Untreated CD Research Articles

The Assessment of Interleukin-15 and Interleukin-21 Gene Expression and Serum Level in Celiac Disease Prevalence Patients

Eighty-four Iraqi patients (Male & Female) with celiac disease with an age range (3-65) were investigated. Samples were taken from the Al Karama Teaching Hospital period October 2020 - to June 2021. Data sheet was filled according to questionnaire format, which include name, age, smoking, family history & alcohol intake. The patient's diagnosis was based on some serological test (AGA, tTG) the patients were clinically subdivided into treated and untreated. Twenty- seven controls were selected randomly from apparently healthy individual (31 male & 53 female). This study aims to evaluate evaluated some genetic & immunological parameters; her were: 1-Determine whether the gene expression and the serum level of interleukins (15 and 21) have an effect on the functioning of the immune system in individuals with celiac disease. 2-Evaluated CD gene expression of treated (gluten-free diet) and naive (untreated) CD patients compared with healthy individuals. The study methodology was based on an ELISA test kit provides a quantitative in vitro assay for human autoantibodies of the IgA class against tissue transglutaminase in serum or plasma. Result shown in Table (2) indicate that the majority of patients in celiac disease were diagnosed in females more than males; in the other hand, 66,67% of the confirmed treated Patients with celiac disease were females, while 33.33% were males, 40% confirmed untreated Patients from celiac disease were males when they were females 60 %, moreover furthermore 62.96% control female group more than 37.04% male control group with a significant difference (P-value 0.03661). The collected data showed that 23 (76.67%) patients had no clinical history of celiac disease in the untreated group; on the other hand, only 7 (23.33%) had a clinical history of the patient in the same group, while 1 (3.7%) ) The group of patients treated with no clinical history more than 26 (96.30%) and the patient in the same group had a clinical history, as well as 20 (74.07%) patients, had no history of celiac disease in the control group 7 (25.93%) Patients with a family history of celiac disease in the control group, with highly significant difference * (P≤0.05), ** (P≤0.01), (P-value 0.0001). he casuistic in table (3) showed the serum of 84 patients, including 30 with celiac disease without treatment tTG-IgA (5.41 ±0.27 b), tTG-IgG (3.76 ±0.27 b),27 patients treated group tTG-IgA (10.65 ±1.84 a), tTG-IgG (7.31 ±1.46 a) and 27 healthy as controls tTG-IgA (3.62 ±0.19 b), tTG-IgG (2.72 ±0.17 b), with P-value tTG-IgA (0.0001), tTG-IgG (0.0007), within significantly high difference ** (P≤0.01). The variants represented IL-15 and IL-21 gene expressions of celiac patients untreated, treated group, compared with that in the healthy control group individuals. The results showed that of IL-21 expression in untreated patients was (27.22 ±0.23 a) tables (6) and (7), while treated group (27.37 ±0.24 a), more than control group (25.04 ±0.53 b), with high significant P-Value (P≤0.01). At the same time, the expression of the IL-15 gene in untreated patient was (29.50 ±0.40), while treated group (29.63 ±0.26a) and control group (29.04 ±0.81), with non-significant P-Value (P≤0.706).

Exogenous Melatonin Supplement Contributes as Antioxidant to Attenuate the Oxidative Stress Induced by Cadmium Toxicity in Male Wistar Rats

Abstract Background: Melatonin is a peptide neurohormone naturally synthesized in the brain by the pineal gland. The basic function of melatonin is related to the causation and regulation of the sleep–wake cycle (circadian cycle). Cadmium (Cd) is a hazardous heavy metal and its toxic effects induce extensive tissue damage. The present study was undertaken to elucidate the efficiency of exogenous melatonin in attenuating Cd-induced oxidative stress. Methods: The experimental rats were allotted into four groups (n = 20), designated as untreated control, melatonin accessed, Cd exposed, and Cd exposed with access. Results: The hematological and biochemical parameters (serum and tissues) of Cd-exposed rats were significantly altered. Cd-exposed rats that received melatonin demonstrated increased erythrocytic indices; showed significantly increased levels of total proteins, catalase, total thiols, and glutathione; and exhibited decreased levels of blood Cd, urea, creatinine, bilirubin, malondialdehyde, and hydrogen peroxide. Conclusions: It was concluded that melatonin has an efficient antioxidant activity in attenuating oxidative stress induced by Cd.

Effect of gluten-free diet on levels of soluble CD14 and lipopolysaccharide-binding protein in adult patients with celiac disease.

IntroductionCeliac disease (CD) is an autoimmune enteropathy triggered by gluten ingestion in genetically susceptible individuals. In CD, activation of the immune response causes damage of the intestinal mucosa, and a gluten-free diet (GFD) is the only available therapy. Intestinal damage can lead to an increase in the circulation of components of bacteria from the intestinal lumen, such as lipopolysaccharide (LPS). Soluble CD14 (sCD14) and lipopolysaccharide-binding protein (LBP) participate in the recognition of LPS, and their levels are altered in different pathologies. In the present study, the circulating levels of sCD14 and LBP from untreated CD patients were evaluated and compared to CD patients on a GFD and controls.Material and methodsIn total seventy-two adult patients with CD, twenty-three untreated CD patients and forty-nine on a GFD were included. In addition, fifty-five healthy individuals were included as controls. Additionally, the effect of LPS on sCD14 production by both normal and inflamed intestinal tissue culture was explored.ResultsSerum levels of sCD14 were found to be significantly increased in untreated CD patients compared to patients on a GFD and controls. In addition, we found that LPS induced the production of sCD14 by biopsies of intestinal tissue from untreated CD patients.ConclusionsThe data from this study show that circulating levels of sCD14 are increased in the untreated CD patients compared to patients on a GFD. Our data show that LPS induces the production of sCD14 by the intestinal tissue from untreated CD patients.

Serum IL-21 levels from celiac disease patients correlates with anti-tTG IgA autoantibodies and mucosal damage

Objectives: Coeliac disease is a multifactorial disorder influenced by environmental, genetic and immunological factors. Interleukin (IL)-21 has been linked to an increase disease risk and the serum level of IL-21 seems to be increased in CD compared to a healthy control population.Methods: Sera were collected from 160 CD patients, 120 untreated and 40 following a gluten-free diet, and form 45 healthy subjects. Serum IL-21 was evaluated by specific ELISA tests.Results: Our data show that patients with untreated CD display IL-21 concentrations significantly higher than both treated-CD patients (following a gluten-free diet) and controls. In addition, serum IL-21 correlates with serum titres of anti-tTG IgA autoantibodies. Finally, our results show a correlation of this cytokine with duodenal mucosal damage.Conclusions: A role of gluten, as antigen with stimulatory function on IL-21 production, seems to be confirmed by the longitudinal analyses showing that the gluten-free diet decreases to a nearly undetectable amount this cytokine. In addition, the finding of a positive correlation between the serum amount of IL-21 and the grade of duodenal mucosa damage suggests a strong immunomodulatory effect of this cytokine on cytotoxic T lymphocyte functions. This study provides an extra evidence to emerging data on the potential role IL-21 in CD pathogenesis, suggesting its involvement in the development and progression of CD. Significance statement: In untreated CD, serum IL-21 shows higher levels compared with treated CD and healthy subjects. Serum amounts of IL-21 correlate with anti-tTG IgA autoantibodies and with duodenal mucosa damage.

Circulating microRNAs as potential non-invasive biomarkers in pediatric patients with celiac disease.

Celiac disease is an enteropathy induced by ingestion of gluten triggering an immune response in genetically predisposed individuals. MiRNAs are small non-coding RNAs that have a role as regulators of gene expression at the post transcriptional level. The aim of this study is to evaluate the possibility of using circulating miRNAs as non-invasive biomarkers in pediatric patients with celiac disease. In addition, we examine the effect of a gluten-free diet on the expression of these miRNAs in serum of CD patients. The expression pattern of miR-21 and miR-31 was estimated in serum of 25 untreated CD patients (recently diagnosed), 25 treated CD patients (on gluten-free diet) and 20 healthy controls using qRT-PCR. Our results demonstrated the significant up-regulation of microRNA-21 in the untreated celiac patients in comparison with the treated group and healthy controls. Moreover, miR-31 expression was significantly under-expressed in the untreated celiac patients in comparison with the treated group and healthy controls. Furthermore, the results showed that miR-21 expression level was significantly positively correlated with the tTG IgA auto-antibodies. In conclusion, circulating miRNA-21 and miRNA-31 could serve as potential non-invasive biomarkers for pediatric CD patients.

Microbial Biomarkers in Patients with Nonresponsive Celiac Disease.

In nonresponsive celiac disease (NRCD), the symptoms and duodenal damage persist despite a gluten-free diet. Celiac disease patients with persistent symptoms are found to have a dysbiotic microbiota. We thus hypothesized that increased seroreactivity to the serum gluten-sensitive microbial antibodies Saccharomyces cerevisiae (ASCA), Pseudomonas fluorescens-associated sequence (I2), and Bacteroides caccae TonB-linked outer membrane protein (OmpW) is associated with NRCD. ASCA, I2 and OmpW were measured in 20 seronegative CD patients with persistent villous damage despite strict dietary treatment (NRCD group). Fifty-eight responsive patients served as CD controls (55 on gluten-free treatment) and 80 blood donors as non-CD controls. At least one microbial marker was positive in 80% of NRCD patients, in 97% of untreated CD and 87% of treated CD patients, and in 44% of controls. NRCD patients had the highest frequency of ASCA positivity (65% vs 52, 20, and 0%, respectively) and also significantly higher ASCA IgA (median 14.5 U/ml) and IgG (32.5 U/ml) titers than treated CD patients (7.0 U/ml, 13.0 U/ml) and non-CD controls (4.5 U/ml, 5.8 U/ml). The frequencies of I2 and OmpW were lower in NRCD than in untreated CD (65% and 45% vs 86% and 59%, respectively), and I2 titers were higher in NRCD (median absorbance 0.76) and untreated (1.0) and treated (0.83) CD than controls (0.32). OmpW was elevated in untreated (1.1) and treated (0.94) CD patients compared with controls (0.79). Seropositivity and high titers of ASCA are associated with NRCD and might serve as an additional follow-up tool in CD.

Zmiany dotychczasowego stylu życia pod wpływem leczenia dietą bezglutenową w celiakii. Przyczynek do badań

Changes to past lif estyles as a result of no n-gluten dietary treatment in coeliac disease: A contribution to further researchStrict adherence to any elimination diet changes past styles of life of people. It refers especially to the ones who are obliged to introduce a diet because of a diagnosis of food-related illnesses, such as coeliac disease CD. The constraints perceived by the individuals on a dietary regimen may have a negative infl uence on their psychosocial functioning. The diffi culties are usually experienced in the situations connected with public consumption like social events and family gatherings.The article is an attempt to analyze how the implementation of a restrictive diet affects the past lifestyle of people diagnosed with CD. The only way of treatment of CD is a strict and lifelong elimination of gluten. The results presented are based on literature and a survey carried out on a group of forty people diagnosed with CD, recruited among the members of The Polish Association of People with Coeliac Disease and on a Gluten Free Diet GFD. The research tool was a socio-demographic and medical questionnaire of own authorship. The character of the survey was just preliminary as it is going to be followed by a further in-depth qualitative research in the future.The results of the analysis suggest that introducing a GFD may result in a worsening of psychosocial functioning of the suff erers, nevertheless some noticeable improvements in their somatic health. This explains why expanding the social awareness of the diffi culties experienced by people forced to undertake a GFD as a treatment is an important issue. It may contribute to the implementation of some good practices aimed at better quality of life of coeliac suff erers and elimination of barriers to regimen adherence they meet. It is of crucial importance as untreated CD may result in a gradual deterioration of their health status and occurrence of other serious diseases. Thus, supporting the suff erers of CD in adherence to dietary restrictions enhances their chances of maintaining an active style of life and more equal participation in social life.

Candidate Serum Markers in Early Crohn's Disease: Predictors of Disease Course.

More than half of patients with Crohn's disease [CD] develop disease complications requiring aggressive medical therapy or surgery over time. However, predicting disease course and treatment response remains difficult. We therefore identified distinctive serum analytes associated with disease activity and course in newly diagnosed, untreated patients at presentation and during their follow-up. In a pilot study, a multiplex immunoassay analysis on 36 markers was performed on serum from 20 CD patients at the time of primary diagnosis following endoscopic evaluation. The 12 most potent markers associated with disease activity, phenotype and course were analysed in a consecutive cohort of 66 CD patients at diagnosis and follow-up [n = 39]. A healthy control group [n = 20] was included as a reference. CD patients had higher baseline levels of sTNF-R2 [p = 0.001], sIL-2R [p = 0.0001], and MMP-1 [p = 0.001] compared with healthy controls. Serial measurements revealed that these three analytes dropped statistically significantly from baseline level during remission and were high during exacerbation. Great decline of sTNF-R1 levels was found during remission, with 6.7-fold lower levels than in healthy controls [p = 0.015]. Patients who did not respond to initial prednisone treatment had higher baseline levels of sTNF-R2 [p = 0.001]. Patients experiencing relapses during follow-up had lower baseline sTNF-R2 and VCAM levels compared with patients with long-lasting remission. In a large cohort of newly diagnosed untreated CD patients, we identified candidate serum markers [sTNF-R1, sTNF-R2, sIL-2R, and MMP-1] associated with disease activity. Furthermore, sTNF-R2 was associated with prednisone response and, together with VCAM, with long-lasting remission.

Top-down Infliximab Study in Kids with Crohn's disease (TISKids): an international multicentre randomised controlled trial

IntroductionCrohn's disease (CD) is a chronic inflammatory disease predominantly affecting the gastrointestinal tract. CD usually requires lifelong medication and is accompanied by severe complications, such as fistulae and strictures, resulting...

Hippocampal and cerebellar atrophy in patients with Cushing's disease.

OBJECT Cushing's disease (CD) may cause atrophy of different regions of the human brain, mostly affecting the hippocampus and the cerebellum. This study evaluates the use of 3-T MRI of newly diagnosed patients with CD to detect atrophic degeneration with voxel-based volumetry. METHODS Subjects with newly diagnosed, untreated CD were included and underwent 3-T MRI. Images were analyzed using a voxelwise statistical test to detect reduction of brain parenchyma. In addition, an atlas-based volumetric study for regions likely to be affected by CD was performed. RESULTS Nineteen patients with a mean disease duration of 24 months were included. Tumor markers included adrenocorticotropic hormone (median 17.5 pmol/L), cortisol (949.4 nmol/L), and dehydroepiandrosterone sulfate (5.4 μmol/L). The following values are expressed as the mean ± SD. The voxelwise statistical test revealed clusters of significantly reduced gray matter in the hippocampus and cerebellum, with volumes of 2.90 ± 0.26 ml (right hippocampus), 2.89 ± 0.28 ml (left hippocampus), 41.95 ± 4.67 ml (right cerebellar hemisphere), and 42.11 ± 4.59 ml (left cerebellar hemisphere). Healthy control volunteers showed volumes of 3.22 ± 0.25 ml for the right hippocampus, 3.23 ± 0.25 ml for the left hippocampus, 50.87 ± 4.23 ml for the right cerebellar hemisphere, and 50.42 ± 3.97 ml for the left cerebellar hemisphere. CONCLUSIONS Patients with untreated CD show significant reduction of gray matter in the cerebellum and hippocampus. These changes can be analyzed and objectified with the quantitative voxel-based method described in this study.

Differential accumulation and function of proinflammatory 6-sulfo LacNAc dendritic cells in lymph node and colon of Crohn's versus ulcerative colitis patients.

Human Slan DCs have been studied in patients with psoriasis, rheumatoid arthritis, cancer, and autoimmune diseases. In this study, we investigated the frequency, phenotype, and function of Slan DCs in blood, colon, as well as mLNs of patients with IBD. We first show that the frequency of circulating CD14(dull)Slan DCs was reduced in CD patients refractory to immunosuppressive drugs or TNF-α blockers relative to untreated CD, UC, and healthy subjects. In blood of CD patients, Slan DCs expressed CD172a, as detected by CD47 fusion protein binding, when compared with its lack of expression in control subjects. Next, we demonstrate that CD172a(+)Slan DCs that produced IL-1β and TNF-α accumulated in mLNs and colons of CD patients. The CD172a(+)Slan DCs up-regulated their expression of CD14 in CD tissues and the proinflammatory cytokines were produced in CD14(bright)CD172a(+)Slan DCs. By contrast, no difference was noted in the frequency of Slan DCs between inflamed, noninflamed colonic mucosa of UC patients and control, non-IBD donors. Finally, the percentage of cytokine-producing Slan DCs also augmented in response to TLR2 and NOD2 in in vitro stimulation in PBMCs of CD, but not UC, patients. In conclusion, we propose that proinflammatory CD14(bright)CD172a(+)Slan DCs are a distinguishing feature between CD and UC, as these cells accumulate uniquely in mLNs and colonic mucosa of CD patients. Thus, Slan DCs may contribute to CD immunopathogenesis.

Increased Mercury Levels in Patients with Celiac Disease following a Gluten-Free Regimen.

Background and Aim. Although mercury is involved in several immunological diseases, nothing is known about its implication in celiac disease. Our aim was to evaluate blood and urinary levels of mercury in celiac patients. Methods. We prospectively enrolled 30 celiac patients (20 treated with normal duodenal mucosa and 10 untreated with duodenal atrophy) and 20 healthy controls from the same geographic area. Blood and urinary mercury concentrations were measured by means of flow injection inductively coupled plasma mass spectrometry. Enrolled patients underwent dental chart for amalgam fillings and completed a food-frequency questionnaire to evaluate diet and fish intake. Results. Mercury blood/urinary levels were 2.4 ± 2.3/1.0 ± 1.4, 10.2 ± 6.7/2.2 ± 3.0 and 3.7 ± 2.7/1.3 ± 1.2 in untreated CD, treated CD, and healthy controls, respectively. Resulting mercury levels were significantly higher in celiac patients following a gluten-free diet. No differences were found regarding fish intake and number of amalgam fillings. No demographic or clinical data were significantly associated with mercury levels in biologic samples. Conclusion. Data demonstrate a fourfold increase of mercury blood levels in celiac patients following a gluten-free diet. Further studies are needed to clarify its role in celiac mechanism.

The burden and management of FXIII deficiency.

Factor XIII congenital deficiency (FXIII CD) is a serious bleeding disorder resulting in a lifelong bleeding tendency, defective wound healing and recurrent miscarriage. The aim of this study was to review available literature on the burden and management of FXIII CD. To this end, Medline, Embase and Cochrane databases were searched. In current literature, FXIII CD is described as one of the most severe forms of a congenital coagulation disorder, primarily due to a high risk of severe bleeding events. The published literature suggests that over 50% of untreated FXIII CD patients experience severe bleeding symptoms. Intracranial haemorrhage (ICH)--a major cause of death and morbidity--is reported to occur in up to one-third of patients. Nonetheless, data on the social and financial burden in patients with FXIII CD are sparse. Identified reports on the effectiveness and safety of recommended treatments support that patients with FXIII CD should receive prophylactic treatment as early as possible in their lives to prevent the occurrence of bleeds, including potentially life-threatening ICHs. In conclusion, limited data on the social and economic consequences related specifically to FXIII CD have been published to date. However, it is widely acknowledged that the high risk of severe bleeds and ICH results in a high level of burden in patients with bleeding disorders. To inform future clinical decision-making and reimbursement decisions, further research is required to gain insight in how specifically FXIII CD affects quality of life and to fully understand associated economic consequences.

An autoimmune disease refractory to immunosuppressive regimens: Celiac disease diagnosed long after liver transplantation

CD is defined as T-lymphocyte-mediated gluten sensitivity. Although CD is known to affect the small intestine, it is nonetheless a multisystem disorder. Liver involvement in CD may vary from isolated hypertransaminasemia to cirrhosis. Because CD is an inappropriate immune response to gluten proteins, strict gluten-free diet is the principal therapy, along with management of liver dysfunction. In patients who fail to respond to a gluten-free diet, immunosuppressive drugs may improve intestinal inflammatory activity in untreated CD. The present case report is of a 25-yr-old woman with diarrhea lasting several weeks. The patient had received a liver transplant 13yr earlier, and presented with cryptogenic cirrhosis diagnosed as CD. This appears to be the first case of its kind in which a pediatric long-term liver transplant patient presents with diarrhea eventually diagnosed as CD whose diet included gluten, and who was treated by an immunosuppressive drug regimen. Because of the normalization of CD-related antibodies in the post-transplantation period without gluten restriction, CD should be part of a list of diagnostic possibilities in liver transplant patients presenting with diarrhea of unknown etiology.

Prevalence and causes of abnormal liver function in patients with coeliac disease

Coeliac disease patients frequently display mild elevation of liver enzymes and this abnormality usually normalizes after gluten-free diet. To investigate the cause and prevalence of altered liver function tests in coeliac patients, basally and after 1 year of gluten-free diet. Data from 245 untreated CD patients (196 women and 49 men, age range 15-80 years) were retrospectively analysed and the liver function tests before and after diet, as well as associated liver pathologies, were assessed. Overall, 43/245 (17.5%) patients had elevated values of one or both aminotransferases; the elevation was mild (<5 times the upper reference limit) in 41 (95%) and marked (>10 times the upper reference limit) in the remaining 2 (5%) patients. After 1 year of gluten-free diet, aminotransferase levels normalized in all but four patients with HCV infection or primary biliary cirrhosis. In coeliac patients, hypertransaminaseaemia at diagnosis and the lack of normalization of liver enzymes after 12 months of diet suggest coexisting liver disease. In such instance, further evaluation is recommended to exclude the liver disease. Early recognition and treatment of coeliac disease in patients affected by liver disease are important to improve the liver function and prevent complications.

Celiac Disease: Association with Iron Deficiency in Caucasians but Not in Non-Caucasians.

AbstractAbstract 2095Celiac disease (CD) is an increasingly recognized disorder in Caucasian populations of European origin. Little is known about its prevalence in non-Caucasians. While CD is thought to be a cause of iron deficiency anemia, the extent to which CD contributes to iron deficiency in Caucasians and especially non-Caucasians is unknown. Iron deficiency is one of the most common nutritional deficiencies in both the developed world and in developing countries. Thus, it is important to know the prevalence of CD in different populations and in iron-deficient and iron-replete persons. To answer these questions, we tested serum collected from Caucasian and non-Caucasian men aged ≥ 25 y and women ≥ 50 y in the Hemochromatosis and Iron Overload Screening (HEIRS) Study. In the HEIRS Study, 101,168 participants were screened with serum biochemical tests of iron status, which not only detected participants with iron overload but also identified a unique multiethnic population of participants with iron deficiency. We hypothesized that CD is more common in those with iron deficiency than in iron-replete individuals. We also examined the difference in frequency of CD between Caucasians and non-Caucasians with iron deficiency.Cases with iron deficiency (defined as serum ferritin ≤ 12 μg/L [cases]) and iron-replete controls (serum ferritin > 100 μg/L in men, serum ferritin > 50 μg/L in women) were further evaluated by using a sequential serological testing scheme whereby all samples were tested with an ELISA for human recombinant tissue transglutaminase IgA antibodies, and positive values were confirmed by endomysial antibodies. Those positive for both tests were considered double positives and were presumed to have untreated CD. Those positive for tissue transglutaminase IgA antibodies but not for endomysial antibodies were termed single positives and were considered indeterminate and excluded from analysis. We further hypothesized that low serum ferritin and an appropriate human leukocyte antigen (HLA) variant, may be predictive of CD. We used SNP-based analysis to determine HLA genotype and DQ8, DQ2.2 or DQ4, and DQ2.5 risk variants. Fisher’s exact test was used to examine the association between iron−deficient case and control status and the presence of celiac disease. Log-binomial regression was applied to estimate the odds of celiac disease in iron-deficient cases relative to that of controls.A total of 1713 subjects were tested for tissue transglutaminase IgA antibodies. Participants included 1100 Caucasians, 221 African Americans, 153 Asians, and 239 Hispanics. Fourteen of 571 iron-deficient cases were positive for the double serology compared to just one of 1142 controls. All of the seropositive tests were seen in Caucasians and none in the non-Caucasians. Excluding data from participants with indeterminate serological screen results (6 Caucasians, 4 non-Caucasians), we found that CD occurred in 14 of 567 cases (2.5%) and in only 1 of 1136 (0.1%) controls (Fisher’s exact test, p=1.92 10−6). CD was more common in Caucasian cases (14 of 363, 4%) than in non-Caucasian cases (0 of 204, p=0.003). Only one Caucasian control and none of the non-Caucasian controls had CD. The odds of CD in individuals with iron deficiency was 28 (3.7, 212.8) times that in controls. Thirteen of 14 iron-deficient cases with CD carried the DQ2.5 variant of the HLA genotype. Presence of DQ2.5 was highly significantly associated with celiac disease status in iron-deficient cases compared to controls (Fisher’s exact test, p = 7.183 × 10−8).The results indicate that CD is a small but significant contributor to iron deficiency in Caucasians. CD is very rare in other races, even among individuals with features frequently seen in CD, such as iron deficiency. CD is also rare in Caucasians who are iron replete. CD testing should be considered for adult Caucasian males or post-menopausal females having iron deficiency without evidence of other etiologies such as gastrointestinal blood loss. Patients identified with CD may benefit from appropriate treatment. Disclosures:No relevant conflicts of interest to declare.

TH1 and TH17 interactions in untreated inflamed mucosa of inflammatory bowel disease, and their potential to mediate the inflammation

BackgroundCrohn’s disease (CD) and ulcerative colitis (UC) have been associated with a T helper1 (TH1) and a TH2 cytokine profile, respectively. Recently, a TH17 lineage has been introduced, but their role in the inflammation of CD and UC is not fully understood. AimTo characterize the cytokines directing the TH17 cells and their interactions with TH1 cells in the mucosa of untreated patients with CD and UC. MethodSeventy-nine patients with untreated UC, 32 patients with untreated CD and 23 controls with no signs of colon disease were included in the study. Clinical indices for ulcerative colitis (UCDAI) and Crohn’s disease (CDAI) were assessed. Biopsies for measurements of interleukin (IL)-17A, IL-23, IL-6, transforming growth factor-beta (TGF-β), interferon-gamma (IFN-γ), mRNA levels as well as immunohistochemical (IHC) analyses were performed. ResultsThe gene expression for all cytokines in UC and for all cytokines except for TGF-β in CD were significantly increased compared with the controls. The immunohistochemical analysis showed significantly increased number of IL-17A positive cells in lamina propria and epithelium of both UC and CD compared to controls. The levels of IL-17A and IL-23 mRNA were significantly higher in UC than in CD while the levels of IL-6 were significantly higher in CD compared with UC. The levels of IL-17A, IL-6 and IL-23 mRNA were associated with the disease activity score in both UC and CD. IFN-γ was associated with the disease activity in UC, but did not reach significant level in CD. ConclusionIncreased levels of IL-17A and IL-23 were found in both UC and CD compared to controls. Association to the grade of inflammation and clinical activity was also observed. IL-17A and IL-23 were significantly higher in UC than in CD. TH1 and TH17 cytokines seem to act synergistically in inflammatory bowel disease (IBD) with no apparent polarization between UC and CD.

Differences of small intestinal bacteria populations in adults and children with/without celiac disease: Effect of age, gluten diet, and disease

Scientific evidence has revealed microecological changes in the intestinal tract of celiac infants. The objective of this work is the study of bacterial differences in the upper small intestine in both adults (healthy, untreated celiac disease [CD], and CD treated with a gluten-free diet) and children (healthy and untreated CD). Intestinal bacterial communities were identified by 16S rRNA gene sequencing of DNA extracted from duodenal biopsies. Analysis of the sequences from adults and children showed that this niche was colonized by bacteria affiliated mainly with three phyla: Firmicutes, Proteobacteria, and Bacteroidetes. In total, 89 different genera were identified in adults and 46 in children. Bacterial richness was significantly lower in the children than in the adults. A global principal component analysis of the bacterial communities of both healthy and untreated CD patient groups (including both children and adults) revealed a strong effect of age in principal component 1--clustering all adults and children separately--and a possible effect of the disease in adults with untreated patients clustering separately. There are bacterial differences in the upper small intestine between untreated children CD patients and untreated CD adults due to age. There are bacterial differences in the upper small bacteria microbiota between treated and untreated CD adults due to treatment with a gluten-free diet.

785 Small for Gestational Age Newborns (SGA) and Coeliac Disease: A Casecontrol Study

A SGA birth could be a symptom of undiagnosed CD in mother. Early diagnosis and treatment may avoid damages (1). Aim: To determine the prevalence of untreated CD among SGA mothers (SgaM). Methods: From September 2007 to October 2009, SgaM (cases) and Nga mothers (NgaM) were enrolled. Exclusion criteria: twin birth, artificial insemination. Blood samples were taken (5 cc) and antihuman IgA and IgG classes antitissue transglutaminase antibodies (IgA and IgG anti-tTg ab) were tested by ELISA commercial kit (Eurospital, Trieste, Italy); total IgA ab were tested. Statistical analysis: Fisher exact test, Odd ratio (OR). Results: 193 SgaM (mean age 31,7 y) and 230 NgaM (mean age 31,1y) were enrolled. SGA newborns were like NGA newborns except for the for the body weight at birth (1977 ± 584,5g vs. 2830 ± 701,6g; p< 0,05). SgaM had an higher risk of spontaneous abortions (OR = 1,2). In studied population we found 3 celiac mothers (0.7%) at gluten free diet (GFD); in 3 /423 (0,7%) woman IgA and IgG antitTg ab were positive:1/193 (0,51 %) was SgaM and 2/230 (0,86 %) were NgaM (p=ns). In the new three cases an intestinal biopsy showed subtotal villous atrophy (Marsh 2) and HLA determination showed DQ2 positivity. Conclusions: Undiagnosed CD doesn't seem more frequent among SGA mothers than in the general population. However, screening for CD during pregnancy could lead to the effective strategies for the prevention of such disease.

Synthesis and biological evaluation of novel spiro 6-methoxytetralin-1,3′-pyrrolidine based organoselenocyanates against cadmium-induced oxidative and hepatic damage in mice

A series of novel organoselenocyanate compounds ( 6a– d) having spiro[tetralin-1,3′-pyrrolidine] moiety were synthesized. The compounds were evaluated for their inhibitory activity against cadmium- (Cd) induced toxicity in Swiss Albino mice. All the compounds ( 6a– d) inhibited the level of lipid peroxidation (LPO) and upregulated the activity of glutathione-S-transferase (GST), superoxide dismutase (SOD), catalase (CAT) and reduced glutathione (GSH) levels in treatment group in comparison to the untreated Cd control group. Serum transaminase activities, e.g., alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were also significantly lowered in the compound-treated mice. Elongation of the alkyl chain length bearing the selenocyanate (SeCN) active group enhanced the potency of the compounds, 6d being the most active one ( 6d > 6c > 6b > 6a).