New entity of adult ultra-short coeliac disease: the first international cohort and case-control study.

BACKGROUND: Ultra-short coeliac disease (USCD) is defined as villous atrophy only present in the duodenal bulb (D1) with concurrent positive coeliac serology. We present the first, multicentre, international study of patients with USCD. METHODS: Patients with USCD were identified from 10 tertiary hospitals (6 from Europe, 2 from Asia, 1 from North America and 1 from Australasia) and compared with age-matched and sex-matched patients with conventional coeliac disease. FINDINGS: Patients with USCD (n=137, median age 27 years, IQR 21-43 years; 73% female) were younger than those with conventional coeliac disease (27 vs 38 years, respectively, p<0.001). Immunoglobulin A-tissue transglutaminase (IgA-tTG) titres at index gastroscopy were lower in patients with USCD versus conventional coeliac disease (1.8×upper limit of normal (ULN) (IQR 1.1-5.9) vs 12.6×ULN (IQR 3.3-18.3), p<0.001).Patients with USCD had the same number of symptoms overall (median 3 (IQR 2-4) vs 3 (IQR 1-4), p=0.875). Patients with USCD experienced less iron deficiency (41.8% vs 22.4%, p=0.006).Both USCD and conventional coeliac disease had the same intraepithelial lymphocytes immunophenotype staining pattern; positive for CD3 and CD8, but not CD4.At follow-up having commenced a gluten-free diet (GFD) (median of 1181 days IQR: 440-2160 days) both USCD and the age-matched and sex-matched controls experienced a similar reduction in IgA-tTG titres (0.5 ULN (IQR 0.2-1.4) vs 0.7 ULN (IQR 0.2-2.6), p=0.312). 95.7% of patients with USCD reported a clinical improvement in their symptoms. INTERPRETATION: Patients with USCD are younger, have a similar symptomatic burden and benefit from a GFD. This study endorses the recommendation of D1 sampling as part of the endoscopic coeliac disease diagnostic workup.

Leveraging machine learning for early recurrence prediction in hepatocellular carcinoma: A step towards precision medicine.

The high rate of early recurrence in hepatocellular carcinoma (HCC) post curative surgical intervention poses a substantial clinical hurdle, impacting patient outcomes and complicating postoperative management. The advent of machine learning provides a unique opportunity to harness vast datasets, identifying subtle patterns and factors that elude conventional prognostic methods. Machine learning models, equipped with the ability to analyse intricate relationships within datasets, have shown promise in predicting outcomes in various medical disciplines. In the context of HCC, the application of machine learning to predict early recurrence holds potential for personalized postoperative care strategies. This editorial comments on the study carried out exploring the merits and efficacy of random survival forests (RSF) in identifying significant risk factors for recurrence, stratifying patients at low and high risk of HCC recurrence and comparing this to traditional COX proportional hazard models (CPH). In doing so, the study demonstrated that the RSF models are superior to traditional CPH models in predicting recurrence of HCC and represent a giant leap towards precision medicine.

Metabolomics and lipidomics signature in celiac disease: a narrative review.

Celiac disease (CD) is a chronic immune-mediated inflammatory disease of the small intestine caused by aberrant immune responses to consumed gluten proteins. CD is diagnosed by a combination of the patients reported symptoms, serologic and endoscopic biopsy evaluation of the small intestine; and adherence to a strict gluten-free diet (GFD) is considered the only available therapeutic approach for this disorder. Novel approaches need to be considered for finding new biomarkers to help this disorder diagnosis and finding a new alternative therapeutic method for this group of patients. Metabolomics and lipidomics are powerful tools to provide highly accurate and sensitive biomarkers. Previous studies indicated a metabolic fingerprint for CD deriving from alterations in gut microflora or intestinal permeability, malabsorption, and energy metabolism. Moreover, since CD is characterized by increased intestinal permeability and due to the importance of membrane lipid components in controlling barrier integrity, conducting lipidomics studies in this disorder is of great importance. In the current study, we tried to provide a critical overview of metabolomic and lipidomic changes in CD.

Diagnosis of Seronegative and Ultrashort Celiac Disease.

In its conventional form, celiac disease (CeD) is characterized by both positive serology and flat villi in the duodenum, and is well known by gastroenterologists and general practitioners. The aim of this review was to shed light on 2 neglected and not yet well-defined celiac phenotypes, that is, seronegative and ultrashort CeD. Seronegative CeD can be suspected in the presence of flat villi, positive HLA-DQ2 and/or HLA-DQ8, and the absence of CeD antibodies. After ruling out other seronegative enteropathies, the diagnosis can be confirmed by both clinical and histologic improvements after 1 year of a gluten-free diet. Ultrashort CeD is characterized by the finding of flat villi in the duodenal bulb in the absence of mucosal damage in the distal duodenum and with serologic positivity. Data on the prevalence, clinical manifestations, histologic lesions, genetic features, and outcome of seronegative and ultrashort CeD are inconclusive due to the few studies available and the small number of patients diagnosed. Some additional diagnostic tools have been developed recently, such as assessing intestinal transglutaminase 2 deposits, flow cytometry technique, microRNA detection, or proteomic analysis, and they seem to be useful in the identification of complex cases. Further cooperative studies are highly desirable to improve the knowledge of these 2 still-obscure variants of CeD.

Serum anti-tissue transglutaminase IgA and prediction of duodenal villous atrophy in adults with suspected coeliac disease without IgA deficiency (Bi.A.CeD): a multicentre, prospective cohort study.

BACKGROUND: Whether coeliac disease in adults can be diagnosed with serology alone remains controversial. We aimed to evaluate the accuracy of serum anti-tissue transglutaminase IgA (tTG-IgA) in the diagnosis of coeliac disease. METHODS: In this multicentre, prospective cohort study, adult participants (aged ≥18 years) with suspected coeliac disease without IgA deficiency who were not on a gluten-free diet and who had a local serum tTG-IgA measurement, were enrolled from Feb 27, 2018, to Dec 24, 2020, by 14 tertiary referral centres (ten from Europe, two from Asia, one from Oceania, and one from South America) to undergo local endoscopic duodenal biopsy. Local serum tTG-IgA was measured with 14 different test brands and concentration expressed as a multiple of each test's upper limit of normal (ULN), and defined as positive when greater than 1 times the ULN. The main study outcome was the reliability of serum tests for the diagnosis of coeliac disease, as defined by duodenal villous atrophy (Marsh type 3 or Corazza-Villanacci grade B). Histology was evaluated by the local pathologist, with discordant cases (positive tTG-IgA without duodenal villous atrophy or negative tTG-IgA with duodenal villous atrophy) re-evaluated by a central pathologist. The reliability of serum tests for the prediction of duodenal villous atrophy was evaluated according to sensitivity, specificity, positive predictive value, negative predictive value, and the area under the receiver operating characteristic curve (AUC) for categorical and continuous data. FINDINGS: We enrolled 436 participants with complete local data on serum tTG-IgA and duodenal histology (296 [68%] women and 140 [32%] men; mean age 40 years [SD 15]). Positive serum tTG-IgA was detected in 363 (83%) participants and negative serum tTG-IgA in 73 (17%). Of the 363 participants with positive serum tTG-IgA, 341 had positive histology (true positives) and 22 had negative histology (false positives) after local review. Of the 73 participants with negative serum tTG-IgA, seven had positive histology (false negatives) and 66 had negative histology (true negatives) after local review. The positive predictive value was 93·9% (95% CI 89·2-98·6), the negative predictive value was 90·4% (85·5-95·3), sensitivity was 98·0% (95·3-100·0), and specificity was 75·0% (66·6-83·4). After central re-evaluation of duodenal histology in 29 discordant cases, there were 348 true positive cases, 15 false positive cases, 66 true negative cases, and seven false negative cases, resulting in a positive predictive value of 95·9% (92·0-99·8), a negative predictive value of 90·4% (85·5-95·3), a sensitivity of 98·0% (95·3-100·0), and a specificity of 81·5% (73·9-89·1). Either using the local or central definition of duodenal histology, the positive predictive value of local serum tTG-IgA increased when the serological threshold was defined at increasing multiples of the ULN (p<0·0001). The AUC for serum tTG-IgA for the prediction of duodenal villous atrophy was 0·87 (95% CI 0·81-0·92) when applying the categorical definition of serum tTG-IgA (positive [>1 × ULN] vs negative [≤1 × ULN]), and 0·93 (0·89-0·96) when applying the numerical definition of serum tTG-IgA (multiples of the ULN). Additional endoscopic findings included peptic gastritis (nine patients), autoimmune atrophic gastritis (three), reflux oesophagitis (31), gastric or duodenal ulcer (three), and Barrett's oesophagus (one). In the 1-year follow-up, a midgut ileum lymphoma was diagnosed in a woman on a gluten-free diet. INTERPRETATION: Our data showed that biopsy could be reasonably avoided in the diagnosis of coeliac disease in adults with reliable suspicion of coeliac disease and high serum tTG-IgA. FUNDING: None.

The differential diagnoses for severe enteropathy or severely damaged small intestinal mucosa.

Aim: The aim of this study was to explore the aetiology of severe duodenal mucosal abnormality in consecutive patients who underwent gastroscopy and duodenal biopsy over the past 10 years. Background: A range of differential diagnoses have been reported for severe duodenal architectural distortion. Methods: Clinical and laboratory data of all the patients with severe duodenal architectural distortion diagnosed at MidCentral District Health Board (DHB), New Zealand were collected and statistically analysed. Ninety-five percent confidence intervals (CI) are shown. Results: Between September 2009 and April 2019, 229 patients were diagnosed with severe enteropathy. The median patient age was 41 years (range 6-83 years). Two hundred and twenty-four of these patients (97.8%, 95.0-99.3%) were diagnosed with coeliac disease (CeD), with one of these patients having gluten induced T-cell lymphoma. From the remaining five patients, one had a diagnosis of tropical sprue and four did not have a clear aetiology. There were 180 patients from 191 (94.2%, 89.9-97.1%) with at least one positive coeliac marker, all with a diagnosis of CeD. Eleven patients (5.8% of 191, 2.9-10.1%) had negative markers for both tissue transglutaminase IgA (tTG-IgA) and IgA-endomysial antibodies (EMA-IgA) with six having a diagnosis of seronegative CeD. Conclusion: Although the spectrum of histological changes in CeD may range from normal to a flat mucosa, severe duodenal architectural distortion seems to occur mainly in CeD. Idiopathic enteropathy was recorded as the second but by far less frequent presentation of severe enteropathy. This study highlights that infection and other aetiologies are rarely implicated in severe enteropathy, with one case (0.4%) of refractory CeD/T-cell lymphoma.

Nomenclature and diagnosis of seronegative coeliac disease and chronic non-coeliac enteropathies in adults: the Paris consensus.

OBJECTIVE: Differential diagnosis of villous atrophy (VA) without coeliac antibodies in adults includes seronegative coeliac disease (CD) and chronic enteropathies unrelated to gluten, ie. non-coeliac enteropathies (NCEs). There is currently no international consensus on the nomenclature and diagnostic criteria for these enteropathies. In this work, a Delphi process was conducted to address this diagnostic and clinical uncertainty. DESIGN: An international task force of 13 gastroenterologists from six countries was recruited at the 16th International Coeliac Disease Symposium, Paris, 2019. Between September 2019 and July 2021, a Delphi process was conducted through mail surveys to reach a consensus on which conditions to consider in the differential diagnosis of VA with negative coeliac serology and the clinical diagnostic approaches required for these conditions. A 70% agreement threshold was adopted. RESULTS: Chronic enteropathies characterised by VA and negative coeliac serology can be attributed to two main clinical scenarios: forms of CD presenting with negative serology, which also include seronegative CD and CD associated with IgA deficiency, and NCEs, with the latter recognising different underlying aetiologies. A consensus was reached on the diagnostic criteria for NCEs assisting clinicians in differentiating NCEs from seronegative CD. Although in adults seronegative CD is the most common aetiology in patients with VA and negative serology, discriminating between seronegative CD and NCEs is key to avoid unnecessary lifelong gluten-free diet, treat disease-specific morbidity and contrast poor long-term outcomes. CONCLUSION: This paper describes the Paris consensus on the definitions and diagnostic criteria for seronegative CD and chronic NCEs in adults.

Gluten Induces Subtle Histological Changes in Duodenal Mucosa of Patients with Non-Coeliac Gluten Sensitivity: A Multicentre Study.

Background: Histological changes induced by gluten in the duodenal mucosa of patients with non-coeliac gluten sensitivity (NCGS) are poorly defined. Objectives: To evaluate the structural and inflammatory features of NCGS compared to controls and coeliac disease (CeD) with milder enteropathy (Marsh I-II). Methods: Well-oriented biopsies of 262 control cases with normal gastroscopy and histologic findings, 261 CeD, and 175 NCGS biopsies from 9 contributing countries were examined. Villus height (VH, in µm), crypt depth (CrD, in µm), villus-to-crypt ratios (VCR), IELs (intraepithelial lymphocytes/100 enterocytes), and other relevant histological, serologic, and demographic parameters were quantified. Results: The median VH in NCGS was significantly shorter (600, IQR: 400−705) than controls (900, IQR: 667−1112) (p < 0.001). NCGS patients with Marsh I-II had similar VH and VCR to CeD [465 µm (IQR: 390−620) vs. 427 µm (IQR: 348−569, p = 0·176)]. The VCR in NCGS with Marsh 0 was lower than controls (p < 0.001). The median IEL in NCGS with Marsh 0 was higher than controls (23.0 vs. 13.7, p < 0.001). To distinguish Marsh 0 NCGS from controls, an IEL cut-off of 14 showed 79% sensitivity and 55% specificity. IEL densities in Marsh I-II NCGS and CeD groups were similar. Conclusion: NCGS duodenal mucosa exhibits distinctive changes consistent with an intestinal response to luminal antigens, even at the Marsh 0 stage of villus architecture.

Is duodenal biopsy always necessary for the diagnosis of coeliac disease in adult patients with high anti-tissue transglutaminase (TTG) antibody titres?

Objective: Avoiding duodenal biopsy in adults for coeliac disease (CD) diagnosis is controversial. Some retrospective and prospective studies have shown that CD can be reliably diagnosed in adults with serology rather than duodenal biopsies. This study aimed to check the accuracy of a cut-off value of ≥10 upper limit of normal of anti-tissue transglutaminase antibody (anti-TTG IgA) titres for CD diagnosis in adult patients. Method: We retrospectively analysed adult patients (≥16 years) who underwent gastroscopy from 2013 to 2018 for positive coeliac serology. The relationship between titres and disease was determined by using linear models, whereas sensitivity and specificity were assessed by receiver operator curve. Results: We analysed 144 newly anti-TTG antibody-positive adult patients with a median age of 48.5 years (IQR 32-62); among them, 86 (60%) patients had CD (Marsh III: n=68 and Marsh II and I: n=18) with a higher prevalence in females (n=59 (69%)) and Europeans (n=60 (70%)). Fifty (58%) patients with CD had colonoscopy and five (6%) had imaging; only six patients were diagnosed with additional conditions. An anti-TTG IgA titre cut-off value of 150 U/L was 100% specific for CD in our dataset, with 70% (95% CI: 60% to 88%) sensitivity for this patient group. Conclusion: Coeliac serology using anti-TTG IgA with titres ≥10× normal value is an excellent predictor of CD, irrespective of age, gender and ethnicity. Duodenal biopsy may not be necessary in selected adult patients with CD, especially younger than 50 years of age without additional gastrointestinal red-flag signs and symptoms.

Toward finding the difference between untreated celiac disease and COVID-19 infected patients in terms of CD4, CD25 (IL-2 Rα), FOXP3 and IL-6 expressions as genes affecting immune homeostasis.

BACKGROUND: Coronavirus disease 2019 (COVID-19) is defined as an emerging infectious disease caused by severe acute respiratory syndrome coronavirus 2 and celiac disease (CD) is one of the autoimmune multiorgan diseases, which can be accompanied by an increased risk of viral infections. CD patients, especially untreated subjects, may be at greater risk of infections such as viral illnesses. Interleukin (IL)-6, CD4, CD25, and FOXP3 are known as genes affecting immune homeostasis and relate to the inflammation state. This study aimed to compare the expression levels of aforementioned genes in peripheral blood samples of CD and severe COVID-19 patients. METHODS: Sixty newly diagnosed CD patients with median age (mean ± SD) of 35.40 ± 24.12 years; thirty confirmed severe COVID-19 patients with median age (mean ± SD) of 59.67 ± 17.22, and 60 healthy subjects with median age (mean ± SD) of 35.6 ± 13.02 years; were recruited from March to September 2020. Fresh whole blood samples were collected, total RNA was obtained and cDNA synthesis was carried out. RNA expression levels of IL-6, CD4, CD25, and FOXP3 genes were assessed using real-time quantitative RT-PCR according to the 2-∆∆Ct formula. Statistical analysis was performed using SPSS (V.21) and GraphPad, Prism (V.6). RESULTS: While increased expression of CD4, CD25, and FOXP3 was observed in CD patients compared to the control group (p = 0.02, p = 0.03, and p < 0.0001 respectively) and COVID-19 patients group (p < 0.0001 for all of them), their expression levels in COVID-19 patients decreased compared to controls (p < 0.0001, p = 0.01, p = 0.007, respectively). Increased IL-6 expression was observed in both groups of patients compared to controls (p < 0.0001 for both of them). CONCLUSIONS: Although untreated CD patients may be at greater risk of developing into severe COVID-19 if they are infected by SARS-CoV-2 virus (due to their high expression of IL-6), increased expression of anti-inflammatory markers in these patients may be beneficial for them with the ability of reducing the severity of COVID-19 disease, which needs to be proven in future studies involving celiac patients infected with COVID-19.

Symptomatic giant gastric hyperplastic polyp: a case report.

Herein we describe a rare case of a 59-year-old male who was diagnosed with giant hyperplastic polyps after referring with symptoms of abdominal pain and vomiting, and associated red-flag symptoms of unintentional weight loss and early satiety.

Prevalence of celiac disease in low and high risk population in Asia-Pacific region: a systematic review and meta-analysis.

This systematic review and meta-analysis study was conducted to estimate the pooled prevalence of CD in low and high risk groups in this region. Following keywords were searched in the Medline, PubMed, Scopus, Web of Science and Cochrane database according to the MeSH terms; celiac disease, prevalence, high risk population and Asian-Pacific region. Prevalence studies published from January 1991 to March 2018 were selected. Prevalence of CD with 95% confidence interval (CI) was calculated using STATA software, version 14. The pooled sero-prevalence of CD among low risk group in Asia-Pacific region was 1.2% (95% CI 0.8-1.7%) in 96,099 individuals based on positive anti-tissue transglutaminase (anti-t-TG Ab) and/or anti-endomysial antibodies (EMA). The pooled prevalence of biopsy proven CD in Asia-Pacific among high and low risk groups was 4.3% (95% CI 3.3-5.5%) and 0.61% (95% CI 0.4-0.8%) in 10,719 and 70,344 subjects, respectively. In addition, the pooled sero-prevalence and prevalence of CD in general population was significantly higher in children compared with adults and it was significantly greater in female vs. male (P < 0.05). Our results suggest high risk individuals of CD are key group that should be specifically targeted for prevention and control measures, and screening may prove to have an optimal cost-benefit ratio.

Accuracy of a no-biopsy approach for the diagnosis of coeliac disease across different adult cohorts.

OBJECTIVE: We aimed to determine the predictive capacity and diagnostic yield of a 10-fold increase in serum IgA antitissue transglutaminase (tTG) antibody levels for detecting small intestinal injury diagnostic of coeliac disease (CD) in adult patients. DESIGN: The study comprised three adult cohorts. Cohort 1: 740 patients assessed in the specialist CD clinic at a UK centre; cohort 2: 532 patients with low suspicion for CD referred for upper GI endoscopy at a UK centre; cohort 3: 145 patients with raised tTG titres from multiple international sites. Marsh 3 histology was used as a reference standard against which we determined the performance characteristics of an IgA tTG titre of ≥10×ULN for a diagnosis of CD. RESULTS: Cohort 1: the sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) for IgA tTG levels of ≥10×ULN at identifying individuals with Marsh 3 lesions were 54.0%, 90.0%, 98.7% and 12.5%, respectively. Cohort 2: the sensitivity, specificity, PPV and NPV for IgA tTG levels of ≥10×ULN at identifying individuals with Marsh 3 lesions were 50.0%, 100.0%, 100.0% and 98.3%, respectively. Cohort 3: the sensitivity, specificity, PPV and NPV for IgA tTG levels of ≥10×ULN at identifying individuals with Marsh 3 lesions were 30.0%, 83.0%, 95.2% and 9.5%, respectively. CONCLUSION: Our results show that IgA tTG titres of ≥10×ULN have a strong predictive value at identifying adults with intestinal changes diagnostic of CD. This study supports the use of a no-biopsy approach for the diagnosis of adult CD.

Serum Level and Gene Expression of Interleukin-15 Do Not Correlate with Villous Atrophy in Celiac Disease Patients.

Background and Aims: Interleukin-15 (IL-15) is a key player in the pathogenesis of celiac disease (CD). We investigated the functional role of IL-15 in the process of epithelial cell phenotypic modification at different stages of CD. Materials and Methods: In this study, we looked for correlations between the IL-15 mRNA levels in duodenal tissue and serum protein levels in a cohort of Iranian patients affected by CD based on the degree of histopathology. Ninety-five formalin-fixed, paraffin-embedded duodenal tissue specimens were collected: 23 with a Marsh I value; 30 with a Marsh II value; 32 with a Marsh III value; and 10 normal controls. The expression levels of the IL-15 gene in these biopsy specimens were determined by real-time quantitative polymerase chain reaction (qPCR), and IL-15 serum protein concentrations were determined by enzyme-linked immunosorbent assay and compared to tissue expression. Results: The IL-15 mRNA levels were higher in patients with Marsh II compared with the control group, and the Marsh I, and Marsh III groups. The differences between the Marsh II and Marsh I patients were statistically significant (p = 0.03). Similarly, the serum concentration of IL-15 was higher in Marsh II patients compared to those with Marsh I and Marsh III lesions, although the differences were not statistically significant (p = 0.221). Conclusions: Our results demonstrate that IL-15 gene expression might be elevated only in the early stages of CD onset (and histological damage) and that IL-15 serum levels do not significantly correlate with its tissue expression whatever the degree of histopathology.

The value of a biopsy in celiac disease follow up: assessment of the small bowel after 6 and 24 months treatment with a gluten free diet.

INTRODUCTION: a routine small bowel biopsy (SBB) during the follow up of celiac disease (CD) is controversial. Little information is available regarding the histological changes during (gluten free diet (GFD) in the long term. OBJECTIVES: the aim of the study was to evaluate a novel criterion to compare duodenal histology in CD patients after six months and two years of gluten withdrawal. METHODS: this was a cross-sectional study of 200 patients with confirmed Marsh I-III who were under the six months (group A, n = 100) and 24 months (group B, n = 100) of a GFD. Nineteen patients were excluded due to an inadequate adherence to the GFD and another 23 patients were excluded as they were unwilling to undergo a re-endoscopy and did not comply with the necessary criteria. Endoscopy with a duodenal biopsy, serological assays and clinical evaluation were performed and compared with baseline data in the remaining 58 patients (20 patients in group A and 38 patients in group B). RESULTS: a significant complete histological recovery was found in 47.4% of patients in group B compared to 30% in group A (p = 0.026). A partial histological recovery was reported in seven (35%) and eleven (28.9%) patients in groups A and B, respectively. Any changes in mucosal histology after GFD was observed in 35% of patients in group A and 23.7% in group B. Serological assessment and endoscopic appearance normalized in 78.9% vs 75.0% in group B and 68.4% vs 65.0% in group A, respectively. However, this improvement did not reach statistical significance (p > 0.05). CONCLUSIONS: the results of this study show that histological recovery in patients with Marsh ≥ III is slow and does not correlate with symptomatic improvement. We suggest that the long-term effects of a GFD can play an important role in achieving histological improvement, especially in older patients.

The role of CXCR3 and its ligands CXCL10 and CXCL11 in the pathogenesis of celiac disease.

The chemokine receptor CXCR3 and its ligands CXCL10 and CXCL11 have been suggested to give rise to the most relevant chemokine axis able to facilitate the entrance of immune cells into inflamed tissues and be activated in different inflammatory disorders, such as celiac disease (CD).The aim of this study was to investigate the expression level of CXCR3, CXCL10, and CXCL11 genes in celiac patients compared to healthy controls. Both cohorts have been recruited from the Iranian population.In this case-control study, biopsy specimens were collected from 71 celiac patients (60.5% female) and 90 control subjects (57% female) during 2016. Total RNA was extracted and mRNA expression levels of CXCR3, CXCL10, and CXCL11 genes were investigated by SYBR green qPCR.Based on qPCR and relative quantification method, the mRNA expression levels of CXCR3, CXCL10, and CXCL11 were significantly higher in duodenal biopsies of celiac patients compared to healthy controls in the study population (P = .038, P = .021, and P = .012 respectively).The result of this study showed that CXCR3/CXCL10/CXCL11 signaling axis is overexpressed in the small intestinal mucosa of CD patients compared to controls. This finding might explain the specific enrollment of the main cell populations that infiltrate the epithelium.

Contribution of HLA-DQ2/DQ8 haplotypes in type one diabetes patients with/without celiac disease.

BACKGROUND: Based on lack of data on the distribution of the related alleles in the T1D population in Iranian population, we assessed the frequency of HLA DQ2 and DQ8 haplotypes in patients with T1D with/without CD compared to healthy population. MATERIALS AND METHODS: 70 patients with T1D without celiac disease, 60 T1D cases with CD were compared to 150 healthy individuals during 2016. Ten mililiter Gheparinized blood samples were collected, genomic DNA was extracted and alleles were genotyped by Real-time PCR using SYBR Green as a low-resolution method. RESULTS: HLA-DQ2 and/or HLA-DQ8 genotypes was presented in 51% and 23% of T1D patients without CD respectively. Twenty one percent of those patients carried both alleles and 5% were negative for both alleles. T1D patients with CD had much higher DQ2 frequency (72%) and lower DQ8 (11.6%), than T1D patients without CD and controls, 14% carried both alleles and 3% were negative for both. The frequencies of DQ2 and DQ8 alleles in Iranian healthy population were 19 and 5% respectively. CONCLUSION: According to the same genetic background for CD and T1D we suggest that HLA-typing can be a very useful screening tool for CD in patients with type one diabetes.

Diverse Profiles of Toll-Like Receptors 2, 4, 7, and 9 mRNA in Peripheral Blood and Biopsy Specimens of Patients with Celiac Disease.

BACKGROUND AND AIMS: Both adaptive and innate immunity are involved in the development of celiac disease (CD). Altered Toll-like receptors (TLR) expression and activation may be partially responsible for the inflammation and subsequently crypt hyperplasia, but the main driver for inflammation is gliadin-reactive T-cells. Therefore, the aim of this study was to investigate the TLRs 2, 4, 7, and 9 gene expressions in both peripheral blood and intestinal mucosa of patients with celiac disease compared to healthy control (HC). MATERIAL AND METHODS: Blood samples from 120 confirmed active CD patients and 120 age- and sex-matched healthy volunteers served as control group were collected during 2015-2016. Also, 20 biopsy specimens from the study group were randomly collected. Total RNA was isolated using a standard commercial kit. The mRNA expression of TLRs was quantified by relative qPCR with ß2 microglobulin (ß2m) as a reference gene. RESULTS: TLR4 (P = 0.01) and TLR9 (P = 0.02) mRNA were significantly elevated in blood samples from CD patients compared to the healthy controls. Moreover, TLR2 (P = 0.03) and TLR4 (P = 0.0003) expression level was increased in CD biopsy specimens compared to controls, whereas expression of TLR9 mRNA was significantly decreased in CD patients. There was no significant difference in the expression of TLR7 in biopsy and blood specimens. CONCLUSIONS: The alteration of TLR4 and TLR9 expression in the blood and biopsy samples of patients with CD supports the critical role of the innate immune system in the pathogenesis of this disease. Upregulation of TLR4 and TLR9 suggests the contribution of gut microbiota or dysregulation of the immune response to commensal flora in small bowel mucosa in celiac patients.