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The importance of anti-transglutaminase IgA antibody detection in the diagnosis of celiac disease - case report of an inappropriate diagnostic approach.

Szymańska E, Szymańska S, Pawłowska J, Orłowska E, Konopka E, Cukrowska B - Prz Gastroenterol (2015)

View Article: PubMed Central - PubMed

Affiliation: The Children's Memorial Heath Institute, Warsaw, Poland.

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Celiac disease (CD) is a chronic autoimmune intestinal disease caused by intolerance to gluten... Such a diagnostic approach concerns patients who present with clinical CD symptoms and strictly fulfil the following criteria: 1) TGA-IgA are highly elevated (greater than 10 times the upper limit of normal values), 2) antibody positivity is verified by IgA anti-endomysial antibodies (EMA) from a blood sample taken separately from the initial test, 3) positive HLA-DQ2 or/and -DQ8 haplotypes are confirmed by genetic tests, and 4) the response to a gluten-free diet is observed... Increased IEL number is actually considered the most important histological feature indicative of CD because atrophy of small intestinal mucosa with an absence of normal intestinal villi may occur in many entities such as microvillus inclusion disease, autoimmune enteropathy, intolerance to food (e.g. cow's milk, eggs, or soya), and eosinophilic gastroenteritis... Negative stool cultures excluded gastrointestinal infections... Bearing in mind the above laboratory results, colonoscopy without gastroduodenoscopy was performed... At first, complete serological testing according to the ESPGHAN guidelines for diagnosis of CD was performed (TGA-IgA, total IgA, and EMA, which were previously negative)... Total IgA within normal limits, increased TGA-IgA (22 U/ml; normal range up to 10 U/ml), and slightly positive EMA in titre 1: 5, but negative in titre 1: 10, were found... Currently, EMA should be used only in selected cases, when the diagnosis of CD can be made without small intestine biopsy, i.e. in children and adolescents with symptoms suggestive of CD and with high TGA-IgA concentration > 10 times the upper normal limit... Thus, in patients with positive specific TGA-IgA antibodies and a lack of specific histological changes, a follow up biopsy should be done... Although in our patient HLA examination was not performed, in such atypical patients, molecular testing could be done due to its great negative predictive value (about 99% of patients have HLA-DQ2 and/or HLA-DQ8 haplotype)... Interestingly, the specimens taken during the second colonoscopy presented normal histological features, whereas chronic inflammation with polymorphic and eosinophilic infiltrates had been found in the large intestine when colonoscopy had been done at the regional hospital... However, the hypothesis that CD onset was initiated by inflammatory/allergic reactions to antigens other than gluten cannot be excluded... Although gluten is the main external trigger of CD, its intake does not fully explain the pathogenesis of the disease... The disease can develop at any time during life, irrespective of diet – whether including gluten proteins or not... Lahdenperä et al. have proven that a gluten-free diet, which improves mucosal lesions, does not correct the increased activation of pro-inflammatory mediators of CD.

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Related in: MedlinePlus

A – The biopsy specimen from the duodenum taken during the first hospitalisation in the Children's Memorial Heath Institute. Duodenal villi are normally formed with the absence of inflammation, the number of IELs is significantly increased, varying from 30 up to 50 lymphocytes per 100 enterocytes. Original magnification 20×. B – Increased number of IEL stained with anti-CD3 antibody (red colour) are visible in the duodenal specimen. Original magnification 40×
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Figure 0001: A – The biopsy specimen from the duodenum taken during the first hospitalisation in the Children's Memorial Heath Institute. Duodenal villi are normally formed with the absence of inflammation, the number of IELs is significantly increased, varying from 30 up to 50 lymphocytes per 100 enterocytes. Original magnification 20×. B – Increased number of IEL stained with anti-CD3 antibody (red colour) are visible in the duodenal specimen. Original magnification 40×

Mentions: A 14-year-old girl was admitted to the regional hospital due to chronic diarrhoea persisting for 5 weeks. The physical examination at admission revealed no abnormalities apart from poorly developed subcutaneous tissue – both the body mass and the height at the 3rd percentile. The laboratory tests showed leucocytosis and eosinophilia with increased IgE level. To exclude CD, EMAs were done, and they were negative. The ultrasound imaging showed no abnormalities. Negative stool cultures excluded gastrointestinal infections. Bearing in mind the above laboratory results, colonoscopy without gastroduodenoscopy was performed. Histological examination showed chronic inflammation in the large intestine with polymorphic infiltrates, in which eosinophils dominated. The girl, with an initial discharge diagnosis of ulcerative colitis (UC), was given mesalazine and she was referred to the Department of Gastroenterology, Hepatology, and Feeding Disorders of the Children's Memorial Health Institute (CMHI) in Warsaw to extend the diagnostic workup. At first, complete serological testing according to the ESPGHAN guidelines for diagnosis of CD was performed (TGA-IgA, total IgA, and EMA, which were previously negative). Total IgA within normal limits, increased TGA-IgA (22 U/ml; normal range up to 10 U/ml), and slightly positive EMA in titre 1: 5, but negative in titre 1: 10, were found. Both gastroduodenoscopy and colonoscopy were performed. Histological examination revealed pathologic changes restricted to the duodenum. Although duodenal villi were normally formed with the absence of inflammation (Figure 1 A), the number of IEL was increased, varying from 30 up to 50 lymphocytes per 100 enterocytes (Figure 1 B). Thus, histological changes were classified as grade 1 according to the modified Marsh-Oberhuber classification. There were no abnormalities within the large intestine; therefore, the diagnosis of UC was excluded and the treatment with mesalazine was discontinued. The ordinary gluten-full diet was ordered, and 6 months later the girl was re-admitted to the CMHI in order to perform control gastroduodenoscopy. This time histopathological features were explicitly indicative of CD and classified as grade 3 C according to Marsh-Oberhuber classification. Either in duodenal bulb or in other parts of the duodenum flattened villi with significantly increased number of IEL (50 lymphocytes per 100 enterocytes) and moderate polymorphic infiltrates in the lamina propria were observed (Figure 2). Repeated serological tests showed increased level of TGA-IgA (16 U/ml) and negative EMA in titre 1: 5. Finally, CD was recognised. A gluten-free diet and a follow-up visit at the outpatient gastroenterology clinic were ordered. At present, the girl is doing well, the diarrhoea has stopped, and her nutritional status has improved.


The importance of anti-transglutaminase IgA antibody detection in the diagnosis of celiac disease - case report of an inappropriate diagnostic approach.

Szymańska E, Szymańska S, Pawłowska J, Orłowska E, Konopka E, Cukrowska B - Prz Gastroenterol (2015)

A – The biopsy specimen from the duodenum taken during the first hospitalisation in the Children's Memorial Heath Institute. Duodenal villi are normally formed with the absence of inflammation, the number of IELs is significantly increased, varying from 30 up to 50 lymphocytes per 100 enterocytes. Original magnification 20×. B – Increased number of IEL stained with anti-CD3 antibody (red colour) are visible in the duodenal specimen. Original magnification 40×
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4697037&req=5

Figure 0001: A – The biopsy specimen from the duodenum taken during the first hospitalisation in the Children's Memorial Heath Institute. Duodenal villi are normally formed with the absence of inflammation, the number of IELs is significantly increased, varying from 30 up to 50 lymphocytes per 100 enterocytes. Original magnification 20×. B – Increased number of IEL stained with anti-CD3 antibody (red colour) are visible in the duodenal specimen. Original magnification 40×
Mentions: A 14-year-old girl was admitted to the regional hospital due to chronic diarrhoea persisting for 5 weeks. The physical examination at admission revealed no abnormalities apart from poorly developed subcutaneous tissue – both the body mass and the height at the 3rd percentile. The laboratory tests showed leucocytosis and eosinophilia with increased IgE level. To exclude CD, EMAs were done, and they were negative. The ultrasound imaging showed no abnormalities. Negative stool cultures excluded gastrointestinal infections. Bearing in mind the above laboratory results, colonoscopy without gastroduodenoscopy was performed. Histological examination showed chronic inflammation in the large intestine with polymorphic infiltrates, in which eosinophils dominated. The girl, with an initial discharge diagnosis of ulcerative colitis (UC), was given mesalazine and she was referred to the Department of Gastroenterology, Hepatology, and Feeding Disorders of the Children's Memorial Health Institute (CMHI) in Warsaw to extend the diagnostic workup. At first, complete serological testing according to the ESPGHAN guidelines for diagnosis of CD was performed (TGA-IgA, total IgA, and EMA, which were previously negative). Total IgA within normal limits, increased TGA-IgA (22 U/ml; normal range up to 10 U/ml), and slightly positive EMA in titre 1: 5, but negative in titre 1: 10, were found. Both gastroduodenoscopy and colonoscopy were performed. Histological examination revealed pathologic changes restricted to the duodenum. Although duodenal villi were normally formed with the absence of inflammation (Figure 1 A), the number of IEL was increased, varying from 30 up to 50 lymphocytes per 100 enterocytes (Figure 1 B). Thus, histological changes were classified as grade 1 according to the modified Marsh-Oberhuber classification. There were no abnormalities within the large intestine; therefore, the diagnosis of UC was excluded and the treatment with mesalazine was discontinued. The ordinary gluten-full diet was ordered, and 6 months later the girl was re-admitted to the CMHI in order to perform control gastroduodenoscopy. This time histopathological features were explicitly indicative of CD and classified as grade 3 C according to Marsh-Oberhuber classification. Either in duodenal bulb or in other parts of the duodenum flattened villi with significantly increased number of IEL (50 lymphocytes per 100 enterocytes) and moderate polymorphic infiltrates in the lamina propria were observed (Figure 2). Repeated serological tests showed increased level of TGA-IgA (16 U/ml) and negative EMA in titre 1: 5. Finally, CD was recognised. A gluten-free diet and a follow-up visit at the outpatient gastroenterology clinic were ordered. At present, the girl is doing well, the diarrhoea has stopped, and her nutritional status has improved.

View Article: PubMed Central - PubMed

Affiliation: The Children's Memorial Heath Institute, Warsaw, Poland.

AUTOMATICALLY GENERATED EXCERPT
Please rate it.

Celiac disease (CD) is a chronic autoimmune intestinal disease caused by intolerance to gluten... Such a diagnostic approach concerns patients who present with clinical CD symptoms and strictly fulfil the following criteria: 1) TGA-IgA are highly elevated (greater than 10 times the upper limit of normal values), 2) antibody positivity is verified by IgA anti-endomysial antibodies (EMA) from a blood sample taken separately from the initial test, 3) positive HLA-DQ2 or/and -DQ8 haplotypes are confirmed by genetic tests, and 4) the response to a gluten-free diet is observed... Increased IEL number is actually considered the most important histological feature indicative of CD because atrophy of small intestinal mucosa with an absence of normal intestinal villi may occur in many entities such as microvillus inclusion disease, autoimmune enteropathy, intolerance to food (e.g. cow's milk, eggs, or soya), and eosinophilic gastroenteritis... Negative stool cultures excluded gastrointestinal infections... Bearing in mind the above laboratory results, colonoscopy without gastroduodenoscopy was performed... At first, complete serological testing according to the ESPGHAN guidelines for diagnosis of CD was performed (TGA-IgA, total IgA, and EMA, which were previously negative)... Total IgA within normal limits, increased TGA-IgA (22 U/ml; normal range up to 10 U/ml), and slightly positive EMA in titre 1: 5, but negative in titre 1: 10, were found... Currently, EMA should be used only in selected cases, when the diagnosis of CD can be made without small intestine biopsy, i.e. in children and adolescents with symptoms suggestive of CD and with high TGA-IgA concentration > 10 times the upper normal limit... Thus, in patients with positive specific TGA-IgA antibodies and a lack of specific histological changes, a follow up biopsy should be done... Although in our patient HLA examination was not performed, in such atypical patients, molecular testing could be done due to its great negative predictive value (about 99% of patients have HLA-DQ2 and/or HLA-DQ8 haplotype)... Interestingly, the specimens taken during the second colonoscopy presented normal histological features, whereas chronic inflammation with polymorphic and eosinophilic infiltrates had been found in the large intestine when colonoscopy had been done at the regional hospital... However, the hypothesis that CD onset was initiated by inflammatory/allergic reactions to antigens other than gluten cannot be excluded... Although gluten is the main external trigger of CD, its intake does not fully explain the pathogenesis of the disease... The disease can develop at any time during life, irrespective of diet – whether including gluten proteins or not... Lahdenperä et al. have proven that a gluten-free diet, which improves mucosal lesions, does not correct the increased activation of pro-inflammatory mediators of CD.

No MeSH data available.


Related in: MedlinePlus