) such as Crohn’s disease or ulcerative colitis.
• Differentiation from irritable bowel syndrome and other functional bowel disorders.
• Monitoring of IBD.

References

Vermeire S et al. (2006)  |  Konikoff MR, Denson LA (2006)  |  Gisbert JP, McNicholl AG (2009)  |  Sutherland AD et al. (2008)  |  Gaya DR, Mackenzie JF (2002)  |  Aadland E, Fagerhol MK (2002)     

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Parietal cell antibodies

Antigens

Circulating autoantibodies to gastric parietal cells were first detected in patients with pernicious anaemia. Subsequent biochemical and molecular cloning studies identified the autoantigens as the alpha- and beta-subunits of the gastric H+/K+-ATPase (92 and 60-90 kDa, respectively). The membrane-bound gastric H+/K+-ATPase is a proton pump responsible for the acidification of the stomach lumen. It is localized to specialized intracellular and apical membranes of parietal cells of the gastric mucosa.

The Varelisa Parietal Cell Antibodies assay uses purified H+/K+-ATPase. 

Antibody specificity and prevalence

• Pernicious anaemia (55-90%) 
• Chronic atrophic gastritis type A 
• Autoimmune endocrine disorders such as thyrotoxicosis, Hashimoto's thyroiditis and insulin-dependent diabetes mellitus (20-30 %) – in these cases there is a high risk of type-A gastric lesion 
• Healthy individuals (2-5%), increasing with age

Information about pernicious anaemia

Disease activity

A correlation between autoantibody titre and the severity of gastric atrophy is supported by one study but not by another. Treatment with corticoid drugs results in the regeneration of gastric parietal cells. However, the activities of parietal cell autoantibodies showed no correlative change.

When is the measurement recommended?

• Suspicion of pernicious anaemia 
• Differentiation of type-A atrophic gastritis from the other forms of nonspecific histological gastritis (type-B, Helicobacter pylori-associated gastritis, type-AB, and reflux gastritis following surgery)

Antibody isotype

IgG

References

Gleeson PA, van Driel IR, Toh B-H (1996)  |  Toh BH, Sentry JW, Alderuccio F (2000)  |  Klaasen CH, De Pont JJ (1994)

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Helicobacter Pylori Antibodies

Antigens

The Varelisa Parietal Cell Antibodies assay uses purified H. pylori surface antigens and recombinant 120 kDa antigen. 

Antibody specificity and prevalence

The organism known as Helicobacter pylori was first discovered and reported in 1983 by Warren and Marshall. They reported a new Gram-negative spiral bacterium found in gastric mucosa and associated with active, chronic gastritis. While it is assumed that H. pylori causes chronic gastritis, is implicated as a major cause of gastric and duodenal ulcer disease and is recognized as a class I carcinogen for gastric cancer.

Studies have shown that H. pylori infection is ubiquitous, with approximately 50% of the world's population estimated to be infected. The prevalence is higher in developing countries (up to 79%) than in developed states.

Several invasive and non-invasive techniques have been described for diagnosing H. pylori infection. Of the invasive tests available, histology and the rapid urease tests are the most commonly used. Although these methods have very high positive predictive values, they require biopsies to be taken from the upper gastrointestinal tract. Commonly used non-invasive tests are the urea breath test, which requires the ingestion of isotopically labelled urea, and serological methods that determine serum antibodies to H. pylori.

When is the measurement recommended?

• Chronic gastritis
• Duodenal ulcer
• Suspicion of infection with H. pylori

Antibody isotype

IgG

References

Warren JR, Marshall BJ.  |  Asaka M et al.  |  Azuma T et al.

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