Group Of Celiac Patients Research Articles

Reproductive complications in celiac disease patients in Slovenia

ObjectiveCeliac disease is associated with higher risk of infertility, recurrent abortions, and adverse outcomes in pregnancy and in puerperium. The aim of the study was to analyse the association between celiac disease and reproductive disorders in the group of celiac patients and compare these to healthy controls. MethodsA retrospective case-control matched study. The association between celiac disease and menstrual cycle, gyneco-obstetrical complications was assessed with a questionnaire specifically developed for the study. 144 celiac women and 61 celiac men, members of Slovenian Celiac Society, together with 71 healthy women and 31 healthy men participated in the study. ResultsA higher percentage of celiac women (27.1%) had difficulties in conception of the first child when compared to healthy controls (12.7%) (p = 0.042). In addition, celiac women experienced more complications than healthy controls during the pregnancy, such as abortions or intrauterine growth retardation (p < 0.005). In our study, the prevalence of reproductive problems was not the same in celiac males and females. Altogether 2 celiac men (3.3%) reported having fertility problems, however, the difference between male cases and controls was not statistically significant (p = 0.548). ConclusionPhysicians should examine women with unexplained infertility, recurrent abortions or intrauterine growth retardation for undiagnosed celiac disease. Compared with healthy women, women with celiac disease have increased risk of spontaneous abortions, preterm delivery and fewer successful pregnancies.

Are Treated Celiac Patients at Risk for Mycotoxins? An Italian Case-Study.

Urinary biomarkers of mycotoxin exposure were evaluated in a group of celiac patients (n = 55) and in a control group of healthy subjects (n = 50) following their habitual diet. Deoxynivalenol (DON), zearalenone (ZEN), and fumonisin B1 (FB1) were monitored in 105 urinary samples collected from the two groups. Dietary habits were also recorded through compilation of a seven-day weighed dietary diary. Biomarkers of mycotoxin exposure were detected in 21 celiac patients and in 15 control subjects, corresponding to about 34% of total participants. In particular, ZEN was the most detected mycotoxin among all the studied subjects with a total of 19 positive cases. Results did not show a statistically significant difference in mycotoxin exposure between the two groups, and the presence of specific mycotoxins was not related to the intake of any particular food category. Our findings suggest little urgency of specific regulation for gluten free products, although the prevalence of exposure observed in free-living diets of both celiac and healthy subjects underlines the need of a constant surveillance on mycotoxins occurrence at large.

Pharmacotherapy and management strategies for coeliac disease

Introduction: Coeliac disease is a common disease that affects approximately 1% of Northern European and American populations. Evidence suggests it is caused by an inappropriate immune response in genetically susceptible patients to dietary gluten found in wheat, rye, barley and, in a small minority of patients, oats. Treatment involves a lifelong gluten-free diet. This diet limits nutritional variety and is costly and difficult to maintain.Areas covered: This review covers the current treatment options available and discusses novel emerging therapies for coeliac disease.Expert opinion:Novel therapies are still in early stages of development and therefore, at present, a gluten-free diet remains the treatment of choice in coeliac disease due to its low side-effect profile. A replacement for a gluten-free diet would be superior to an adjunct; in this case dietary modification of gluten may well have the least side effects, be tolerated by a wider group of coeliac patients and therefore be accepted.Search terms used: Pubmed, Medline and clinicaltrials.gov were searched with ‘celiac disease’ and ‘therapy’ as MESH terms. Patent database was searched using the term ‘celiac disease’. Conference attendance at DDW Chicago 2011 and Columbia 2010 was also used to gain further information from conference abstracts.

Serologic screening and genetic testing among brazilian patients with celiac disease and their first degree relatives

Celiac disease susceptibility has been shown to be associated with the HLA alleles DQA1*0501 and DQB1*0201 (together encoding the DQ2 heterodimer) that are present in practically all celiac disease patients. The DQ8 heterodimer (coded by DQA1*03-DQB1*0302), which is carried on a DRB1*04 (DR4) haplotype, is commonly encoded for by the few celiacs who do not carry the DQ2 heterodimer. Only a few celiac disease patients have been reported without these known risk alleles. To assess the prevalence of celiac disease in a group of first degree relatives of celiac patients, and the frequency of HLA predisposing alleles both in the group of celiac patients and in their first degree relatives, identifying those first degree relatives who would need further screening for celiac disease. Ninety celiac disease patients and 207 first degree relatives underwent serologic screening for celiac disease (endomysial and transglutaminase antibodies) followed by intestinal biopsy in positive patients. The HLA-DQA1*0501, DQB1*0201 and DRB1*04 frequencies of celiac patients and their first degree relatives were determined utilizing the PCR method. All the celiac disease patients (n = 90) with the exception of one (1.1%) carried at least one of the alleles investigated. Altogether 11 (5.3%) of the investigated first degree relatives did not carry any of the alleles studied. Fourteen (6.7%) new cases of celiac disease were found among the 207 celiac disease patients first degree relatives. Considering the cost-benefit of the HLA typing of all the first degree relatives of celiac patients, their HLA status should be decided on an individual basis, taking account of their profile and preferences, and the existence of other medical conditions.

Stem cell transplantation in the treatment of gastrointestinal diseases

The stem cells with self-renewal ability are capable to form one or more cell types. They will be in the target of cell and gene therapy because of their multipotency and easy retrieval. Application of adult mesenchymal, neuronal, epidermal and haematopoietic stem cell can be favourable in the treatment of cardiac (myocardial infarction), bone (osteoarthritis), neurological (Parkinson's, Alzheimer's) and hematological (hemophilia, thrombocytopenia) disorders. Authors summarize the knowledge in connection with their application in the therapy of gastrointestinal diseases. Haematopoietic stem cell transplantation has been successful for the treatment of refractory Crohn's disease, as well as in selected group of celiac patients. Mesenchymal stem cell transplantation has been proved beneficial in the prevention of liver fibrotic process. It will gain more grounds in the treatment of autoimmune liver diseases: autoimmune hepatitis, primary biliary cirrhosis and primary sclerosing cholangitis in the future. Well-designed, multicentric, prospective studies are needed to confirm the results of case reports and clinical studies with small group of patients.

Enfermedad inflamatoria intestinal en pacientes celíacos

A potential association between celic disease and inflammatory bowel disease hs been suggested, which may explain the fact that both disorders occasionally present in one patient or in his/her first-degree relatives more frequently than expected. To establish the prevalence of Crohn s disease and ulcerative colitis in celiac patients and their relatives. A cross-sectional, prospective epidemiological study in a group of celiac patients, their first-degree relatives, and a control group with similar epidemiological characteristics including the relatives of patients presenting at the ER for acute conditions. A semistructured interview was used to identify the presence of Crohn s disease and ulcerative colitis in celiac patients and their relatives. In all, 86 celiac patients and 432 relatives were included, who were compared to 809 control subjects (129 patients with acute conditions and 680 first-degree relatives). Three cases of Crohn s disease were identified among celiac patients, and 4 cases among their relatives. Only 1 case of Crohn s disease was detected in the control group (p < 0.01). No cases of ulcerative colitis were detected in any of the study groups. Patients with celiac disease and their relatives have a greater predisposition to Crohn s disease versus the control population.

Gluten sensitivity in a subset of children with insulin dependent diabetes mellitus.

The association between celiac disease and insulin dependent diabetes mellitus (IDDM) is well established. Rectal gluten challenge has been used in patients with celiac disease and in first degree relatives as a tool to assess the mucosal immune response to gluten. The aim of this study was to assess the mucosal immune response to gluten in IDDM children by rectal gluten challenge. Rectal biopsy specimens were obtained from 19 children with IDDM before and 6 h after rectal challenge with 2 g of a peptic tryptic digest of gliadin. A total of 16 treated celiac patients and 10 control subjects were also investigated. Epithelium and lamina propria CD3(+) and gamma delta(+) lymphocytes were counted with reference to a standard reference area of muscularis mucosae (10(4) microm(2)). After a local instillation of gliadin, a significant (>mean + 1 SD) percentage increment of lamina propria and epithelium CD3(+) and of lamina propria and epithelium gamma delta(+) lymphocytes was observed in five IDDM children, as compared to 11 and 13 celiac patients and one and two controls, respectively. A discriminant analysis allowed correct classification of 100% of patients with celiac disease and controls. The same analysis classified four of 19 IDDM children in the group of celiac patients. The positivity was associated with normal serology (antigliadin antibody, antiendomysial antibody, and antitissue transglutaminase antibodies) and a morphologically normal jejunal mucosa. All four patients had HLA-DQ alleles associated with celiac disease. Approximately 20% of IDDM children react to rectal instillation of gliadin. Long term follow-up is necessary to establish whether these subjects are at increased risk for developing celiac disease.

Gluten sensitivity in a subset of children with insulin dependent diabetes mellitus

Objectives The association between celiac disease and insulin dependent diabetes mellitus (IDDM) is well established. Rectal gluten challenge has been used in patients with celiac disease and in first degree relatives as a tool to assess the mucosal immune response to gluten. The aim of this study was to assess the mucosal immune response to gluten in IDDM children by rectal gluten challenge. Methods Rectal biopsy specimens were obtained from 19 children with IDDM before and 6 h after rectal challenge with 2 g of a peptic tryptic digest of gliadin. A total of 16 treated celiac patients and 10 control subjects were also investigated. Epithelium and lamina propria CD3 + and γδ + lymphocytes were counted with reference to a standard reference area of muscolaris mucosae (10 4 μm 2). Results After a local instillation of gliadin, a significant (>mean + 1 SD) percentage increment of lamina propria and epithelium CD3 + and of lamina propria and epithelium γδ + lymphocytes was observed in five IDDM children, as compared to 11 and 13 celiac patients and one and two controls, respectively. A discriminant analysis allowed correct classification of 100% of patients with celiac disease and controls. The same analysis classified four of 19 IDDM children in the group of celiac patients. The positivity was associated with normal serology (antigliadin antibody, antiendomysial antibody, and antitissue transglutaminase antibodies) and a morphologically normal jejunal mucosa. All four patients had HLA-DQ alleles associated with celiac disease. Conclusions Approximately 20% of IDDM children react to rectal instillation of gliadin. Long term follow-up is necessary to establish whether these subjects are at increased risk for developing celiac disease.

Atrophy of the coeliac mucosa.

Details of 12 patients suffering from atrophy of the coeliac mucosa (ACM) are presented. These patients failed to respond to the elimination of gluten from their diets. Their jejunal biopsies were examined in detail with particular attention given to Paneth cell numbers, crypt length, mitotic rate and mucosal thickness. These biopsies were compared with the biopsies of responsive coeliac patients. The ACM patients were found to have a statistically significant reduction in Paneth cell numbers (P < 0.0005), reduced crypt length (P < 0.0125), reduced mitotic rate (P < 0.0005) and a thinner mucosa (P < 0.0005), when compared with the responsive coeliac group. In addition the ACM group had a lower albumin level compared with the responsive group (P < 0.0005). Most of the ACM patients responded when treated with oral corticosteroids. It is considered that the above features are markers of a non-responsive group of coeliac patients and thus might be useful for identifying those patients who may benefit from early treatment with oral corticosteroids if gluten withdrawal is not rapidly effective.

TNF2, a polymorphism of the tumour necrosis-alpha gene promoter, is a component of the celiac disease major histocompatibility complex haplotype.

Celiac disease (CD) is an immune disease triggered by the cereal antigen gliadin, resulting in villous atrophy in the small intestine. Susceptibility to the development of CD is strongly influenced by genes in the major histocompatibility complex, in particular alleles of the DQ genes in the class II region. However recent evidence has suggested that the major histocompatibility complex (MHC) class III region may be linked to celiac disease independently of the class II region. Among the genes located in this area is TNF-alpha, which encodes the cytokine tumor necrosis factor-alpha which has a broad range of pro-inflammatory, immunomodulatory and catabolic activities. Therefore, aberrant expression of TNF-alpha could be important in the pathogenesis of MHC-associated immune disorders. A TNF-alpha variant with a polymorphism in its promoter region has been described and designated TNF2. TNF2 has been associated with a variety of MHC-linked diseases, including systemic lupus erythematosus, dermatitis herpetiformis and insulin-dependent diabetes mellitus (IDDM), as well as parasitic infections. TNF2 has previously been shown to be associated with the MHC haplotype HLA A1-B8-DR3-DQ2, which confers susceptibility to CD. We have analyzed the distribution of TNF2 alleles in a group of celiac patients (n = 52) compared to controls (n = 52) in an effort to evaluate its role, if any, in susceptibility to the condition. TNF2 has a frequency of 0.5000 (SE +/- 0.0490) in CD, compared to 0.1635 (+/- 0.0362) in a control sample (p < 10(-6)). Of 52 patients, 44 carried one or more TNF2 alleles. Analysis indicates that the distribution of TNF2 is best explained by assuming 100% allelic association between it and HLA-DQB1*0201 (frequency = 0.7791 +/- 0.0447). However, the number of TNF2 heterozygotes significantly exceeds expectations and measurements of linkage disequilibrium confirm that allelic associations spanning the DQ and TNF regions are strongly maintained in CD. Taken together, these results indicate that TNF2 may have a role in the pathogenesis of CD; however, since it is not an independent association, the possibility that TNF2 constitutes a passive component of the CD haplotype cannot be excluded.

Intakes of nutrients and nutritional status in coeliac patients.

The intake of nutrients and the nutritional status of untreated coeliac patients and coeliac patients in remission were investigated at Kuopio University Hospital. Forty untreated and 52 coeliac patients in remission were admitted to the study. The control group included 77 persons. Four-day food records, anthropometric measurements, and blood biochemistry were examined to obtain nutrient intake and nutritional status. Concentrations of serum ferritin, vitamin B12, and erythrocyte folate were lower in patients with untreated coeliac disease than in those in remission. Altogether, 15-38% of the untreated patients but only 0-20% of the patients in remission had levels of haemoglobin, serum ferritin, iron, vitamin B12, or erythrocyte folate below the reference values. No difference in anthropometric measurements was found between the two groups of coeliac patients. Except for some subclinical abnormal values in biochemical analyses in 20-38% of coeliac patients, nutritional status was quite normal in both groups of coeliac patients.

Increased concanavalin A induced suppression in treated and untreated coeliac disease.

The generation of suppression by concanavalin A in peripheral blood mononuclear cells in treated and untreated coeliac subjects using an in vitro assay was found to be significantly increased when compared with controls. The response of peripheral blood mononuclear cells to the plant mitogen concanavalin A (con A) was also significantly depressed in both groups of coeliac patients. It is proposed that the depressed cell mediated immunity found in this and other studies in coeliac patients is because of increased suppression. The possible connection between these findings and the increased incidence of malignancy also found in coeliac disease is discussed.

HLA antigens in coeliac disease associated with malignancy.

Coeliac patients are at greater risk than the general population of developing malignant neoplasms, particularly lymphomas. The establishment at the Clinical Research Centre of a national collaborative study of coeliac patients with malignancy provided the opportunity to carry out HLA typing for 55 HLA-A, B and C and the 10 recognised DR antigens on a group of coeliac patients with malignancy. Study of a sample of 44 patients with biopsy proven coeliac disease and histologically confirmed malignancy, including 12 with malignant histiocytosis, and 57 coeliac patients without malignancy, failed to show any significant differences in antigen frequencies between patients with and without malignancy. These results indicate that there are no HLA genetic markers associated specifically with the development of malignancy in coeliac disease.

Ultrastructural analysis of plasma cells in coeliac patients.

By accurate morphometry the length of the rough endoplasmic reticulum (RER) was estimated in electron micrographs of a population of jejunal plasma cells in biopsies obtained from normal volunteers, untreated coeliac disease patients, and coeliac disease patients treated for one year on a gluten free diet. Increase in length or hypertrophy of the endoplasmic reticulum is an indication of increased protein synthesis of the cell (Ghadially, 1977). An increase compared with normal length was demonstrated in the mean length of the plasma cell rough endoplasmic reticulum in plasma cells obtained from both groups of coeliac patients. This estimate of increased protein production--in this case immunoglobulin--indicates an increase in the immunological activity of plasma cells even after treatment and suggests not only a reaction to dietary gluten but probably to other antigens also.

Morphometric Electron and Light Microscope Analysis of Lymphoid Cells in Coeliac Disease

Lymphocytes in jejunal biopsies from normal subjects and from untreated, treated, and gluten-challenged coeliac patients were examined by accurate morphometric methods. There was no significant difference between lymphocytes from different sources and those in the jejunum. Transforming lymphocytes were ultrastructurally quite different from non-transforming lymphocytes. The appearance of transforming lymphocytes in the lamina propria in different groups of coeliac patients is in accordance with the increase in the number of plasma cells. In treated patients the results indicate a rapid humoral response to gluten challenge.