Marsh Grade Research Articles

Serum anti-mullerian hormone, sex hormone, and nutrient levels in reproductive age women with celiac disease.

This study aimed to investigate the changes in serum Anti-Müllerian Hormone (AMH) levels, sex hormone levels, follicle-stimulating hormone (FSH)/luteinizing hormone (LH) ratio in patients with celiac disease (CeD), and their correlation with clinical characteristics and nutrient levels. This cross-sectional study collected clinical and biochemical data from a total of 67 females diagnosed with CeD and 67 healthy females within the reproductive age range of 18-44 years. The study was conducted at a tertiary hospital between September 2016 and January 2024. Both groups underwent comprehensive clinical and laboratory assessments. Serum levels of AMH and sex hormones were quantified using chemiluminescence immunoassay, and their associations with CeD clinical features and nutrient levels were thoroughly analyzed. The study included 67 patients and 67 controls with a mean age of 36.7±7.6 years. No statistically significant differences were found between the two groups in mean age, BMI, FSH, LH, E2, P levels, FSH/LH, menstrual irregularities, abortions history, parity, and gravidity (all P>0.05). However, AMH, T, FER, FA, Zn, and Se levels were significantly lower, and PRL levels were higher in the CeD group (all P<0.05). Spearman's correlation analysis showed that AMH levels were negatively correlated with age, tTG level, disease duration, and Marsh grading (P<0.05). This study highlights the association between impaired ovarian function in CeD patients and disease severity and nutrient levels. Early detection and intervention for ovarian function abnormalities are imperative to enhance fertility potential in CeD patients.

Positive association of serum IgG4 levels with modified marsh classification system in children with gluten enteropathy: a single centre experience

Background: Celiac disease or gluten enteropathy is an immune-mediated systemic disorder elicited by gluten and related prolamines in genetically susceptible individuals and is characterized by the presence of gluten enteropathy, celiac disease-specific antibodies, HLA-DQ2/DQ8 haplotypes. IgG4-related diseases is an increasingly recognized immune-mediated condition in autoimmune disorders such as primary sclerosing cholangitis, autoimmune hepatitis, and autoimmune thyroiditis, characterized by tissue fibrosclerosis and infiltration by IgG4-positive plasma cells and increased serum IgG4 concentrations. Methods: A total of 33 children with newly diagnosed celiac disease and 31 control subjects were included in this study. All suspected celiac disease children underwent duodenal biopsy and were diagnosed based on Marsh grading. Serum IgG4 level estimations were performed using an enzyme-linked immune sorbet assay method with a cut-off of 135 mg/dl for diagnosis. Results: A significant positive association between serum IgG4 levels and Marsh classification was found, the higher the levels of IgG4 in serum, the higher the grade on Marsh staging. Mean serum IgG4 levels in Marsh 3a was 126.32 mg/dl, in 3b was 171.35 mg/dl and in 3c was 209.24 mg/dl (p value=0.004) Conclusions: With increasing serum IgG4 levels, increased severity of damage was seen on biopsy specimens based on higher Marsh grade. To the best of found knowledge, this is the first study to establish the relation between IgG4 and mucosal damage in children with celiac disease.

Feasibility of a "No-Biopsy" Approach for the Diagnosis of Celiac Disease in Symptomatic Adults.

It was a retrospective analysis of medical records of all biopsy-diagnosed CD patients with available anti-tTGA antibodies reports from 2019 to 2023. The patients were divided into three groups based on Marsh grading and anti-tTGA antibody levels were compared using various statistical tests. A total of 94 biopsy-diagnosed symptomatic CD patients with anti-tTGA antibody reports available formed the study group. Of these, 54 had biopsy findings consistent with Marsh 3 lesion, three had Marsh 2 lesion, and 37 had Marsh 1 lesion. A significant correlation existed between Marsh grading 3 lesion and anti-tTGA antibody levels above the upper limit of normal (ULN) x 10. Serum levels of anti-tTGA antibodies greater than 10 x ULN can be used to identify symptomatic patients with Marsh grade 3 CD lesions.

Correlation between intestinal stem cell niche changes and small bowel crypt failure in patients with treatment-naïve celiac disease.

We hypothesized that crypt failure in the small bowel results in villous flattening in patients with celiac disease (CeD). We investigated whether alterations in the stem cell niche (ISC) are responsible for this phenomenon. We included 92 duodenal (D2/3) biopsies from treatment-naive patients of CeD and 37 controls. All underwent screening for serum anti-tissue transglutaminase and endoscopic upper small bowel biopsy. Immunohistochemical markers were used to investigate ISC niche alterations, including LGR5 for crypt basal cells (CBC), Bmi1 for position 4+ cells, β-Defensin for Paneth cells, R-spondin1 as WNT activator, transcription factor-4 as WNT transcription factor, BMP receptor1A as WNT inhibitor, fibronectin-1 as periepithelial stromal cell marker, H2AX as apoptosis marker, and Ki67 as proliferation marker. We also analyzed IgA anti-tTG2 antibody deposits by using dual-color immunofluorescence staining. We found that in biopsies from patients with treatment-naive CeD with modified Marsh grade 3a-3c changes, the epithelial H2AX apoptotic index was upregulated than in controls. LGR5+ crypt basal cells were upregulated in all modified Marsh grades compared to controls. However, the Ki67 proliferation index, expressions of WNT-activator RSPO1, and position-4 cell marker Bmi1 did not significantly alter in patients' biopsies as compared to controls ( P = 0.001). We also observed depletion of pericrypt stromal fibronectin-1 in patients with CeD compared to controls. In addition, we identified IgA anti-TG2 antibody deposits in pericrypt stroma. Our data suggests that ISC niche failure is a plausible hypothesis for villous flattening in patients with CeD, resulting from pericrypt IgA anti-TG2 antibody complex-mediated stromal depletion.

Accuracy of the No-Biopsy Approach for the Diagnosis of Celiac Disease in Adults: A Systematic Review and Meta-Analysis

Background & AimsCurrent international guidelines recommend duodenal biopsies to confirm the diagnosis of coeliac disease in adult patients. However, growing evidence suggests that IgA anti-tissue transglutaminase (tTg) antibody levels ≥10 times the upper limit of normal (ULN) can accurately predict coeliac disease, eliminating the need for biopsy. We performed a systematic review and meta-analysis to evaluate the accuracy of the no-biopsy approach to confirm the diagnosis of coeliac disease in adults. MethodsWe systematically searched MEDLINE, EMBASE, Cochrane Library and Web of Science from January 1998 to October 2023 for studies reporting the sensitivity and specificity of IgA-tTG ≥10×ULN against duodenal biopsies (Marsh grade ≥2) in adults with suspected coeliac disease. We used a bivariate random-effects model to calculate the summary estimates of sensitivity, specificity, positive and negative likelihood ratios. The positive and negative likelihood ratios were used to calculate the positive predictive value (PPV) of the no-biopsy approach across different pre-test probabilities of coeliac disease. The methodological quality of the included studies was evaluated using the QUADAS-2 tool. This study was registered with PROSPERO, number CRD42023398812. ResultsA total of 18 studies comprising 12,103 participants from 15 countries were included. The pooled prevalence of biopsy-proven coeliac disease in the included studies was 62% (95% CI, 40% - 83%). The proportion of patients with IgA-tTG ≥10×ULN was 32% (95% CI, 24% - 40%). The summary sensitivity of IgA-tTG ≥10×ULN was 51% (95% CI, 42% - 60%), and the summary specificity was 100% (95% CI, 98% - 100%). The area under the summary receiver operating characteristic curve was 0.83 (95% CI, 0.77 – 0.89). The PPV of the no-biopsy approach to identify patients with coeliac disease was 65%, 88%, 95%, and 99% if coeliac disease prevalence was 1%, 4%, 10% and 40%, respectively. Between-study heterogeneity was moderate (I2 =30.3%), and additional sensitivity analyses did not significantly alter our findings. Only one study had a low risk of bias across all domains. ConclusionThe results of this meta-analysis suggest that selected adult patients with IgA-tTG ≥10×ULN and a moderate to high pre-test probability of coeliac disease could be diagnosed without undergoing invasive endoscopy and duodenal biopsy.

Gluten Enteropathy in Adult Iraqi Patients: Immunological and Histopathological Assessment (A Cross-Sectional Study)

Background: Gluten-enteropathy or Celiac disease (CD) is a well-known autoimmune gastroenteropathy. The disease incidence is globally like an iceberg with many cases are believed to be undiscovered in the community. Many researches are continuously done to detect the pathogenesis of the disease. Soluble Interleukin-2 receptor (sIL-2R) is well a mediator involved in the inflammatory process including celiac disease. ELISA technique was used to evaluate the serum level of sIL-2R, anti- tissue tTG IgA and anti-deamidated gliadin peptide (DGP) IgG. The duodenal histological changes were evaluated dependent on the MARSH grading system. Forty five patients were included in this cross-sectional study with other 45 healthy persons as control group. Statistical analysis using the SPSS system revealed the followings facts. Aim: This study aimed to assess the level of sIL-2R in association with duodenal histopathological changes in CD together with other serological and clinical parameters in comparison with healthy individuals (control group). Materials and Methods: A forty five patients were included in this cross-sectional study with other forty five healthy persons as control group. Statistical analysis using the SPSS system to reveal the followings facts. Results: Anemia was present in most of patients. The patients with celiac disease had high levels of serum anti-tTG, DGP &amp; s.IL-2 receptors with significant difference in comparison with the control group (P&lt; 0.05). MARSH grades were highly significant with the immunological markers. Conclusion: CD can be a hidden disease with variable severity modes that can be monitored by immunological and pathological methods. Soluble IL-2R antibody is a good tool to assess CD activity and patient compliance.

Celiac Disease in Uzbek Children: Insights into Disease Prevalence and Clinical Characteristics in Symptomatic Pediatric Patients.

A few studies on pediatric Celiac Disease (CD) are available from Central Asia. Recent immunogenetic research has highlighted that the HLA-DQ2/8 genetic predisposition to CD as well as the dietary intake of gluten in this geographical area, are comparable to other regions of the world where CD prevalence is known to be 1% or higher. This is a prospective and cross-sectional study investigating the prevalence and clinical characteristics of CD in symptomatic children referred to the pediatric gastroenterology department of a tertiary hospital in Uzbekistan from 1 September 2021, until 31 July 2022. In addition to collecting the relevant information related to clinical manifestations and laboratory analyses from the clinical files, a specific survey was also administered to patients' guardians. Serological, histopathological, and immunogenetic parameters specific to CD, fecal zonulin, and pancreatic elastases were assessed in CD patients. The study population consisted of 206 children. Overall, almost all of them (n = 192; 93.2%) were referred because of gastrointestinal manifestations, which were associated with extra-gastrointestinal manifestations in most cases (n = 153; 74.3%); a minority (n = 14; 6.8%) was mainly referred due short stature and/or growth failure only. Among all of these study participants, CD was diagnosed in 11 children (5.3%). Notably, although diarrhea was similarly reported in CD and non-CD patients, watery diarrhea (type 7 according to the Bristol stool scale) was much more frequently and significantly observed in the former group. All of these CD patients showed anti-tTG IgA 10 times higher than the upper normal limit, except one child with lower serum levels of total IgA; however, all of them received a diagnostic confirmation by histopathological analysis due to the lack of EMA testing in the country. Notably, most CD children (82%) showed a Marsh III histological grading. Around half patients (54.5%) showed zonulin values above the reference range, whereas none showed insufficient levels of pancreatic elastase. However, no correlation or association between zonulin and clinical, laboratory, histopathological, and immunogenetic parameters was found. This study may further suggest a relevant prevalence of CD in Uzbek children, based on this partial picture emerging from symptomatic patients only. Additionally, we highlighted the prevalence of typical CD forms with watery diarrhea, which should strongly support a full diagnostic work-up for CD in the local clinical setting. The high levels of anti-tTG IgA and high Marsh grade might also lead us to speculate a significant diagnostic delay despite the classical clinical expression of CD.

The strategic use of biopsy in the diagnosis of coeliac disease in adults

BackgroundThe paediatric guidelines support the use of the ‘No Biopsy Approach’ in the diagnosis of coeliac disease (CD). We aimed to determine the correlation between anti tissue transglutaminase (anti-TTG serology) ≥10 times the upper limit of normal (ULN), using the Celikey ® ELiA assay and histological findings. Our secondary aim was to determine the safety of this approach in our centre. MethodsA retrospective analysis of adult patients referred to a tertiary referral centre with raised anti-TTG titres and/or histological changes of coeliac on D2 biopsies between 2014 – 2019. Excluded patients were those who did not have a biopsy performed, or whose biopsy was unavailable for review, selective IgA deficiency, and gluten elimination prior to biopsy. Biopsies were classified according to Marsh, by two independent pathologists, blinded to the anti-TTG titre. Results164 patients had positive anti-TTG serology and duodenal biopsy in our centre prior to starting a gluten free diet (GFD) in the period 2014 - 2019. Of these 164 patients (median age 40yrs, 62% female), 68 (33%) had an anti-TTG titre ≥10 x ULN, 99% of which had a Marsh grading ≥ 3 and 1% had a Marsh of 2 on biopsy. 91% had either a normal index gastroscopy or findings of mild gastritis/oesophagitis. ConclusionsWe found a 98.5% positive predictive value (PPV) of determining CD (i.e., Marsh ≥ 3) in those with an anti-TTG ≥10 x ULN. In those with moderate to high-risk clinical suspicion of CD we propose that duodenal biopsy is unnecessary for diagnosis.

Celiac Disease Screening in the Siblings of Pediatric Patients with a Confirmed Diagnosis: A Cross-sectional Study

Background: The close relatives of patients with celiac disease (CD), particularly their siblings, are known to be at a higher risk for CD development. Objectives: Our aim was to determine the prevalence of CD in siblings of confirmed CD patients in Lorestan province, Iran, in 2020. Methods: In this cross-sectional study, anti-tissue transglutaminase (tTG) antibody levels were measured in 140 siblings of children with CD. Duodenal biopsies were taken to confirm the diagnosis in those with positive serological tests. The subjects’ demographic and clinical data were recorded into a pre-designed questionnaire, and the collected data were analyzed by SPSS software version 22 at a significance level of 0.05. Results: Twelve out of 140 subjects (8.6%) tested positive for tTG IgA, eight of them (66.7%) were girls, and most of them (75%) were ≤ 15 years old. Half of the newly diagnosed patients were in the Marsh IIIc category. The Marsh grading had no significant relationship with the serum levels of tTG IgA antibodies (P = 0.319). The most common gastrointestinal symptom was bloating (66.7%), and the most common extraintestinal symptoms were anemia (58.3%) and dental and oral diseases (58.3%). Conclusions: We found a high prevalence (8.6%) of CD among the siblings of children with confirmed CD. Since the early diagnosis of CD can lead to better management, particularly in pediatrics, it is recommended screen patients’ family members as soon as the diagnosis of CD is confirmed.

Utility of human leukocyte antigen DQ2 and DQ8 genotypes in Celiac disease: Two sides of the coin

Human Leukocyte Antigen (HLA) DQ2 and DQ8 are the known risk genotypes for Celiac Disease. Diagnosis of celiac disease requires serology testing and intestinal biopsy however, genetic testing could also be implemented because of its high negative predictive value. Our study, initiated prior to the publication of 2020 guidelines, evaluated the utility of HLA DQ2 and DQ8 genotyping in the cohort of 537 children with celiac disease and their 1420 first-degree relatives. We attempted to evaluate its applicability in low-middle-income countries like India. Prevalence of celiac disease was observed at 18.52% and 15.68% based on serological and histopathological diagnosis in first-degree relatives. HLA DQA1*0501 and DQB1*0201 alleles were the most frequently observed alleles in index cases (84.4% versus 86.4%), biopsy proven first-degree relatives (77.9% vs 72.15) and serology negative first-degree relatives (67.7% vs 58.3%) (p&lt;0.001). A strong association of DQA1*0501 and DQA1*0301 alleles was observed with high serology positivity (p&lt;0.05). The majority of the subjects in our cohort had histopathologic scores of 3c (54.80%), 3b (22.13%), 3a (22%) and grade 2 (1.05%) (p&lt;0.001). HLA DQB1*0201 was observed as 100% in cases with Marsh grade 2, 72.5% in grade 3a, 82.7% in grade 3b and 85.6% in grade 3c (p=0.017) mucosal lesions. HLA DQA1*0501 and DQB1*0201 alleles of the DQ2 genotype also predicted the severity of intestinal mucosal damage assessed by Marsh grading when used in conjunction with anti-tTG-IgA. When performed in-house using polymerase chain reaction-sequence specific primers method, the assay was economical in identification of mucosal severity in index cases and the first-degree relatives. Its value as a model for additive predictive value in the diagnostic algorithm of cases with tTG-IgA less than 10 times of the upper limit of normal needs further evaluation.

Utility of human leukocyte antigen DQ2 and DQ8 genotypes in Celiac disease: Two sides of the coin

Human Leukocyte Antigen (HLA) DQ2 and DQ8 are the known risk genotypes for Celiac Disease. Diagnosis of celiac disease requires serology testing and intestinal biopsy however, genetic testing could also be implemented because of its high negative predictive value. Our study, initiated prior to the publication of 2020 guidelines, evaluated the utility of HLA DQ2 and DQ8 genotyping in the cohort of 537 children with celiac disease and their 1420 first-degree relatives. We attempted to evaluate its applicability in low-middle-income countries like India. Prevalence of celiac disease was observed at 18.52% and 15.68% based on serological and histopathological diagnosis in first-degree relatives. HLA DQA1*0501 and DQB1*0201 alleles were the most frequently observed alleles in index cases (84.4% versus 86.4%), biopsy proven first-degree relatives (77.9% vs 72.15) and serology negative first-degree relatives (67.7% vs 58.3%) (p&lt;0.001). A strong association of DQA1*0501 and DQA1*0301 alleles was observed with high serology positivity (p&lt;0.05). The majority of the subjects in our cohort had histopathologic scores of 3c (54.80%), 3b (22.13%), 3a (22%) and grade 2 (1.05%) (p&lt;0.001). HLA DQB1*0201 was observed as 100% in cases with Marsh grade 2, 72.5% in grade 3a, 82.7% in grade 3b and 85.6% in grade 3c (p=0.017) mucosal lesions. HLA DQA1*0501 and DQB1*0201 alleles of the DQ2 genotype also predicted the severity of intestinal mucosal damage assessed by Marsh grading when used in conjunction with anti-tTG-IgA. When performed in-house using polymerase chain reaction-sequence specific primers method, the assay was economical in identification of mucosal severity in index cases and the first-degree relatives. Its value as a model for additive predictive value in the diagnostic algorithm of cases with tTG-IgA less than 10 times of the upper limit of normal needs further evaluation.

Assessment of diagnostic value of HLA-DQ2/DQ8 typing and anti-tissue transglutaminase antibodies as an alternative to duodenal biopsy in pediatric celiac disease

Introduction/Objective. The objective of the paper is to assess the applicability of serum anti-tissue transglutaminase (tTG) antibodies IgA and IgG concentration and HLA-DQ2/DQ8 typing as a non-invasive alternative to duodenal biopsy in diagnosing celiac disease (CD) in pediatric population. Methods. A prospective cohort study included a total of 179 pediatric patients aged 1?18 years. Determination of tTG IgA and tTG IgG antibodies and human leukocyte antigen (HLA) DQ2/DQ8 typing was performed for all patients. Histology of duodenal biopsies was interpreted by the modified Marsh scoring system. Results. The diagnosis of CD was confirmed in 101 (56%) patients of the studied population. In cases of CD, HLA-DQ2/DQ8 was positive in 100 patients (99%). The tTG IgA antibodies in concentration higher than 100 U/ml were detected in 77 (76.2%) of the CD patients and in significantly smaller number for tTG IgG [29 (28.7%)] (p &lt; 0.001). Statistically highly significant association of duodenal lesions Marsh grade 3 with concentration of tTG IgA 10-fold higher than the upper level of normal (ULN) was established (p &lt; 0.001) Conclusion. Concentration of tTG IgA 10-fold higher than ULN is significantly positively correlated with Marsh grade 3 histopathology findings. Specific antibodies determination in combination with HLA-DQ2/ DQ8 typing proves to be sufficient for a diagnosis of CD, supporting the fact that duodenal biopsy may be avoided in a significant majority of patients ? 75%.

Identification of celiac disease associated IgA nephropathy by IgA anti-tissue transglutaminase2 antibody deposits in archived formalin-fixed tissues.

The causal association between IgA nephropathy (IgAN) and celiac disease (CeD) is based on their clinical coexistence. In this prospective study, we screened patients with IgAN for CeD and explored the utility of analysis of IgA anti-TG2 antibody deposits, for establishing a causal association. Biopsy-proven patients of IgAN were screened for serum IgA anti-tissue transglutaminase antibody (IgA anti-tTG Ab) titer and thereafter were invited to undergo endoscopic duodenal biopsy. Corresponding duodenal and kidney biopsies were subjected to IgA anti-TG2 antibody colocalization study using dual-color immunohistochemistry and immunofluorescence techniques. Additionally, kidney biopsies from 105 patients with IgAN who did not give consent for serology analysis, 30 non-IgA nephropathies, and 10 normal controls were also included. Dual-color-stained slides were interpreted based on stain distribution and intensity scores, and Pearson's index >0.3-1 on confocal imaging was considered significant. Of a cohort of 151 patients with IgAN, 32 consented to undergo sero-screening and 5 of them had high serum anti-tTG Ab titer. Two out of the latter consented to endoscopic duodenal biopsies, in whom modified Marsh grade 3b changes were identified. Strong IgA anti-TG2 antibody deposits were noted in the kidney and duodenal biopsies of these patients. One patient out of non-consenting 105 patients with IgAN and 3 out of 30 patients with other non-IgA nephropathies also showed IgA anti-TG2 deposits. None of the healthy kidney tissues showed IgA anti-TG2 Ab deposits. Co-localized IgA anti-TG2 deposits in the kidney biopsies in patients with IgAN help to establish a pathogenic link with CeD. A small proportion of patients with IgAN have associated CeD.

Celiac Disease Diagnosis Via Histopathological Correlation of Duodenal Biopsies in Children

Aim: The purpose of this study is to compare the diagnostic accuracy of duodenal bulb biopsies to distal duodenal biopsies in patients suspected of having celiac disease. Study Design: Cross-sectional study Place and Duration: This study was conducted at Department of Pathology, The children's hospital &amp; The institute of child health, Multan during the period from April, 2022 to September, 2022. Methods: Total 86 children of celiac disease were presented in this study. Informed written consent provided by parents of children for the collection of detailed demographic data. Under general anaesthesia, a duodenal bulb sample and four distal duodenum samples were collected during an upper gastrointestinal endoscopy. Histological alterations indicative with CD were identified. Histological diagnosis and grading were performed using a modification of the Marsh-Oberhuber classification. The entire data set was analyzed by using SPSS 20.0. Results: Forty nine (56.97%) patients were females and 37 (43.03%) cases were males. Children’s mean age was 6.4±3.27 years with mean weight 15.9±6.19 kg. Mean height of the cases was 94.7±10.42 cm. There were 51 (59.3%) children had urban residency. According to marsh grading, 50 (58.1%) cases had grade IIIC. We found that frequency of crypt hyperplasia, influx of immune cells in lamina propria and enterocytes change in both duodenal bulb and distal part biopsies were equal while only frequency of villous atrophy and intraepithelial lymphocytes were different in both biopsies. 96.5% patients reported a high level of correlation, while only 3.5% reported no correlation. Conclusion: Both biopsy sites agree strongly. We may now suggest duodenal bulb biopsy alone. Since the endoscopic method of distal duodenum is laborious and requires more knowledge and time, obtaining biopsies from the proximal section is easier and requires less experience, therefore this strategy may be used even at facilities with junior paediatric gastroenterologists. Keywords: Celiac disease, Children, Histopathology, Duodenal bulb, Distal duodenum

Bi-directional Relationship Between Celiac Disease and Liver Chemistries: A Systematic Review and Meta-Analysis.

Previous studies have reported conflicting results regarding prevalence of elevated LC (2-70%) in celiac disease (CD). This systematic review and meta-analysis assessed the prevalence of elevated LC at time of CD diagnosis and associated response to GFD. We also report the prevalence of CD in patients with unexplained elevation of LC. Studies assessing LC (aspartate aminotransferase [AST] and alanine aminotransferase [ALT]) in CD patients were eligible. Studies with < 50 cases or in pediatric populations were excluded. In total, 20 studies assessing prevalence of elevated LC in 4,265 participants with newly diagnosed CD (mean age = 35.6 ± 6.5years, 69.8% female) were included. Pooled prevalence of elevated LC was 18.7% (95% CI 13.8-24.8; I2 = 95%). Normalization of elevated LC was seen in 83.1% (95% CI 73.4-89.7; I2 = 79%, 11 studies) of patients after GFD. On meta-regression, age at CD diagnosis, gender, and Marsh grading were not associated with elevated LC. Among 979 participants (7 studies) with unexplained elevation of LC, pooled seroprevalence and biopsy-proven CD was 6.4% (95% CI 2.9-10.3, I2 = 71%) and 4.5% (95% CI 2.6-7.7, I2 = 67%), respectively. Elevated LC are seen in approximately one-fifth of patients at CD diagnosis with majority normalizing after GFD. Age, gender, and degree of intestinal damage are not predictive of elevated LC. In the appropriate clinical scenario, liver tests should be serially monitored in CD reserving workup for additional causes after a trial of GFD. Patients with unexplained elevation of liver tests should be screened for celiac disease.

The development and validation of a high-capacity serological assay for celiac disease

BackgroundThe aim of the present study was to develop and clinically validate a high-throughput assay for serum IgA and IgG antibodies against transglutaminase-2 (TG2) and to determine appropriate assay cut-offs for large-scale population screening for celiac disease. MethodAn automated method was developed using dual label time-resolved fluorometry on the AutoDELFIA platform. Individuals (n = 1920) from the general population were screened. Subjects with serum anti-TG2 concentrations above a preliminary cut-off (>0.3 mg*/L anti-TG2 IgA or >0.5 mg*/L anti-TG2 IgG) were offered endoscopic examination and biopsy. A diagnosis of celiac disease was given if villous atrophy (Marsh grade 3) was found. ResultsThe assay had a limit of quantification of 0.25 mg*/L (anti-TG2 IgA) and 0.60 mg*/L (anti-TG2 IgG) with imprecision (CV) < 16% and <18% respectively. A total of 66 individuals were above the preliminary cut-off, and 56 underwent endoscopy. Of these, 26 were diagnosed with celiac disease. Sixty-eight percent of subjects with anti-TG2 IgA ≥ 0.7 mg*/L or anti-TG2 IgG ≥ 1.0 mg*/L had biopsy-proven celiac disease, and utilization of these higher cut-offs identified 96% of biopsy-positive patients. At the time of endoscopy, all individuals with anti-TG2 IgA > 2.0 mg*/L had celiac disease, and this cut-off identified 88% of newly diagnosed celiac patients. Eight percent (2/26) of the newly diagnosed patients had primarily anti-TG2 IgG. ConclusionsIn this study we developed and clinically validated a robust and automated assay suitable for celiac disease screening in the general population.

A Multicenter Cross Sectional Study to Evaluate the Role of Duodenal Bulb Biopsy in the Diagnosis of Celiac Disease

Background and Aim: A systemic immune disorder elicited by dietary gluten in people who are genetically predisposed to it is referred to as a celiac disease. D1 had been ruled out as a biopsy site due to concerns about Brunner's glands, peptic duodenitis, gastric metaplasia, and presumed reduced villous height. Due to histological confounding factors, the duodenal bulb (D1) as a biopsy site was traditionally avoided. The present study aimed to assess the duodenal bulb biopsy role in the diagnosis of celiac disease. Methodology: This multicenter cross sectional study was conducted on 108 celiac disease patients in the department of Gastroenterology, Bacha Khan Medical Complex, Swabi, North West General hospital Peshawar and Pir Abdul Qadir Shah Jilani Institute of Medical Science Gambat Khairpur, Sindh from September 2020 to July 2021. All the celiac disease patients were clinically symptomatic and had anti-tissue transglutaminase (anti TTG IgA) positive antibodies. Endoscopically, six mucosal biopsies were taken from each patient, four each from the distal duodenum and two additional biopsy separately labelled was taken from bulb. Modified Marsh grading was used for morphological grading. Results: Of the total 108 Celiac disease patients, 60 (55.6%) were females and 48 (44.4%) were male patients. the overall mean age was 32.62±6.4 years. Prior to diagnosis of Celiac disease, symptoms median duration was 5.4 years with a range of 6 months to 40 years. The most prevalent clinical presentation were iron deficiency anemia 43% (n=46) and chronic diarrhea 32% (n=35) respectively. Other clinical presentation were chronic pain abdomen, infertility, short stature, and cirrhosis. Elevated TTG of 117.1 ± 49.82 U/ml was measured in all the patients with a range of 20 to 250 U/ml. The incidence of similar and different modified Marsh grade was in 66 (61.1%) and 42 (58.9%) respectively at both site. Out of 42 different modified March grade patients, higher mucosal atrophy in bulb and descending duodenum showed higher grade in 16 and 26 patients respectively. Isolated bulb involvement was seen in nine patients. Due to bulb biopsy, Celiac disease diagnosis was correctly done in these patients. Conclusion: The present study supported the villous atrophy and intraepithelial lymphocytosis patchy nature in biopsy specimens of celiac disease. The diagnosis of celiac disease improved with inclusion of duodenal bulb biopsies in our sampling protocol. Celiac disease patchy nature and distribution demonstrated different Marsh grades in different biopsy sites. The celiac disease diagnostic yield is increased by combining the bulb and the descending duodenum biopsy. Keywords: Celiac Disease, Duodenal bulb biopsy, Modified Marsh grade

Zonulin and I-FABP are markers of enterocyte damage in celiac disease

To evaluate the level of serum I-FABP (Fatty-Acid-Binding Protein a protein that binds fatty acids) and fecal zonulin as markers of the permeability of the mucous membrane of the small intestine in celiac patients. A total of 151 celiac patients (25 men and 126 women) were examined. The median age was 42 years. Group I included 58 patients with newly diagnosed celiac disease; in group 2 38 patients, knowingly or unknowingly violating the gluten-free diet; group 3 consisted of 55 patients strictly observing gluten-free diet. The control group consisted of 20 healthy volunteers: 4 men and 16 women. All patients underwent esophagogastroduodenoscopy by biopsy of the mucous membrane of the small intestine and assessment of duodenobioptates according to Marsh. In the blood serum, the level of antibodies to tissue transglutaminase IgA and IgG was determined by the enzyme-linked immunosorbent assay using kits manufactured by Orgentec Diagnostics GmbH (Germany), the concentration of I-FABP in blood serum was determined using Hycult Biotech kits (Netherlands). The content of zonulin in feces was investigated by enzyme-linked immunosorbent assay using kits from Immundiagnostik AG (Germany). Statistical analysis was performed using the Statistica 13.3 software (StatSoft Inc., USA). There was a significant increase in the level of antibodies to tissue transglutaminase IgA [120.0 (41.1200)] IU/ml and IgG [31.4 (5.578.9)] IU/ml in patients of group 1 compared with group 2 [IgA 9.1 (2.987.6)] and IgG [3.8 (2.219.7)] IU/ml and group 3 [IgA 1.6 (1.03.2)] and IgG [2.2 (1.152.53)] (p0.01). The level of I-FABP in blood serum in patients of group 1 averaged 2045 pg/ml, in patients in group 2 1406 pg/ml, in patients in group 3 1000 pg/ml. All patients showed a significant increase in the mean I-FABP values compared to controls (1, 2 and control p0.01, 3 and control p=0.016). In patients with Marsh grade III AC atrophy, the I-FABP level depended on the degree of damage to the mucosa and significantly differed from the control: March IIIA (median: 1310 pg/ml, interquartile range: 12121461 pg/ml), March IIIB (median: 2090 pg/ml, interquartile range: 18122322 pg/ml) as well as Marsh IIIC (median: 2058 pg/ml, interquartile range 18582678 pg/ml). The concentration of zonulin in feces in patients of group 1 averaged 111.6 pg/mg, in patients of group 2 90.5 pg/mg. In patients of group 3 50 IU/ml. The concentration of zonulin in feces increased as the degree of mucosa atrophy increased (r=0.585, p0.01). However, despite the fact that both of these markers may indicate impaired permeability, each of them indicates damage to a certain level of the intestinal barrier, which is not always associated with the degree of mucosa atrophy. Determination of serum I-FABP and fecal zonulin levels in celiac patients allows for the assessment of intestinal permeability and can serve as non-invasive markers for monitoring ongoing structural changes in the mucosa without the need for endoscopy.

Evaluating the Correlation between High Titers of Tissue-Transglutaminase Antibody with the Grade of Severity of Villous Atrophy in Syrian Patients with Celiac Disease

Background. Diagnosis of celiac disease depends on the patient’s history and serological tests, and is confirmed by biopsies from the duodenum. Biopsies from the small intestine could be dispensable regarding the verification of celiac disease with the presence of high levels of atissue-transglutaminase antibody.Aim. The objective of this investigation is to substantiate the correlation between titers of anti-tissue transglutaminase type IgA (anti-tTG IgA) and the severity of histological alterations in Syrian patients with celiac disease and to determine the diagnostic level of anti-tTG to previse celiac disease in adults and children without the necessity of a biopsy sampling.Materials and methods. The study was conducted as a prospective cohort study with the participation of 100 symptomatic patients between the age group of 6–65 years. All participants underwent upper gastrointestinal endoscopy. Two samples were taken from the duodenum and were evaluated by an expert pathologist according to Marsh grading. Serum anti-tTG IgA levels were measured as well to determine any association between the levels of serum anti-tTG IgA and Marsh grading.Results. The mean age of the patients was (18.55 ± 12.92). Anemia was the most frequent non-gastrointestinal finding as it was found among 35% of the participant, but no remarkable association was found between Marsh grading and hemoglobin levels (r = 0.36, p &gt; 0.05). However, serum tTGA levels were positively correlated with Marsh grading (r = 0.718, p &lt; 0.001). Receiver-operator curve (ROC) analysis cut-off value of serum anti-tTGA for speculating villous atrophy was 270 IU/ml of cut-off value with a sensitivity of 100% and a specificity of 89%.Conclusion. Duodenal biopsies could be foregone during the diagnosis of susceptible patients for celiac diseasewith high anti-tTG IgA.

Epidemiological, clinical, and histological presentation of celiac disease in Northwest China.

BACKGROUNDResearch on celiac disease (CD) in northwest China is still in its infancy. At present, large-sample data on the epidemiological, clinical, and pathological characteristics of CD are limited.AIMTo investigate the epidemiological, clinical, and pathological characteristics of CD in northwest China.METHODSThe clinical data of 2884 patients with gastrointestinal (GI) symptoms were retrospectively analyzed. Total immunoglobulin A (IgA) and anti-tissue transglutaminase (tTG) IgA levels were examined in all patients. Gastroscopy and colonoscopy were performed in patients with positive anti-tTG IgA and deficient total IgA levels. Atrophy of the duodenal and ileal villi was examined and histopathological examinations were performed. The modified Marsh–Oberhuber classification system was used to grade villous atrophy in the duodenum or distal ileum. The patients’ Helicobacter pylori (H. pylori) infection status was compared in terms of clinical presentation and Marsh grade. Statistical analyses were performed using the t-test or chi-square test.RESULTSAmong the 2884 patients, 73 were positive for serum anti-tTG IgA, and 50 were diagnosed with CD. The CD detection rate was significantly higher in Kazakhs (4.39%) than in Uyghurs (2.19%), Huis (0.71%), and Hans (0.55%). The main symptoms of CD were chronic diarrhea, anorexia, anemia, fatigue, weight loss, sleep disorders, osteopenia, and osteoporosis. The body mass index of patients with CD was significantly lower than that of patients without CD. A total of 69 patients with positive serum anti-tTG IgA and two patients with deficient total IgA levels underwent GI endoscopy. Endoscopy revealed crypt hyperplasia and/or duodenal villous atrophy, mainly manifested as nodular mucosal atrophy, grooves, and fissures. The difference in H. pylori infection rates was not statistically significant between CD and non-CD patients but was significantly different among CD patients with different Marsh grades.CONCLUSIONAmong the patients with GI symptoms in northwestern China, the prevalence of CD was more in the Uyghur and Kazakh populations. H. pylori infection may be associated with CD severity.