Prevalence of celiac disease in Iranian patients with rheumatologic disorders

Aim: Patients with Systemic Lupus Erythematosus [SLE], Rheumatoid Arthritis [RA], and Fibromyalgia [FM] may have underlying non-diagnosed celiac disease [CD]

Background: The aim of this study was to determine the prevalence of CD in patients with these underlying diseases in Iran

Methods: This cross-sectional study was performed among 300 consecutive patients with SLE, RA, and FM [each group 100 patients] since 2015 to 2017. The blood samples were collected and serum IgA anti-tissue trans-glutaminase [Anti-tTG] level was assessed for all patients. The seropositive patients underwent endoscopy and duodenal/jejunal biopsy according to the Marsh classification

Results: Out of 300 investigated patients with mean age of 41.2 years old, 92% of patients with SLE, RA and fibromyalgia were women. Among 100 patients with SLE, only 1 subject [1%], out of 100 patients with RA 3 subjects [3%], and none of the patients with fibromyalgia were seropositive for CD [with overall prevalence 1.4]. All four patients were female and categorized as Marsh III

Conclusion: The results of the study indicated that patients with lupus have the same prevalence, but subjects with RA had three times higher prevalence rate than normal population for CD. Therefore, CD investigation in these individuals can improve their quality of life

rapid and sensitive assay to identify HLA-DQ2/8 risk alleles for celiac disease using real-time PCR method

Aim: To perform a simple, rapid and sensitive Real-time PCR based SYBR Green method to determine the human leukocyte antigen [HLA]-DQ 2/8 alleles in celiac disease [CD] patients

Background: Many molecular techniques are available to determine the HLA-DQ2 and DQ8 alleles, but they are too expensive and have many steps that make them difficult to use

Methods: To determine the HLA-DQ 2/8 alleles we have developed a new real-time PCR assay, using SYBR Green technique with melting curve analysis on genomic DNA isolated from 75 CD patients and 94 healthy controls. The specific primers to examine HLADQA1* 05, HLA-DQB1*02 and HLA-DQB1*0302 alleles were used and results were compared with commercially available kits

Results: Using this method, the presence of HLA-DQ2 and HLA-DQ8 alleles were determined with sensitivity and specificity 80% and 100% respectively and compared to low resolution commercially available kits, the results of this method were more efficient. The frequency of DQ2 and DQ8 in patients was 76% and 29%, respectively and overall 96% of patients were carries DQ2 and/or DQ8 alleles

Conclusion: The result of this study showed that Real-time PCR using SYBR Green method with melting curve analysis has good efficiency to identify the HLA-DQ2/8 risk alleles

Probiotics and their role in gastrointestinal cancers prevention and treatment; an overview

Cancers of the gastrointestinal [GI] track are a serious global health problem. The human GI tract is home to trillions of microorganisms that known as gut microbiota and have established a symbiotic relationship with the host. The human intestinal microbiota plays an important role in the development of the gut immune system, metabolism, nutrition absorption, production of short-chain fatty acids and essential vitamins, resistance to pathogenic microorganisms, and modulates a normal immunological response. Microbiota imbalance has been involved in many disorders including inflammatory bowel disease, obesity, asthma, psychiatric illnesses, and cancers. Oral administration of probiotics seems to play a protective role against cancer development as a kind of functional foods. Moreover, clinical application of probiotics has shown that some probiotic strains can reduce the incidence of post-operative inflammation in cancer patients. In the present narrative review, we carried out update knowledge on probiotic effects and underlying mechanism to GI cancers. Currently, it is accept that most commercial probiotic products are generally safe and can used as a supplement for cancer prevention and treatment. Nevertheless, well-designed, randomized, double blind, placebocontrolled human studies are required to gain the acceptance of the potential probiotics as an alternative therapy for cancer control.

Comparative study of gastric cancer and chronic gastritis via network analysis

Aim: In this study the significant differentially expressed genes [DEGs] related to gastric cancer [GC] and chronic gastritis were screened to introduce common and distinctive genes between the two diseases

Background: Diagnosis of gastric cancer as a mortal disease and chronic gastritis the stomach disorder which can be considered as risk factor of GCs required safe and effective molecular biomarkers

Methods: Microarray profiles were downloaded from Gene Expression Omnibus [GEO] and analyzed via GEO2R. The candidate DEGs plus relevant genes from STRING database were interacted by Cytoscape software version 3.6.0 the central nodes were determined and analyzed

Results: JUN, GAPDH, FOS, TP53, PRDM10, VEGFA, and CREB1 as central nodes and TFF1 and ERG1 as the top changed expressed genes were determined as critical nodes related to gastric cancer. GAPDH, PRDM10, TP53, JUN, AKT1, EGFR, MAPK1, EGF, DECR1, and MYC were identified as common remarkable genes between GC and chronic gastritis

Conclusion: Identification of distinctive and common genes between GC and chronic gastritis can be useful in the early stage detection of disease and reducing risk of GCs

Introducing crucial protein panel of gastric adenocarcinoma disease

Aim: Since interactome analysis of diseases can provide candidate biomarker panel related to the diseases, in this research, proteinprotein interaction [PPI] network analysis is used to introduce the involved crucial proteins in Gastric adenocarcinoma [GA]

Background: Gastric adenocarcinoma [GA] is the most common type of stomach cancer. There is no efficient diagnostic molecular method for GA

Methods: Applying Cytoscape software 3.4.0 and String Database, the PPI network was constructed for 200 genes. Based on centrality parameters, the critical nodes were screened. Gene ontology of the key proteins for pathway analysis and molecular function processing were done and the highlighted pathways and activities were discussed

Results: Among 200 initial genes, 141 genes were included in a main connected network. Seven crucial proteins, including tumor protein p53, epidermal growth factor receptor, albumin, v-erb-b2 erythroblastic leukemia viral oncogene homolog 2, neuro/glioblastoma derived oncogene homolog [avian], v-akt murine thymoma viral oncogene homolog 1, v-src sarcoma [Schmidt-Ruppin A-2] viral oncogene homolog [avian] and catenin [cadherin-associated protein], beta 1, 88kDa, and Myogenic differentiation 1, were introduced as key nodes of the network. These identified proteins are mostly involved in pathways and activities related to cancer

Conclusion: In conclusion, the finding is corresponding to the significant roles of these introduced proteins in GA disease. This protein panel may be a useful probe in the management of GA

[Refractory celiac disease; diagnosis, treatment and clinical manifestations]

Celiac disease as an autoimmune disease is predisposes in genetically susceptible subjects due to the consumption of wheat and other grains containing gluten and as a result of immunological responses, villous atrophy, mucosal hyperplasia, and lymphocytic infiltration will be occurred. The only treatment is a lifelong gluten-free diet. Most patients with celiac disease respond to gluten-free diet [GFD]. But in a small percentage of patients, despite full compliance with gluten-free diet, symptoms and mucosal atrophy are remains. When other causes of mucosal atrophy are rejected, the diagnosis of refractory celiac disease [RCD] is suggested. Based on the abnormality in population of intraepithelial lymphocytes [IEL], RCD is divided into two types 1; [RCD I] and type 2 [RCDII]. Prognosis, clinical symptoms and endoscopic findings of RCD I are better and milder than the RCD II. Treatment of RCD I is based on immunosuppressive therapy and RCD II is mostly based on nutritional support and chemotherapeutic agents. In this review the clinical characteristics, diagnostic and treatment approach of RCD will be reviewed

Economic burden made celiac disease an expensive and challenging condition for Iranian patients

Aim: The aim of this study was to estimate the economic burden of celiac disease [CD] in Iran

Background: The assessment of burden of CD has become an important primary or secondary outcome measure in clinical and epidemiologic studies

Methods: Information regarding medical costs and gluten free diet [GFD] costs were gathered using questionnaire and checklists offered to the selected patients with CD. The data included the direct medical cost [including Doctor Visit, hospitalization, clinical test examinations, endoscopies, etc.], GFD cost and loss productivity cost [as the indirect cost] for CD patient were estimated. The factors used for cost estimation included frequency of health resource utilization and gluten free diet basket. Purchasing Power Parity Dollar [PPP dollars] was used in order to make inter-country comparisons

Results: Total of 213 celiac patients entered to this study. The mean [standard deviation] of total cost per patient per year was 3377 [1853] PPP dollars. This total cost including direct medical cost, GFD costs and loss productivity cost per patients per year. Also the mean and standard deviation of medical cost and GFD cost were 195 [128] PPP dollars and 932 [734] PPP dollars respectively. The total costs of CD were significantly higher for male. Also GFD cost and total cost were higher for unmarried patients

Conclusion: In conclusion, our estimation of CD economic burden is indicating that CD patients face substantial expense that might not be affordable for a good number of these patients. The estimated economic burden may put these patients at high risk for dietary neglect resulting in increasing the risk of long term complications

Celiac disease and hepatitis C relationships in transcriptional regulatory networks

Aim: we mainly aimed to elucidate potential comorbidities between celiac disease and hepatitis c by means of data and network analysis approaches

Background: understanding the association among the disorders evidently has important impact on the diagnosis and therapeutic approaches. Celiac disease is the most challenging, common types of autoimmune disorders. On the other hand, hepatitis c virus genome products like some proteins are supposed to be resemble to gliadin types that in turn activates gluten intolerance in people with inclined to gluten susceptibilities. Moreover, a firm support of association between chronic hepatitis and celiac disease remains largely unclear. Henceforth exploring cross-talk among these diseases will apparently lead to the promising discoveries concerning important genes and regulators

Methods: 321 and 1032 genes associated with celiac disease and hepatitis c retrieved from DisGeNET were subjected to build a gene regulatory network. Afterward a network-driven integrative analysis was performed to exploring prognosticates genes and related pathways

Results: 105 common genes between these diseases included 11 transcription factors were identified as hallmark molecules where by further screening enriched in biological GO terms and pathways chiefly in immune systems and signaling pathways such as chemokines, cytokines and interleukins

Conclusion: in silico data analysis approaches indicated that the identified selected combinations of genes covered a wide range of known functions triggering the inflammation implicated in these diseases

Syphacia obvelata: A New Hope to Induction of Intestinal Immunological Tolerance in C57BL/6 Mice

The ability of nematodes to manipulate the immune system of their host towards a Th2 and T regulatory responses has been proposed to suppress the inflammatory response. Clinical trials have proposed a useful effect of helminth infections on improvement of inflammatory disorders. In this study, we investigated the immunomodulatory effect of Syphacia obvelata infection to induce intestinal tolerance in C57BL/6 mice. Mice were infected through the cagemates with self-infected BALB/c mice. Four weeks post-infection, expression levels of IFN-γ, TNF-α, IL-17, and IL-10 were assessed in the supernatant of mesenteric lymph node (MLN) culture. Foxp3⁺Treg were measured in MLN cells by flow cytometry. In the S. obvelata-infected group, the percentage of Tregs (5.2±0.4) was significantly higher than the control (3.6±0.5) (P<0.05). The levels of IL-10 (55.3±2.2 vs 35.2±3.2), IL-17 (52.9±3.8 vs 41±1.8), IFN-γ (44.8±4.8 vs 22.3±2.3) and TNF-α (71.1±5.8 vs 60.1±3.3) were significantly increased in infected mice compared to the control group (P<0.05). The above results showed the potential effects of S. obvelata to induce intestinal tolerance. Therefore, it seems that S. obvelata may increase the immunological suppressive function in the intestinal tract.

Pathological and clinical correlation between celiac disease and pathological and clinical correlation between celiac disease andpathological and clinical correlation between celiac disease and helicobacter pylori infection; a review of controversial rep

There are overwhelming reports and descriptions about celiac associated disorders. Although there is a clear genetic association between celiac disease [CD] and some gastrointestinal disorders, there are controversial reports claiming an association between CD and Helicobacter pylori [H. pylori] infection. Different studies indicated the possible association between lymphocytic gastritis and both CD and H. pylori infection, although this evidence is not consistently accepted. Also it was shown that an increase in intraepithelial lymphocytes count is associated with both H. pylori infection and celiac disease. Therefore the following questions may raise: how far is this infection actually related to CD?, which are the underlying patho-mechanisms for these associations? what are the clinical implications? what is the management? and what would be the role of gluten free diet in treating these conditions? PubMed [PubMed Central], Ovid, ISI of web knowledge, and Google scholar were searched for full text articles published between 1985 and 2015. The associated keywords were used, and papers described particularly the impact of pathological and clinical correlation between CD and H. pylori infection were identified. In this review we tried to answer the above questions and discussed some of the recent developments in the pathological and clinical aspects of CD and H. pylori infection

likelihood ratio and frequency of DQ2/DQ8 haplotypes in Iranian patients with celiac disease

Aim: The aim of this study was to evaluate the likelihood ratio and frequency of DQ2 and DQ8 in Iranian patients with celiac disease [CD]

Background: The HLA DQ2 and HLA DQ8 are the important mediators in the development of celiac disease. A few studies evaluated the frequency of HLA DQ2 and HLA DQ8 haplotypes among the Iranian population with low sample size

Patients and methods: In this cross-sectional study, to predict HLA-DQ2 and DQ8 haplotypes, 141[73 male, 78 female] confirmed CD patients compared to 151 healthy controls were enrolled into this study during 2013-2014. HLA DQ2/ DQ8 haplotypes was determined in cases and controls using PCR-SSP technique

Results: DQ2 and DQ8 were positive in 80% [n=111] and 49% [n= 69] of CD patients and 36% [n=61] and 13% [n=21] of control group respectively. Moreover, 32% [n=45] of CD patients and 5.3% [n=8] of the control group were carrier of both haplotypes. In the case group about one-third of patients [32.2%] were positive for carrying both DQ2 and DQ8 heterodimers while only 5.3% [n=8] of the control group were carrier. In addition, the positive likelihood ratio of DQ2 and DQ8 were 1.74 [CI: 1.4- 2.1], and 2.6 [CI: 1.8- 2.7], respectively

Conclusion: The result of this study showed that the frequency of DQ8 among our population is higher than those reported by European countries, but it is close to those founded in South America and Middle East. This result suggests that the higher prevalence of HLA DQ8 pattern in Iranian CD patients is similar to non-European patients

experimental model of colitis induced by dextran sulfate sodium from acute progresses to chronicity in C57BL/6: correlation between conditions of mice and the environment

Aim: To induce acute colitis progresses to chronicity in C57BL/6 mice by dextran sulfate sodium

Background: Murine models are essential tools to understand IBD pathogenesis. Among different types of chemically induced colitis models, the dextran sulfate sodium [DSS]-induced colitis model is the most common model of IBD, due to its simplicity

Patients and methods: Male C57BL/6 mice 6-8 weeks old, were collected and matched by age with controls. C57BL/6 mice treated with 2 cycles of 3.5% DSS for 4 days and 4 days of pure water between each cycle. After that, mice were sacrificed and the entire colon was removed. Small sections of the colon were fixed in formaldehyde, embedded in paraffin and sectioned with a microtome. Sections were stained with hematoxylin eosin to analyses the degree of inflammation

Results: After the first cycle oral administration of DSS, mice with severe and visible rectal bleeding and diarrhea entered into the acute phase. After day 4-5, bleeding and diarrhea were improved and mice entered into the chronic phase with peak levels of weight loss. Macroscopically, the inflammation was predominantly located in the distal colon. Microscopically, examination of the distal colon sections showed a decrease number of goblet cells, loss of crypts, signs of surface epithelial regeneration and moderate to severe infiltration of inflammatory cells in the mucosa

Conclusion: In order to achieve an experimental colitis model, our protocol is recommended for future therapies in IBD experimental modeling

Protein-protein interaction network of celiac disease

Aim: The aim of this study is to investigate the Protein-Protein Interaction Network of Celiac Disease

Background: Celiac disease [CD] is an autoimmune disease with susceptibility of individuals to gluten of wheat, rye andbarley. Understanding the molecular mechanisms and involved pathway may lead to the development of drug targetdiscovery. The protein interaction network is one of the supportive fields to discover the pathogenesis biomarkers for celiacdisease

Material and Methods: In the present study, we collected the articles that focused on the proteomic data in celiac disease.According to the gene expression investigations of these articles, 31 candidate proteins were selected for this study. Thenetworks of related differentially expressed protein were explored using Cytoscape 3.3 and the PPI analysis methods suchas MCODE and ClueGO

Results: According to the network analysis Ubiquitin C, Heat shock protein 90kDa alpha [cytosolic and Grp94]; class A, Band 1 member, Heat shock 70kDa protein, and protein 5 [glucose-regulated protein, 78kDa], T-complex, Chaperon incontaining TCP1; subunit 7 [beta] and subunit 4 [delta] and subunit 2 [beta], have been introduced as hub-bottlnecksproteins. HSP90AA1, MKKS, EZR, HSPA14, APOB and CAD have been determined as seed proteins

Conclusion: Chaperons have a bold presentation in curtail area in network therefore these key proteins beside the other hubbottlneckproteins may be a suitable candidates biomarker panel for diagnosis, prognosis and treatment processes in celiac disease

H.pylori associated with iron deficiency anemia even in celiac disease patients; strongly evidence based but weakly reflected in practice

Inflammation can lead to malabsorption of important micronutrients such as iron. Malabsorption and nutritional deficiency can be caused by a variety of pathological and environmental factors causing a range of other symptoms commonly caused by both H. pylori infection and coeliac disease [CD]. National guidelines suggest the routine taking of duodenal biopsies to exclude CD when investigating patients for iron deficiency anemia [IDA]. Studies suggest that in absence of positive antibodies, IDA is rarely caused by CD. Recent British Society of Gastroenterology guidelines discourage the routine duodenal biopsies in low risk cases but despite this guidance, taking duodenal biopsies for IDA is a common practice. Many studies have reported that H. pylori infection is associated with IDA even in patients with CD. In countries with low H. pylori prevalence we still detect more H. pylori than CD standing behind IDA. Despite the strong association between IDA and H. pylori, taking biopsies to diagnose H. pylori infection is not usually a routine part of the diagnostic workup to identify the etiology of IDA. In this review we will discuss the impact of H. pylori in IDA and highlight the possible gaps in identifying the IDA etiology

importance of histologic parameters of lacteal involvement in cases of canine lymphoplasmacytic enteritis

The most frequent form of inflammatory bowel disease [IBD] in dogs is represented histologically, by lymphoplasmacytic enteritis [LPE], a histological category, often associated with other morphologic alterations including lymphangiectasia [LE]. However, literature data on this latter topic are quite scarce and have mostly been obtained in single reports or in small series. We evaluated some morphologic parameters of intestinal villi and lacteals in a large cohort of dogs, and correlated them with serum albumin and cholesterol values. We investigated 136 dogs [94 with LPE, and 42 with gastrointestinal problems different from IBD] and analyzed their clinical, laboratory [albumin and cholesterol values], endoscopic, and histologic variables. The LPE group showed significantly impaired clinical, laboratory, endoscopic, and histologic variables compared to controls. Affected dogs showed significant correlations between canine inflammatory bowel disease activity index [CIBDAI] scores and endoscopic and histologic variables. Moreover, the grade of hematologic changes were strongly related to the intestinal histologic variables, in particular those concerning villous and lacteals morphology. Dogs with LPE had intestinal histologic abnormalities [height, width, height/width ratio, calculated for both villi and lacteals], whose degree correlated with the severity of hypoalbuminemia and hypocholesterolemia. Evaluation of endoscopic and histologic variables in association to the clinical findings may reveal useful insights for the pathogenesis of LPE and, hopefully, might lead to more targeted therapeutic approaches

Post gastroenteritis gluten intolerance

The spectrum of gluten related disorder might be much broader than currently believed. It is unknown why non-coeliac gluten sensitivity affects individuals at different ages. It is quite possible that triggering factors like infection might play an essential role in manifestation of this disorder. Similar to secondary lactose intolerance, gluten intolerance might be a common occurrence behind persistent symptoms after gastroenteritis. Presenting symptoms may depend on etiological factors and the affected portion of gastrointestinal [GI] anatomy. Therefore symptoms might be related to the upper GI tract like functional dyspepsia, or the lower GI tract like diarrhoea and constipation or a combination of both as in our patients. This case highlights that intolerance to gluten may develop in people who experience gastroenteritis and there is potential of at least partial recovery from this condition with elimination of lactose and gluten. Clinical recovery with a concomitant gluten and lactose [mainly milk] free diet over a period of time might be an effective strategy in treating these patients

relationship between intestinal parasites and some immune-mediated intestinal conditions

Over the last decades, the incidence of infestation by minor parasites has decreased in developed countries. Infectious agents can also suppress autoimmune and allergic disorders. Some investigations show that various protozoa and helminthes are connected with the main immune-mediated intestinal conditions including celiac disease [CD], inflammatory bowel diseases [IBD] and irritable bowel syndrome [IBS]. Celiac disease is a digestive and autoimmune disorder that can damage the small intestine and characterized by a multitude gastrointestinal [GI] and extra GI symptoms. IBD [including ulcerative colitis and Crohn's disease] is a group of inflammatory conditions of the small intestine and colon. The etiology of IBD is unknown, but it may be related to instability in the intestinal microflora that leading to an immoderate inflammatory response to commensal microbiota. Irritable bowel syndrome [IBS] is a common, long-term condition of the digestive system. Bloating, diarrhoea and/or constipation are nonspecific symptoms of IBS. Various studies have shown that some intestinal parasites can effect on immune system of infected hosts and in some cases, they are able to modify and change the host's immune responses, particularly in autoimmune disorders like celiac disease and IBD. The main objective of this review is to investigate the relationship between intestinal parasites and different inflammatory bowel disorders

Echinococcus granulosus genotypes in Iran

Hydatidosis, caused by Echinococcus granulosus is one of the most important zoonotic diseases, throughout most parts of the world. Hydatidosis is endemic in Iran and responsible for approximately 1% of admission to surgical wards. There are extensive genetic variations within E. granulosus and 10 different genotypes [G1-G10] within this parasite have been reported. Identification of strains is important for improvement of control and prevention of the disease. No new review article presented the situation of Echinococcus granulosus genotypes in Iran in the recent years; therefore in this paper we reviewed the different studies regarding Echinococcus granulosus genotypes in Iran.