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1.
OBJECTIVE--To investigate the extent to which the detection of antibodies to gliadin, endomysium, and jejunum predicts the eventual diagnosis of coeliac disease according to the revised ESPGAN diagnostic criteria in a group of patients in whom there is a high suspicion of coeliac disease. DESIGN--Clinical assessment and laboratory analysis of patients with suspected coeliac disease. SETTING--Gastroenterology department of teaching hospital. PATIENTS--96 adults with suspected coeliac disease attending for jejunal biopsy. MAIN OUTCOME MEASURES--Diagnosis of coeliac disease with the revised criteria of the European Society of Paediatric Gastroenterology and Nutrition in patients with and without antibodies associated with coeliac disease. RESULTS--28 patients had a clinical diagnosis of coeliac disease, seven of other gastrointestinal diseases, and 12 of miscellaneous diseases; 49 had no diagnosis. Gliadin IgA detected by ELISA was found in all patients with coeliac disease and none of those without, giving a sensitivity, specificity, positive and negative predictive values, and predictive efficiency of 100% for diagnosing coeliac disease within the group. Endomysial IgA was found in 25 (89%) patients with coeliac disease and jejunal IgA in 21 (75%); neither IgA was found in patients without coeliac disease. CONCLUSION--Detection of gliadin IgA by ELISA and to a lesser extent the endomysial IgA should allow better selection of patients for jejunal biopsy and thus make diagnosing coeliac disease simpler and more efficient.  相似文献   

2.
Circulating IgA-antigliadin antibodies were detected with enzyme linked immunosorbent assay (ELISA) in four of 121 patients (3%) who had IgA mesangial nephropathy and 14 of 17 children (82%) who had untreated coeliac disease. No positive cases were present in the 54 healthy subjects of the control group. Three patients who had IgA nephropathy and IgA-antigliadin antibodies underwent jejunal biopsy, and two showed mucosal atrophy. In these two patients urinary abnormalities, together with the IgA-antigliadin antibodies, disappeared completely after three months and five months, respectively, of following a gluten free diet. Circulating IgA immune complexes were found in most patients who had coeliac disease and Berger''s disease associated with IgA-antigliadin antibodies, suggesting overactivity of the B cells producing IgA in both conditions. By contrast, a circulating IgA rheumatoid factor was detectable in three of the four patients who had IgA nephropathy and asymptomatic coeliac disease but was always absent in children who had coeliac disease but did not show signs of renal disease. These results suggest that a more complex abnormality in the IgA immune response is necessary for renal disease to become manifest in patients who have gluten enteropathy.  相似文献   

3.
Diabet. Med. 29, e286-e289 (2012) ABSTRACT: Aims To determine the incidence of coeliac disease in young people with Type?1 diabetes and to examine the effect of age at diabetes onset and disease duration. Methods This was a clinic-based observational cohort study of 4379 people aged ≤?18?years (49% male) between 1990 and 2009 from Sydney, Australia. Screening for coeliac disease was performed at diagnosis and 1-2?yearly using anti-endomysial and/or anti-tissue transglutaminase immunoglobulin?A (IgA) antibodies. Coeliac disease was diagnosed by small bowel biopsy based on Marsh score ≥?III. Results Coeliac disease was confirmed by biopsy in 185; of these, 61 (33%) were endomysial or tissue transglutaminase IgA antibody-positive at diabetes diagnosis. Mean age at diabetes onset was 6.6?±?4.0 vs. 8.4?±?4.1?years in those without coeliac disease (P?相似文献   

4.
Celiac disease is a chronic illness of the small bowel caused by gliadin intolerance in genetically predisposed subjects. The aim of this study was to investigate serum levels of IgA and IgG antigliadin antibodies, IgA antiendomysial antibodies, and IgA anti-tissue transglutaminase antibodies in 169 patients with autoimmune thyroid diseases, i.e. chronic thyroiditis and Graves' disease. Antiendomysial antibodies were positive in 2 out of 169 persons (1.18%), IgA antigliadin antibodies in 15.98%, IgG antigliadin antibodies in 51.48%, and IgA anti-tissue transglutaminase in 14.79%. The prevalence of positivity was higher compared to the 1312 control blood donors described in our previous study (Vancíková et al. 2002) (p<0.05). Patients with chronic thyroiditis treated with a high replacement dosage of levothyroxin (125-200 microg daily) had higher serum levels of IgA antigliadin antibodies in comparison with patients treated with a lower dosage (50-100 microg daily) (medians: 13.00 vs. 19.69, p=0.033). We found a negative correlation of IgA anti-tissue transglutaminase antibodies and total calcium serum levels (r = -0.480, p=0.0236, n=22). We can conclude that in persons with autoimmune thyropathy there is a high prevalence of positive antigliadin, anti-tissue transglutaminase and antiendomysial antibodies. Latent celiac disease may lead to impaired resorption of therapeutically administered levothyroxine, calcium, or other substances.  相似文献   

5.
6.
Diagnosis of coeliac disease (CD) relies on a combination of clinical, genetic, serological and duodenal morphological findings. The ESPGHAN suggested that biopsy may not be necessary in all cases. New guidelines include omission of biopsy if the concentration of CD-specific antibodies exceeds 10 times the upper limit of normal (10 ULN) and other criteria are met. We analysed the 10 ULN criterion and investigated multiple antibody-assays. Serum was collected from 1071 children with duodenal biopsy (376 CD patients, 695 disease-controls). IgA-antibodies to tissue transglutaminase (IgA-aTTG), IgG-antibodies to deamidated gliadin peptides (IgG-aDGL) and IgA-endomysium antibodies (IgA-EMA) were measured centrally. We considered 3 outcomes for antibody test procedures utilizing IgA-aTTG and/or IgG-aDGL: positive (≥10 ULN, recommend gluten-free diet), negative (<1 ULN, no gluten-free diet) or unclear (perform biopsy). Positive (PPV) and negative (NPV) predictive values were based on clear test results. We required that they and their lower confidence bounds (LCB) be simultaneously very high (LCB >90% and PPV/NPV >95%). These stringent conditions were met for appropriate antibody-procedures over a prevalence range of 9–57%. By combining IgG-aDGL with IgA-aTTG, one could do without assaying total IgA. The PPV of IgG-aDGL was estimated to be extremely high, although more studies are necessary to narrow down the LCB. The proportion of patients requiring a biopsy was <11%. The procedures were either equivalent or even better in children <2 years compared to older children. All 310 of the IgA-aTTG positive children were also IgA-EMA positive. Antibody-assays could render biopsies unnecessary in most children, if experienced paediatric gastroenterologists evaluate the case. This suggestion only applies to the kits used here and should be verified for other available assays. Confirming IgA-aTTG positivity (≥10 ULN) by EMA-testing is unnecessary if performed on the same blood sample. Prospective studies are needed.  相似文献   

7.
A way of coeliac disease diagnosis was assessed in 348 children, Only 14% of patients has been examined according to ESPGAN recommendations and in the proper time. Diagnosis has been completed in 123 patients, and coeliac disease has been diagnosed only in 38 of them. The I biopsy has not been performed in 96 children, the II biopsy--in 136 children, gluten-free diet has not been observed in 105 children after the I biopsy. Other causes of diagnostic failures included: prolongation of the consecutive stages and improper histological evaluation, change of biopsies order, erroneous clinical evaluation. Diagnosis according to ESPGAN recommendations is practically very difficult and time consuming. Immunological markers of coeliac disease (IgA EmA, ARA) should lead to simplification and adjustment of those recommendations in Poland.  相似文献   

8.
The gastrointestinal disorder coeliac disease (CD) is induced by the ingestion of wheat gluten and is characterized by damage of the typical structure of the intestinal mucosa. The enzyme tissue transglutaminase (tTGase) was identified as the major target of disease-specific antibodies in-patients. We performed an epitope fine-mapping with a series of pentadecapeptides synthesized using parallel multiple peptide synthesis. For the detection of biomolecular interactions a label-free parallel method, reflectometric interference spectroscopy (RIfS), was used. This is the first optical label-free method adapted to a high throughput screening (HTS) format and the experimental results demonstrate its applicability as a biological screening device. A high titer of anti-tTGase antibodies is found in the serum of coeliac patients. We have taken the first step towards a fast non-surgical test for the detection of these antibodies. In order to identify and characterize a continuous epitope with high affinity against the anti-tTGase antibody a screening of 21 pentadecapeptides has been accomplished with the parallel RIfS system. A single channel RIfS-system with high resolution was used to determine binding constants of identified peptides with high affinity.  相似文献   

9.
ObjectivesTo provide evidence of underdiagnosis of coeliac disease and to describe the main presenting symptoms of coeliac disease in primary care.DesignCase finding in a primary care setting by testing for coeliac disease by using the endomysial antibody test.SettingNine surgeries in and around a market town in central England, serving a population of 70 000.ParticipantsFirst 1000 patients screened from October 1996 to October 1997.ResultsThe 30 patients (out of 1000 samples) with positive results on the endomysial antibody test all had histological confirmation on small intestine biopsy. The commonest mode of presentation (15/30) was anaemia of varying severity. Most patients (25/30) presented with non-gastrointestinal symptoms. Specificity of the endomysial antibody test was 30/30.ConclusionsUnderdiagnosis and misdiagnosis of coeliac disease are common in general practice and often result in protracted and unnecessary morbidity. Serological screening in primary care will uncover a large proportion of patients with this condition and should be made widely available and publicised. Coeliac disease should be considered in patients who have anaemia or are tired all the time, especially when there is a family history of the disease.

Key messages

  • General practitioners currently see many people with undiagnosed coeliac disease
  • The most likely presentation is a combination of microcytic anaemia, past or present, a family history of the disease, and feeling tired all the time
  • Estimations of endomysial antibody and IgA are reliable diagnostic tools
  • The prevalence of coeliac disease in Britain is higher than the accepted figure of 1:1000 population
  • Increased awareness of the extra intestinal manifestations of coeliac disease, coupled with a low threshold for serological testing, will uncover a large portion of undiagnosed coeliac disease
  相似文献   

10.
Coeliac disease is the most common disorder with malabsorption of the small instestine, caused by the gluten fraction of cereals in genetically predisposed individuals. Gluten peptides are efficiently presented by coeliac disease-specific HLA-DQ2- and HLA-DQ8-positive antigen-presenting cells, and thus drive the antigen-presenting cells, predominantly in the connective tissue of the lamina propria. The studying of the recently explored autoantibodies against tissue transglutaminase brought us further in the understanding of the pathophysiology of coeliac disease. The spreading of reliable serologic methods modified our knowledge on the clinical picture and prevalence of the disease. Long-standing untreated coeliac disease, even if clinically silent, predisposes for other autoimmune diseases. Therefore, population screening for immunoglobulin A antibodies to tissue transglutaminase seems justified.  相似文献   

11.
The diagnostic value in coeliac disease of circulating antibodies to casein, crude gliadin, and alpha gliadin was assessed using an adaption of the enzyme linked immunosorbent assay system. alpha Gliadin was the only antigen which consistently separated 26 patients with untreated coeliac disease from 26 normal controls and 13 patients with chronic inflammatory bowel disease. The mean assay index for the 26 patients was 3.1 (SD 1.2) compared with 1.05 (0.5) for the normal controls and 1.1 (0.6) for patients with chronic inflammatory bowel disease. The alpha gliadin antibody levels of six patients with coeliac disease who had maintained a gluten free diet for at least two years were not significantly higher than normal (1.0 (0.4)). The validity of the test was determined in 90 consecutive patients who were being investigated for the presence of coeliac disease. Levels of alpha gliadin antibody were raised in 36 out of 44 patients found to have histologically proved coeliac disease and in six out of 46 subjects whose jejunal mucosa was normal. Serial alpha gliadin concentrations were measured in 12 patients with coeliac disease who had repeat jejunal biopsies performed six months after starting a gluten free diet. The levels of antibody fell in seven of the eight patients whose jejunal mucosa improved on maintaining the diet. They remained raised in four patients who did not adhere to the diet and whose mucosa did not improve. Although a test measuring alpha gliadin antibodies is unlikely to replace jejunal biopsy in the diagnosis of coeliac disease it may be useful in screening for the disease among outpatients.  相似文献   

12.

Introduction

The role of serological tests such as IgA anti-transglutaminase autoantibodies has become increasingly important in celiac disease (CD) diagnosis. However, the efficiency of these tests for patient follow-up is controversial. We investigated the correlation of 12 different serological tests, including recent deamidated gliadin and actin IgA tests, with villous atrophy (VA) in a retrospective cohort of treated celiac patients.

Materials and Methods

Serum samples were collected from 100 treated CD patients who had intestinal biopsy in the course of their follow-up. Antibodies against transglutaminase, deamidated gliadin peptides, and native gliadin were measured, along with IgA anti-actin. The biopsy slides were all blind-reviewed and scored according to Marsh classification.

Results

For all deamidated gliadin and transglutaminase tests, we found that a positive result was significantly associated with persistence of intestinal VA, with a diagnostic efficacy up to 80%. Furthermore, antibodies titers directly correlated with the degree of VA, indicating a strong link between disease activity and presence of antibodies in the serum. Interestingly, the tests with the highest association with persistent VA were those for deamidated gliadin IgG. Using a test positivity pattern analysis, we were also able to identify several groups of patients with distinct antibody profiles that showed significant differences in intestinal damage and diet compliance.

Conclusions

Altogether, these results show that deamidated gliadin antibodies are strongly correlated with VA and should be considered valuable tools in CD follow-up and that multiplex serologic analysis for treated CD represents a promising tool for personalized patient management.  相似文献   

13.
To assess the incidence and effects of continuing gluten ingestion in coeliac disease 51 adult coeliac patients were studied after four to 132 (mean 63) months on a prescribed gluten-free diet. Each patient completed a prospective dietary questionnaire, underwent a repeat jejunal biopsy, and gave serum for gluten antibody estimation. Altogether 65% of patients were still ingesting gluten, often inadvertently. Direct questioning on dietary habits had failed to uncover most of this consumption. The gluten antibody test proved a useful screening test for detecting continuing gluten ingestion and patients with both persistent subtotal villous atrophy and gluten antibodies were almost certain to be taking large amounts ( more than 2 g/day). The presence of persistent partial villous atrophy was found, however, to be an unreliable guide to gluten intake.  相似文献   

14.
Celiac disease is an autoimmune disorder in which gluten peptides presented by specific HLA-DQ2- and HLA-DQ8-positive antigen presenting cells elicit immune response in connective tissue of lamina propria. Immunoglobulin A (IgA) antiendomysial antibodies are specific for celiac disease and are used for screening, diagnosis and follow-up of this disease with an almost 100% sensitivity and specificity. The major target antigen of IgA antiendomysial antibodies was identified as tissue transglutaminase; nevertheless, the existence of the additional unique celiac disease-specific autoantigens is anticipated. In this study we have utilized a proteomic approach in order to search out new autoantigens recognized by serum antibodies of patients with active celiac disease. We report the detection of 11 proteins that were immunorecognized with various frequencies by sera of patients with celiac disease. Four autoantigens were identified by mass fingerprinting approach as actin, ATP synthase beta chain and two charge variants of enolase alpha. While production of IgA antibodies against actin molecules were described earlier, the existence of autoantibodies to ATP synthase beta chain and enolase alpha species in sera collected from patients with active celiac disease are described for the first time. These results are suggestive of the existence of additional celiac disease autoantigens with possible diagnostic utility.  相似文献   

15.
Coeliac disease (CD) is a T-cell mediated immunological disease of the small intestine which is triggered in susceptible individuals by ingestion of gluten. The pathogenic mechanism of coeliac disease, and the role that alpha-gliadin specific T cells play in mucosal lesions and their involvement in peripheral blood is not yet explained at all. Previous studies have reported proliferative response to alpha-gliadin measured with the classic assay of 3HTdR incorporation. We analysed the activation antigen CD69 on T cells from CD patients and normal individuals following stimulation with alpha-gliadin and different antigens (tetanus toxoid, peptides unrelated to gliadin and PHA). CD69 coexpression with T cell CD3+ and proliferation marker Ki67 was evaluated with time. CD69 coexpression with T cell CD3+, CD4+ and CD8+ was also evaluated. It was found that peripheral blood mononuclear cells (PBMC) of coeliac patients increased their percentage of CD69 positive T cells when stimulated with alpha-gliadin, in comparison with cells from controls. Significant T cell activation was found only in subjects not treated with the gluten free diet; a positive response was found also in two coeliac patients with selective IgA deficiency, anti-endomisium negative, without circulating IgA anti alpha-gliadin or anti-tissue transglutaminase antibodies. The CD69 expression after stimulation was compared with the standard method of 3HTdR incorporation. Our data show that CD69 expression is useful to asses a specific T cell response to alpha-gliadin in coeliac disease. in a very short time. Moreover, the method allows to investigate T cell response at the lymphocyte subsets level, which represents a useful tool in the diagnosis of coeliac disease.  相似文献   

16.
As an autoimmune disease, type 1 diabetes mellitus (DM) can be associated with other autoimmune disorders. The aim of this study was to detect subclinically associated autoimmune thyroid disease, coeliac disease, and Addison's disease. The presence of autoantibodies was evaluated with special regard to the control of diabetes and to the clinical status of the patient. Fifty-one type 1 diabetic patients (22 men, 29 women, mean age 37+/-11 years, mean duration of diabetes 16+/-13 years) were included into this study. Specific antibodies to islet antigens--glutamic acid decarboxylase (GAD65), protein thyrosine phosphatase IA-2alpha, and to thyroid autoantigens--thyroid microsomal peroxidase (TPO) and thyroglobulin (TG) and also thyroid stimulating hormone (TSH) were measured by RIA. Autoantigens of the small intestine--tissue transglutaminase autoantibodies (ATTG), IgA and IgG antibodies to gliadin (AGA-IgA, AGA-IgG) were evaluated by ELISA. Endomysial autoantibodies (EMA) and adrenal cortex antibodies (ACA) were detected by indirect immunofluorescence microscopy. Eleven new cases of thyreopathy (22 % of patients) were detected by the assessment of thyroid autoantibodies and TSH. Two new cases of thyreotoxicosis were diagnosed during the study. Coeliac disease was diagnosed in at least two cases. Addison's disease was not diagnosed, although the ACA were positive in two patients. No influence of single or combined autoantibody positivity on the control of diabetes was found if normal organ function was preserved. In both patients with thyreotoxicosis the control of diabetes was worsened and improved after treatment. The screening of autoantibodies in type 1 diabetic patients could reveal subclinical cases of AITD or coeliac disease. Subclinical forms of these disorders have no influence on diabetes control. However, impaired organ function may be associated with the worsened control of diabetes as we demonstrated on two newly diagnosed cases of thyreotoxicosis. We suggest the need for the follow-up of patients with positive autoantibodies because further deterioration of the respective organs can be expected.  相似文献   

17.
Thirty-five children, in whom coeliac disease had been diagnosed on inadequate grounds and who had been on a gluten-free diet for one to 10 years, were challenged with gluten in accordance with a standardised procedure. All children were admitted to hospital for 48 hours for general assessment, two one-hour blood xylose tests, and the introduction of gluten. Thirty children underwent a pre-challenge peroral jejunal mucosal biopsy; the specimens were either normal or showed slight non-specific abnormalities. Gluten powder 20 g/day was given in addition to an otherwise gluten-free diet. The children were reassessed as outpatients every two weeks, when a one-hour blood xylose test was performed. Repeat biopsy was performed when xylose absorption fell or after three months. Seventeen children had abnormal post-challenge biopsy appearances compatible with coeliac disease in relapse; 14 of these children completed their challenge within eight weeks. Seventeen children had completely normal biopsy appearances at the end of three months and were returned to a normal diet. One to two years later eight underwent repeat biopsies, which showed nothing abnormal. In only one child, the oldest in the series, were the histological findings equivocal. In the 17 children in whom coeliac disease was confirmed the duration of gluten challenge was not related to age, duration of gluten-free diet, histological findings on the pre-challenge biopsy, or HLA status.  相似文献   

18.
The latest consensus on celiac disease in 2008, under the auspices of the International Societies of Pediatric Gastroenterology, Hepatology and Nutrition, shows that HLA DQ2/DQ8 typing indicates the highest negative predictive value for celiac disease, which would exclude the diagnosis of celiac disease. In Romania, there are no studies on the implication of HLA-DQ2/DQ8 in celiac disease in children. The aim of our study was to analyze the significance of genetic tests, with a focus on negative HLA-DQ2/DQ8 cases, as well as to determine the main haplotypes involved in celiac disease in children. We tested in 37 children with old celiac disease, confirmed based on the presence of intestinal villi changes on duodenal biopsy, the IgA anti-tissue transglutaminase antibodies (TgA-IgA) by ELISA and the IgA anti-endomysium antibodies (EmA-IgA) by indirect immunofluorescence, compared to HLA-DQ2/DQ8 typing by polymerase chain reaction (PCR). In 25 children, the determined HLA haplotypes predominantly belonged to DQ2, and in 3 children we report the presence of a new haplotype, DR3-DQ2/DR4-DQ8, formed by pattern 1, DR3-DQ2-the DQA1*0501 and DQB1*0201 alleles, and pattern 5, DR4-DQ8-the DQA1*0301 and DQB1*0302 alleles. In 9 children, genetic tests were negative for celiac disease. The identification of HLA-DQ2/DQ8 provides additional data in the diagnosis of celiac disease, but a rigid algorithm in the diagnosis of celiac disease has no practical applicability.  相似文献   

19.

Purpose

Selective immunoglobulin A deficiency is the most common primary immunodeficiency disorder that is strongly overrepresented among patients with celiac disease (CD). IgG antibodies against tissue transglutaminase (tTG) and deamidated gliadin peptides (DGP) serve as serological markers for CD in IgA deficient individuals, although the diagnostic value remains uncertain. The aim of this study was to investigate the prevalence of these markers in a large cohort of IgA deficient adults with confirmed or suspected CD and relate the findings to gluten free diet.

Methods

Sera from 488,156 individuals were screened for CD in seven Swedish clinical immunology laboratories between 1998 and 2012. In total, 356 out of 1,414 identified IgA deficient adults agreed to participate in this study and were resampled. Forty-seven IgA deficient blood donors served as controls. Analyses of IgG antibodies against tTG and DGP as well as HLA typing were performed and a questionnaire was used to investigate adherence to gluten free diet. Available biopsy results were collected.

Results

Out of the 356 IgA deficient resampled adults, 67 (18.8%) were positive for IgG anti-tTG and 79 (22.2%) for IgG anti-DGP, 54 had biopsy confirmed CD. Among the 47 IgA deficient blood donors, 4 (9%) were positive for IgG anti-tTG and 8 (17%) for anti-DGP. Four were diagnosed with biopsy verified CD, however, 2 of the patients were negative for all markers. Sixty-eight of 69 individuals with positive IgG anti-tTG were HLA-DQ2/DQ8 positive whereas 7 (18.9%) of the 37 individuals positive for IgG anti-DGP alone were not.

Conclusions

IgG anti-tTG seems to be a more reliable marker for CD in IgA deficient adults whereas the diagnostic specificity of anti-DGP appears to be lower. High levels of IgG antibodies against tTG and DGP were frequently found in IgA deficient adults despite adhering to gluten free diet.  相似文献   

20.
We have used precipitin tests to detect antibodies to 10 dietary proteins in the serum (71 cases) and intestinal secretions (51 cases) of a group of children. Thirty-three of the patients had untreated coeliac disease. Our aims were to find out if, in coeliac patients, there was intestinal secretion of antibodies to wheat proteins only or if, as in coeliac serum, antibodies to many food proteins were present; and to confirm that secretion of antibodies to wheat or gluten was specific for coeliac disease.Precipitins to one or more dietary antigens were detected in the intestinal secretions of 26 out of 30 coeliacs and of 11 out of 21 children who did not have coeliac disease. Most of the positive reactions were with the antigens wheat flour, gluten, oatmeal, and egg. Though precipitins to wheat flour or gluten were present in the intestinal secretions of 22 out of 30 coeliacs this was not specific for coeliac disease for these precipitins were also present in 8 out of 21 non-coeliac children.Serum precipitins were detected in 27 out of 33 coeliacs (to the antigens wheat flour, gluten, oatmeal, rice flour, milk, bovine calf serum, sheep serum, and egg) and in 5 out of 33 non-coeliacs (mainly to milk and calf serum, but two infants aged 3 and 5 months had precipitins to several antigens).  相似文献   

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