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Celiac Disease and Its Pathogenesis


Celiac disease is caused by immune reactions to gluten; proteins available in cereal grains. It mainly targets the gastrointestinal tract organ; however, celiac disease is a vital consequence of cereal grain ingestion in majority of patients. The disease is associated with autoimmune disorders, gastrointestinal disorders and lymphomas of different varieties. Celia disease is often accompanied by whole-body problems that are related. The associated dysfunction and disease are expressions of delayed pattern of food allergy. Research on celiac disease enables us to form a model of delayed pattern of food allergy. Patients with celiac disease experience increased gastrointestinal permeability and demonstrate the whole body effects of food allergy, including brain dysfunction, arthritis, and inflammatory lung disease (Couston, 2008, p. 68). The following paper examines celiac disease mechanisms, serological testing of celiac disease, genetic predisposition and testing of celiac disease, and current research and development of celiac disease.

Celiac Disease Pathogenic Mechanisms

Celiac disease is a disease linked to HLA and thus, many pathogenesis revolves around its association with HLA class II genes (Heatly, 1994, p. 110). Other category II diseases such as diabetes and rheumatoid arthritis appear to be linked to the presence or absence of specific residues flanking the antigen binding groove, rather than a particular HLA type (Tomlinson, 2008, p. 129). As a permanent intolerant to gluten, celiac disease currently can be treated through adherence to diet free from gluten. According to Fassano (2008, p. 89), 70% of patients diagnosed with celiac disease and subjected to diet free from gluten reported symptom relief within two weeks (Tomlinson, 2008, p. 321). Normally, an inflammation cascade happens in the small intestinal mucosa when the patient with celiac acid eats gluten. This shows that the adaptive immune pathway can provide the major immune reaction (Fassano, 2003, p. 89).

Woolf (1998, p.522) states that, patients with celiac disease should consider complete diet revision, not just gluten exclusion to avoid problems downstream from their gastrointestinal. Diseases such as diabetes, thyroid, anaemia, migraine headaches, lung disease, epilepsy, autism, schizophrenia and others are linked to gluten intolerance (Woolf, 1998, p. 523). These linkages depict a tendency to immune diseases of hypersensitivity nature and the role of food antigens in causing systemic auto immune disease. Fassano (2003, p. 90) extorts Mulder and Tygart emphasis on the basic idea of pathogenesis of systemic disease downstream from a disordered gastrointestinal tract. They postulated that patients with celiac disease often possess circulating antibodies to food proteins. In addition, these patients have circulating immune complexes, indicating that unavailability of an intestinal IgA barrier can permit antigenic material absorption from the gut (Galagher, 2009, p. 100). Antibodies to some of the antigens might cross react with the host’s self components and might produce autoimmune disease indirectly. The striking association is that celiac disease predisposes patients to the eventual development of lymphoma. Evidence reveals that strict adherence to diet free from glut will reduce incidence of lymphoma in the long term (Braly, 2002, p. 77). Anti-gliadin antibodies are prevalent in immune complexes, linked with major systemic disease. A T cell-mediated or type IV reaction to gluten is likely to be a major cause of gut lesions and increased permeability to gluten and other food antigens lead to whole body consequences (Fassano, 2003, p. 121).

Prevalence of Celiac Disease

Celiac disease is prevalent in the general population. Cerf-Bensusa (2003, p. 109) estimates the prevalence to be 1 in 300. Evidence from current research suggests many more undiagnosed than diagnosed cases. The incidences may be as high as 5% of the general population (Cerf-Bensusa, 2003, p. 110). If one examines the symptomatic populations with gastrointestinal symptoms, food allergy symptoms and autoimmune disease, the prevalence might be much higher. Since strict diet free from glut is protective against complications of adult celiac disease, undiagnosed forms of celiac disease must be diagnosed and treated (Braly, 2002, p. 72).

Screening tests such as anti-gliadin and anti-endomysium antibody estimation can be applied in groups considered to be vulnerable of celiac disease. These groups may include; relatives of celiac patients, patients with irritable bowel syndrome, arthritis, iron deficiency anaemia, epilepsy and others (Walter, 2004, p. 222). The disadvantage with screening tests is that they can only identify individuals fit into a limited definition of any disease. Screening tests cannot assume individuals who would benefit from gluten exclusion (Butcher, 2004, p. 2003).

No test assumes gluten allergy. Kleinman (2008, p. 321) postulates that celiac disease may present in various forms. Their research indicated that the disease is more prevalent in women, and more severe and rapid. Their data suggested the need to look for celiac disease in patients with unexplained hypo chromic anaemia. All signs and symptoms were more prevalent in women than men except for asthenia. The most common finding was hypo chromic anaemia in women which was 40% higher in women than men (Butcher, 2004, p. 203). Dyspepsia was double as frequent in women as in men genital disorders and was reported by 44% of women and by no men. The commonest findings in men were recent weight loss. About 60% of men and women reported diarrhoea; among patients without diarrhoea, the frequency of hypo chromic anaemia varied between sexes, occurring in about 80% of women (Butcher, 2004, p. 213).

Diagnosis of Celiac Disease

Diagnosis of celiac disease is made clinically by a typical history and confirmed by small intestinal mucosal biopsy, which indicates atrophy of the absorptive surface. The diagnosis is based on finding the biopsy changes in the jejunum while the patient is on the gluten containing diet and on its disappearance once the gluten is excluded from the diet. In the typical scenario, jejunal biopsy brings out villous atrophy, inflammatory infiltrate of the lamina propria, and degeneration of the surface epithelium. As defined by the biopsy result, celiac disease may represent a specific endpoint for gluten reactions; one of many possible patterns of wheat allergy.

Data from research accumulated indicates the role of environmental factors. Celiac disease is a unique example of complex diseases where major environmental and genetic factors are known. Celiac disease develops following gluten ingestion in genetically susceptible individuals. Human Leukocyte Antigen in man on chromosome 6 plays the main role in establishing susceptibility to the disease. However, genes within Human Leukocyte Antigen complex accounts only for approximately 40% of the increased risk of disease in siblings, showing the contribution of other non-Human Leukocyte Antigen disease. Several attempts have been tried to detect other genes that predispose to celiac disease.

Morteau (2004, p. 158) cites Vogelsang et al report on the high frequency of lymphocytic gastritis in untreated celiac disease linked with elevated gastric permeability. Celiac disease is a general disorder of gastrointestinal tract associated with increased permeability. There is significant association of lymphocytic gastritis with celiac disease. Gastric permeability can be assessed by a sucrose test, and intestinal permeability measured by a lactulose test is increased in untreated celiac patients. This study by Vogelsang et al aimed to prospectively compare gastric and intestinal permeability with histological changes of the stomach and small bowel in patients with celiac disease (Morteau, 2004, p. 158). Urinary sucrose secretion was reduced after duodenal administration as opposed to oral administration and thus measured gastric permeability in celiac disease. Gastric permeability was elevated in 60% of celiac patients and correlated with antral intraepithelial lymphocyte counts (Morteau, 2004, p. 159). Intestinal permeability was also raised in 69% of the celiac disease patients. The objective was to examine permeability of gut to protein macromolecules and sugar probes and their possible association in celiac disease patients (Morteau, 2004, p. 160).

Researchers have also studied the permeability to human alpha-lactalbumin, beta-lacto globulin, mannitol, and lactulose on 46 occasions in 33 celiac disease patients in various phases of the disease. Absorption of lactalbumin was detected in 19 of 42 patients tested, more often in celiac disease patients with villous atrophy than in those with normal jejunal biopsy.

Serological Testing of Celiac disease

In patients with typical signs, symptoms and laboratory parameters the diagnosis of celiac disease is normally performed by doing a mucosal biopsy of the small bowel. Several serological tests have been developed using anti-reticulin antibodies, anti-gliadin antibodies (AGA), and smooth muscle endomysium antibodies (EMA), and more recently, anti-tissue transglutaminase antibodies (tTG) (Fassano, 2008, p. 90). Given that the pathogenesis of celiac disease appears to involve the interaction cereal grain gluten. Many of early reports focused on AGA as the primary serological test (Fassano, 2008, p. 121).

Most studies have examined both the IgG and the IgA subsets of AGA. The data from these studies demonstrate reasonable sensitivity but poor specificity for the IgG antibodies, predicting that it may be a general marker for increased gut permeability of any cause rather than an important factor in disease pathogenesis (Braly, 2002, p. 72). The IgA AGA has improved specificity at the expense of sensitivity. The development of the endomysial antibody test has renewed interest in serological diagnosis.

Serum immunological markers are preferred to screen for celiac disease with high sensitivity and specificity (Kleinman, 2008, p. p. 321). Screening tests utilized for other gastrointestinal mal-absorption disorders, for instance; glucose tolerance tests, fecal fat, serum carotene levels, permeability tests and others, are poorly specific for celiac disease and should not be used in place of serological markers (Walter, 2004, p. 222). It must be clearly understood that no screening test is perfect. The diagnosis of celiac disease remains a small intestinal biopsy and the patient’s response to diet free from glut, any patient with suggestive symptoms must have a bowel biopsy, even if the serology is negative (Rose, 2004, p. 221).

Frequently used serological tests include; anti-gliadin, anti-endomysium, and anti-tissue transglutaminase. Depending on the age of the patient, specificity, the population being examined, and the proficiency of the laboratory performing the test, sensitivity, and positive and negative predictive values can differ widely for each antibody (Marsh, 2008, p. 247). Conditions that may cause negative antibody situation include patients who make low levels or no immunoglobulin A (IgA), young children who may not produce autoimmune antibodies, an inexperienced lab, and testing while patients are already on diets free from glut. False positive tests can also be experienced in these antibody tests in normal individuals suffering from other gastrointestinal disorders and other autoimmune disorders. Serological tests applied to screen for celiac disease include; Anti-Gliadin Antibodies, Anti-Endomysium Antibodies, Transglutaminase Antibodies, and Genetic Testing (Braly, 78),

Anti-Gliadin Antibodies

Anti-gliadin serological tests were the first to be used in the 1970s to screen for celiac disease. It provided the initial step of recognizing celiac disease as an immune mediated disorder. Anti-gliadin antibodies IgA and IgG recognize small antigenic portions of gluten proteins referred to as gliadin. AGA IgG has good sensitivity, whereas AGA IgA has good specificity, and thus their combined application provided the first reliable screening test. However, normal individuals can have elevated AGA IgG, causing confusion among practitioners (Fassano, 2008, p.122). AGA IgG is important in screening individuals deficient in IgA, since other antibodies used for routine screening are mostly of the IgA category. Other conditions under which an elevated AGA IgG can be noticed include enteropathies where the gut is more permeable to gluten, such as parasitic infections, allergic gastroenteropathy, and autoimmune enteropathies (McDonald, 2010, p. 201). The advantage of AGA antibodies is that they are enzyme linked immunosorbent assay tests, and the results are independent of observer variability (Coulston, 2008, p. 67).

Anti-Endomysium Antibodies

Serological tests currently commercially available with the highest sensitivity and specificity are the anti-endomysium IgA antibody (EMA). It was invented in early 1980s and quickly gained use as part of a screening celiac panel by commercial labs in combination with AGA IgG and AGA IgA. False negative EMA can be witnessed in young children, those with IgA deficiency, and in the hands of inexperienced laboratory because of the subjective nature of the test. In addition, the substrate for this antibody was initially monkey oesophagus, making it expensive and unsuitable for screening large numbers of people. Human umbilical cord is now used as an alternative to monkey oesophagus in most commercial laboratories (Kleinman, 2008, p. 321).

Transglutaminase Antibodies

Tissue transglutaminase (TG) was described in 1997 as the auto antigen of EMA. The initial TG ELISA was guinea pig IgA, with a lower sensitivity and specificity than EMA (Cerf-Bensusa, 2003, p. 1). However, most commercial labs now use human recombinant tTG, which has enhanced sensitivity and specificity and correlates better with EMA IgA and intestinal biopsy results. The tTG IgA ELISA represents an improvement over the EMA IgA assay because it is less expensive, less consuming, and is not a subjective test, and can be done on a single drop of blood using a dot-blot technique Cerf-Bensusa, 2003, p. 6). This makes it an ideal test for mass serologic screenings. Positive tGA results may be seen in other autoimmune diseases, such as type 1 diabetes, autoimmune liver disease, autoimmune thyroid disease, and inflammatory bowel disease (Butcher, 2003, p. 145).

Genetic Predisposition and Testing of Celiac Disease

As a multi-factoral disorder, celiac disease is a combination of several factors together with environmental triggers necessary for its development. Celiac disease’s genetic predisposition is complex and involves the HLA-DQAI’05/DQBI’02 and DQBI”0301/DQB”0302 genes as major factors (Gallagher, 2009, p. 109). These genes are estimated to determine some 40% of hereditability of celiac disease. 60% of the other genetic susceptibility to celiac disease is shared between unknown some non-HLA genes, each of which is approximated to contribute only a small risk effect (McDonald, 2010, p. 201).

Celiac disease is the only autoimmune disease for which we understand the environmental trigger, gluten. It also has a strong genetic influence. According to McDonald (2010, p. 201) for instance, there can be up to a 20% disease frequency in the first degree. In addition, identical twins have a 75% concordant rate for celiac disease, whereas non identical twin does not differ from siblings. The risk of reoccurrence for siblings of celiac disease patients to develop the disease is estimated to be about 10%. The inheritance patterns in families suggest multiple involvements of genes in celiac disease (McDonald, 2010, p. 201).

Since 1974, genetic predisposition to celiac disease has been researched when the association with HLA molecules was discovered. HLA-DQ2 molecules present the main risk element for celiac disease and explain about 40% of heritability of the disease. Elaborate investigations on the patho-physiological role of HLA molecules in celiac disease have been carried out (McDonald, 2010, p. 201). Nevertheless, it has remained a challenge to characterize the remaining 60% of non-HLA heritability of celiac disease for the past 30 years and the subject of intensive genetic research (McDonald, 2010, p. 201). These show a genetic, in addition to environmental component.

Celiac disease is a complex genetic disorder, but the actual celiac genes have not yet been identified (Braly, 2002, p. 72). The strongest genetic determinant of risk for celiac disease appears to be the presence of certain HLA alleles. The presence of these HLA alleles, DQ2 and DQ8, is thought to account to up 40% of genetic load the familial risk for celiac disease (Heatly, 1994, p. 105). The HLA are markers that help identify cells

Current Research and Development of Celiac Disease

Current fundamental research and development relating to celiac disease focus on immunologic and genetic factors linked with sensitivity to gliadin. Recently published research has addressed specific questions, this includes: diagnosis, the role of the anti-endomysial antibody and the anti-tissue transglutaminase antibody for screening populations at risk, diagnosing symptomatic individuals and following the response to a diet free from gluten; treatment whether oats can e eaten safely by patients with celiac disease; prognosis, whether patients are in increased risk of malignancy and other autoimmune diseases and whether adherence to a diet free from glut reduces that risk (Gallagher, 2009, p. 100). The diagnosis and treatment of celiac disease are well designed in clinical practice.

Current research and development of celiac disease have led to convenient level of testing for celiac disease. It presents exciting innovation for the diagnosis of celiac disease that offers solutions to the current problems and testing errors. New directions have been initiated in celiac research (McDonald, 2010, p. 2010). These directions have created standards by which pathologists evaluate intestinal biopsy samples for celiac disease signs. Superior tests to the intestinal biopsy for locating celiac disease have been developed by Marsh and his colleagues (Marsh, 2008, p. 247). They have developed rectal challenge procedure that can be performed in the doctor’s office using plastic instruments, and clear, quantified results can be available in a matter of hours (Marsh, 2008, p. 248).

Rectal challenge is a procedure that involves taking a biopsy of the rectal mucosa. Then gluten flurry is placed into the biopsy site followed by a second biopsy from the same area four or more hours later. Analysis by computer of these tissue samples identifies immune reactions to gluten if they are present, thus leading to the diagnosis of celiac disease (Fassano, 2008, p. 121). This test differentiates those whose immune systems are sensitized to gluten from those who do not react to it. The discovery of tissue transglutaminase (tTG) as the antigen recognized by EMA has led to the development of assays to directly detect tTG antibody (Delegger, 2008, p.114).


In sum, celiac disease is characterized by loss of intestinal barrier functions, and evidence is now piling suggesting a role of increased intestinal permeability in the early stages of the disease pathogenesis. This new development subverts traditional theories underlying the development of autoimmunity, suggesting that celiac disease autoimmune process can be arrested if the interplay between the genes and environmental triggers is prevented by re-establishing intestinal barrier function (Rose, 2004, p. 222).


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