1. Introduction

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Gluten enteropathy, a.k.a. celiac or non-tropical sprue is an autoimmune disease of the small intestines which arise in genetically predisposed children and adults[1]. It is thought to be caused by immunological hypersensitivity to gluten-containing food [2]. The key aspects of the pathogenesis of the disease include the enzyme tissue transglutaminase (tTG). Intestinal tTG is a calcium-dependent enzyme that catalyzes hydrolysis (i.e., deamidation, conversion of the amino acid glutamine into glutamate) of glutamine residues. Gliadin, a protein rich in glutamine, is a specific substrate for this enzyme. tTG selectively deamidates the gliadin molecules trapped in lamina propria so that deamidated gliadin peptides are formed [3].

The complex of the gliadin and the tTG and deamidated gliadin peptides in association with HLA-DQ2 (or DQ8 and other) molecules can be more readily represented by gut mucosal T lymphocytes [4]. However, this process is not performed in healthy individuals. Gluten-sensitive CD4+ T cells are activated and a Th1 immune response develops associated with the production of large amounts of IFNγ leading to mucosal damage [4]. Activated Th lymphocytes support the differentiation of specific B-lymphocytes into plasmocytes secreting specific antibodies such as anti-gliadin antibodies (AGA), anti-tTG (anti-tTG), anti-deamidated gliadin peptides (anti-DGP) antibodies, etc. [5].

These antibodies are strongly celiac-related and could be employed not only in the diagnosing but also in managing and follow-up of the disease [5,6].

2. Description Of The Case Report

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We present a clinical case of a 40-year-old Caucasian woman, diagnosed with CD at the age of 3 years. She was administered to GFD for four years, then discontinued the diet and switched to a common diet. Then, she complained frequently of diarrheal episodes with predominantly spring-autumn character; and a persistent anemia. In 2013, she started to complain of diarrhea every day, with no pathological impurities, swelling of the limbs and pronounced flatulence. She presented at the Gastroenterology Clinic with the above-mentioned symptoms. The present status and imaging were normal. From the laboratory testing, we found iron deficient anemia - Hemoglobin 91 g/l, Iron 4.6 μmo/l. We observed also positive immunological markers in the blood - anti-tTG antibodies IgA+IgG (>200 U/ml, URL < 15 U/ml), anti-DGP IgA+IgG+IgM (304.5 U/ml, URL < 15 U/ml). Serum levels of IgA were within the reference range - 1.76 g/l (reference range: 0.71-3.60 g/l).Histological investigation showed partial atrophy of the villous apparatus and increased number of inter- and intraepithelial lymphocytes, which was congruent with the typical picture of CD[7] (Figure1)

Figure 1

The patient was discharged from the hospital with recommendations for hygienic-dietary regimen and strict adherence to a GFD. The patient was followed-up two months later by retesting for the immunological markers. Anti-tTG antibodies decreased to 140.0 U/ml and anti-DGP dropped to 95.8 U/ml (Figure 2). However, they stayed above the upper reference line. Serum IgA was unchanged - 1.36 g/l (0.71-3.60).

Figure 2

The patient was retested every year for the presence of celiac-related antibodies anti-tTG and anti-DGP after strict adherence to gluten-free diet and we observed that they dropped below the URL after one year of GFD and stayed in the reference range for the four year period of follow-up (Table 1).

Table 1

3. Discussion

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We presented a case of a 40-year-old female who has been diagnosed with CD in the childhood, but who has not maintained a GFD for about 33 years, with complaints of exacerbated gastrointestinal symptoms and persistent anemic syndrome. Diagnosis of CD was re-confirmed histologically and serologically (immunologically) in elderly. Due to the common presence of IgA deficiency along with CD, the former was excluded. After adherence to GFD and strict compliance of the patient, she has improved her condition and has reduced the antibody levels in two months. Firstly, their levels stayed above the URL, explained by both the persistence of the disease and the relatively short 2-month-period on GFD.

After CD diagnosis, patients need a permanent adherence to a GFD, and they should be monitored periodically and routinely for celiac-related antibodies to assess compliance with the diet [2]. For the follow-up, different celiac-related antibodies could be employed. However, anti-DGP antibodies have been shown to be more sensitive in unveiling compliance to GFD compared to anti-tTG, even though the latter showed the enhanced diagnostic sensitivity for CD [8]. However, in clinical practice, even strong positive anti-tTG IgA results did not necessarily correlate with the severity of villous atrophy, so they are unlikely to be useful for monitoring dietary adherence [9]. It is important to note that all antibody-based serologic tests are expected to normalize on GFD, so the test accuracy depends on ongoing gluten consumption [10]. Furthermore, if the antibodies do not normalize within a couple of months on GFD, the physician should suggest refractory CD. These findings, however, require further investigations. We should also point out that some CD patients may be negative for celiac-related antibodies, which is not our case. The explanations for these CD patients with villous atrophy but without positive auto antibodies are GFD administration at the time of testing, IgA deficiency, non-celiac enteropathy or just seronegative CD [1].

4. Conclusion

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Combine testing of antibodies related to CD, a.k.a. a multiplex immunoassay improves patient diagnosis. Moreover, repeated antibody testing can be used for monitoring the effect of the GFD and the clinical course and severity of the disease. Our patient was advised to monitor antibodies at least every 3-12 months, and also to keep under observation the bone density and for neurological manifestations of the disease.

References

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