Many disease states can be identified by what are known as biochemical markers. These can be substances that are already found within the body, or can be introduced from an external source. Biochemical markers are often quite specific and are used to indicate either normal or diseased states within the human body. Celiac disease is no exception and itself too can be identified within the human body through the use of specific biochemical markers. However, it is only after looking at what celiac disease is, can the biochemical markers, be they primary (tTGA and EMA) or secondary (ARA and AGA), be understood fully.
Celiac disease is an intestinal disorder that is lifelong. It is a genetically inherited disorder that causes damage to this organ and alters the absorption of important nutrients and minerals. Gluten is the external cause of this damage and is a complex group of proteins found in wheat. The proteins that contain glutamine are those which are toxic to celiac patients. When a person with celiac disease ingests foods, medicines and even some vitamins containing gluten, the body responds with an autoimmune response which causes intestinal epithelial damage. This in turn releases the enzyme tissue transglutaminase (tTG) which cross-links gliadin - gliadin and gliadin - enzyme complexes which induces an autoimmune response lead by T cells derived in the gut REFERENCE 3 TEITZ. The body then acts to induce villous atrophy, hyperplasia of the crypts of Lieberkuhn and the increase of intraepithelial lymphocytes that act to cause further damage. This damage leads to small intestine damage and ultimately malabsorption. By exploring the pathological changes that cause celiac disease, and the bodyââ‚¬â„¢s natural responses; the importance of biochemical markers used in the detection and diagnosis of this disorder can be appreciated.
There are a variety of tests that are used in the diagnosis and monitoring of patients with celiac disease. IgA antibodies are mainly used for diagnosis of celiac disease. The two antibodies; anti tissue transglutaminase (tTGA) and anti endomysial (EMA) autoantibodies are used as first line diagnosis methods. Autoantibodies are produced by the patientsââ‚¬â„¢ immune system in response to the tissue transglutaminase enzyme. Mentioned earlier, it is this enzyme that ultimately induces the autoimmune T cell response that acts to cause damage of the villi in the small intestine. Blood tests are used to detect for tTGA and positive results highly suggest celiac disease. The endomysium is the connective cover that surrounds individual strands of skeletal muscle fibres and is used to help provide strength and support (http://www.aafp.org/afp/980301ap/pruessn.html). During the pathogenesis of celiac disease, autoantibodies to this endomysium are produced by the body and an immune response is initiated causing damage to the enzyme tTG (http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1379574/). Again, a blood test can be used to detect for these antibodies and can then be used to confirm an initial diagnosis. This test is quite useful as these autoantibodies are usually found in 96 - 100 % of patients with celiac disease (http://cm8ek7zy3d.scholar.serialssolutions.com/?sid=google&auinit=B&aulast=Van+Meensel&atitle=Diagnostic+accuracy+of+ten+second-generation+(human)+tissue+transglutaminase+antibody+assays+in+celiac+disease&id=doi:10.1373/clinchem.2004.035832&title=Clinical+chemistry+(Baltimore,+Md.)&volume=50&issue=11&date=2004&spage=2125&issn=0009-9147). The two biochemical markers, tTGA and EMA are vital in the diagnosis of celiac disease and are often usually conducted as first line detection.
As is the case with most disease states, often more than one biochemical marker is used to confirm a suspected diagnosis. Celiac disease is no exception and the autoantibodies; antireticulin (ARA) and antigliadin (AGA) are usually used secondary to tTGA and EMA and are used as confirmation to the initial diagnosis. Reticular fibres are composed of collagen and form connective tissue known as collagen that acts to support many soft tissues within the body (Burkitt et al., Wheater's Functional Histology, 3rd ed. (Churchill Livinstone), p. 62). During the pathogenesis, autoantibodies to reticulin are formed and a simple blood test can be conducted to test for these antibodies. These antibodies are found in approximately 60 % of patients with celiac disease and are an excellent supporting test to confirm for celiac disease (http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1412607/pdf/gut00629-0069.pdf). Although secondary, the ARA and EMA tests are quite useful in helping confirm and reiterate an initial diagnosis of celiac disease in suspected patients. As well as the tTGA test, an anti gliadin antibody (AGA) test can also be conducted. Gliadin, which is found in the complex network of glycoproteins that make up gluten, is cross-linked by tTG as mentioned earlier. It is the cross linking of this glycoprotein that induces an autoimmune response by the body to cause small intestine damage. As well as the autoantibodies produced by the body in response to tTG, so too are autoantibodies produced to gliadin (AGA). Again, blood tests are used to detect for the presence of AGA and a positive test is suggestive of celiac disease.
Biochemical markers are extremely important in helping to diagnose many diseases known to man. They are highly specific and have grown in importance as advances in medicine have progressed. Through the use of an array of biochemical markers, celiac disease can very confidently be diagnosed and monitored correctly.