Transglutaminase IgA Antibodies Research Articles

Correlation between auto-immune diseases and type 1 diabetes mellitus in the pediatric age group in Erbil city

Background and objective: Type-1 diabetes mellitus is the most common chronic endocrine disorder of childhood and adolescence and is characterized by immune-mediated destruction of pancreatic cells, which has been proven to be correlated with and increase the risk of developing autoimmune thyroid disease, celiac disease, Addison’s disease, and further autoimmune diseases. The aim of this study is to evaluate the prevalence of autoimmune disease-related markers in type 1 diabetes mellitus in children and adolescents in Erbil city. Methods: One hundred children and adolescents with type 1 diabetes mellitus were enrolled in this cross-sectional study. Patients <1 year old were excluded from the study. Autoimmune thyroid antibodies (anti-thyroid peroxidase and anti-thyroglobulin) along with tissue transglutaminase (IgA and IgG) antibodies were measured with further evaluation by thyroid function test and endoscopy with biopsy (for positive serological autoantibodies level). Results: Elevated anti-thyroglobulin, anti-thyroid peroxidase, and tissue transglutaminase IgA and IgG antibodies were determined in 24.0%, 26%, 10%, and 8%, respectively. 50.0% of cases with positive anti-thyroid peroxidase antibodies had overt hypothyroidism; on the flip side, 3.8% had subclinical hypothyroidism. As well, the high level of thyroid autoantibodies was significantly correlated to the prevalence of overt hypothyroidism (P <0.001). Nine of the patients with positive tissue transglutaminase antibodies were verified to have biopsy-proven celiac disease. Conclusion: Children and adolescents with type 1 diabetes mellitus are at risk of developing positive antithyroid and celiac-related autoantibodies, so they are at risk of progressing to autoimmune thyroid and celiac diseases.

Case report: Multiple autoimmune syndrome

This is a case of multiple autoimmune syndrome with the co-occurrence of vitiligo, pernicious anemia, celiac disease and autoimmune hepatitis is extremely rare. We are presenting a case is a 40-year-old woman with autoimmune hepatitis who is suffering from poor appetite, weight loss and skin lesions. Laboratory investigation shows hypochromic microcytic anemia, B12, and iron deficiency. The testing for parietal cell antibody was positive so pernicious anemia was diagnosed with positive Tissue transglutaminase antibody IgA so the diagnosis of celiac disease was confirmed.

Celiac Disease in Moroccan Children: Diagnostic Characteristics and Determinants of Diagnosis Delay.

Advances in the field of celiac disease have led to a better understanding of the disease, but it remains underdiagnosed and poses a daily challenge to clinicians to make a timely diagnosis. This study aims to analyze and describe diagnosis characteristics, diagnosis delay, and the factors influencing this delay in Moroccan children. Our study included 324 children diagnosed during the study period from January 01, 2010, to December 30, 2019, at the Department of Pediatrics, Hassan II University Hospital inFez, Morocco. Data were collected using a collection grid and then analyzed using SPSS 26 software (IBM Corp., Armonk, NY). The results showed a female predominance (n=197, 60.8%), with a diagnosis age of 73.8±46.8 months. The mean age onset of symptoms was 51.3±41.2 months, and the diagnosis delay was 22.2±22.6 months, with only 32.7% (n=106) diagnosed less than 12 months after symptom onset. The most common consultation reason was diarrhea (n=149, 46%) and growth delay (n=105, 32.4%) and 50.5% (n=98) of parents consulted a pediatrician first. The three clinical, serologic, and histologic criteria made it possible to agree on the diagnosis, with the clinical profile dominated by the digestive form at 84.9% (n=279), serologic with the presence of IgA transglutaminase antibodies (95.7%; n=310), and histologic with villous atrophy at 91.7% (n=297). Unfortunately, 14.8% (n=48) of the children were diagnosed with a celiac crisis. The multivariate logistic regression analysis showed that as symptoms onset age increased, so did the risk of late diagnosis (OR=0.96, 95% CI: 0.94 to 0.97, p<0.001). Age of diagnosis was also associated with delayed diagnosis (OR=19.68, 95% CI: 8.77 to 44.15, p<0.001). The combination of these variables and the diagnosis delay argues in favor of adopting a diagnosis strategy that includes raising awareness among healthcare professionals of the need to identify typical and atypical cases early in order to reduce the adverse effects of late diagnosis and the complications that can result. This methodology for improving diagnoses may also unearth previously unknown aspects of celiac disease in Moroccan children.

Do Serological Tests Eliminate the Need for Endoscopic Biopsy for the Diagnosis of Symptomatic Patients with Celiac Disease? A Retrospective Study with Review of Literature.

Background: Celiac disease is one of the most common genetic allergies worldwide. The prevalence of celiac disease in Iran is similar to or even higher than the global prevalence. Celiac disease is a chronic inflammatory disease that affects the small intestine. Affected patients are allergic to gluten protein that exists in some grains, such as wheat and barley. Methods: Serological endomysial IgA antibody (EMA-AB) and tissue transglutaminase IgA antibody (TTG-IgA) tests were performed on 114 patients aged the ages of 0-18 years with histopathological findings of celiac disease. The results of these tests were compared to the results of the histopathological study of the duodenal biopsy. Results: Based on the receiver operating characteristic (ROC) curve and a calculation of the TTG-IgA test's sensitivity and specificity, the best diagnostic limit for the TTG-IgA test is 144, which has the best sensitivity and specificity. At this value (cut-off), the test's sensitivity was 62%, and the specificity was 93.7%. For the endomysial test, sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were 80%, 93%, 90%, and 75%, respectively. Conclusion: The diagnostic accuracy of the endomysial test is better than that of the TTG-IgA test in general for diagnosing patients with celiac disease. In the TTG-IgA test, false-positive cases are high due to a cut-off of 20, reducing the test's specificity. In these false-positive cases, the endomysial test helps in better diagnosis.

Helicobacter Pylori and Celiac Disease Antibody Positivity Have a Higher Prevalence in Patients With Distal Gastrectomy: A Cross-Sectional Retrospective Study.

Aims and objectives Distal gastrectomy was a widely used therapeutic option for peptic ulcer and gastroesophageal reflux disease until quite recently. The consequences of anatomical and physiological changes following surgery in the gastric mucosa have been the object of interest for the scientist. In this study, we aimed to determine whether Helicobacter pylori (HP) infection and celiac disease were more common in patients with a history of distal gastrectomy. Materials and methods This is an observational retrospective study conducted at Giresun University Faculty of Medicine. The medical files of 35 patients with dyspepsia who had a history of distal gastrectomy for benign etiologies (antrectomy group) and 50 patients with dyspepsia (control group) were retrospectively analyzed. Results There were more males and older patients in the antrectomy group. Concerning the lab parameters, platelets, lymphocyte, and albumin levels were significantly lower, and urea, creatinine, anti-Endomisium Ig A (anti-EMA), and anti-tissue transglutaminase IgA (anti-tTGA) antibody positivity were significantly higher in the antrectomy group. Gastric biopsy results revealed a higher positivity of HP, atrophy, neutrophil, and lymphocytes in the antrectomy group. Correlation analysis revealed an inverse correlation between albumin and anti-EMA/atrophy positivity whereas a positive correlation between anti-EMA and HP/atrophy positivity. Conclusions HP infection and coeliac disease (CD) could be the problems that distal gastrectomy patients with dyspepsia can face during their follow-up. Concerning the pre-malignant potential of HP, its screening and eradication should be performed to prevent the malignant transformation of the remnant gastric tissue.

Vitiligo and anti-tissue Transglutaminase of celiac disease in Al- Nasiriyah city, Iraq

Vitiligo is acquired pigmentation disorder characterized by sharply defined white spots of irregular shape and variable dimensions, increasing in volume and number over time. The causes of vitiligo are still unknown. But it involve some theories like autoimmunity, this study was aimed to detection the relationship between the vitiligo and celiac disease by investigating the presence of celiac tissue transglutaminase IgA(tTGA) autoantibody in patients of vitiligo by using ELISA technique . The study was conducted on 100 patients with vitiligo and 100 healthy individual as control , the mean age of vitiligo patient was 19.4 year and control was 26.3 year .The results of study were showed , twenty six of cases have family history of vitiligo , 53 of cases have family history of other autoimmune disorders, as well as 4 of cases have positive family history of vitiligo with diabetes and thyroid disorders. Tissue transglutaminase IgA antibody test was showed ,12 out of 100 of vitiligo cases were registered Seropositivity result to tTGA antibody, while 4 out of 100 of control were Seropositive to this antibody ,other cases and control were negative for IgA antibody.

Coeliac Disease Case–Control Study: Has the Time Come to Explore beyond Patients at Risk?

The worldwide prevalence of asymptomatic coeliac disease (CD) is increasing, which is in part due to the routine screening of children with risk factors. Both symptomatic and asymptomatic patients with CD are at risk of long-term complications. The objective of this study was to compare the clinical characteristics of asymptomatic and symptomatic children at the time of CD diagnosis. A case-control study was conducted using data from a cohort of 4838 CD patients recruited from 73 centers across Spain between 2011 and 2017. A total of 468 asymptomatic patients (cases) were selected and matched by age and sex with 468 symptomatic patients (controls). Clinical data, including any reported symptoms, as well as serologic, genetic, and histopathologic data were collected. No significant differences were found between the two groups in most clinical variables, nor in the degree of intestinal lesion. However, the asymptomatic patients were taller (height z-score -0.12 (1.06) vs. -0.45 (1.19), p < 0.001) and were less likely to have anti transglutaminase IgA antibodies ≥ 10 times the upper normal limit (66.2% vs. 758.4%, p = 0.002). Among the 37.1% of asymptomatic patients who were not screened for CD due to the absence of risk factors, only 34% were truly asymptomatic, while the remaining 66% reported non-specific CD-related symptoms. Therefore, expanding CD screening to any child who undergoes a blood test could reduce the burden of care for some children, as many of those considered asymptomatic reported non-specific CD-related symptoms.

Early Antibody Dynamics in a Prospective Cohort of Children At Risk of Celiac Disease.

The purpose of this study was to identify possible serum biomarkers predicting celiac disease (CD) onset in children at risk. A subgroup from an ongoing, international prospective study of children at risk of CD was classified according to an early trajectory of deamidated gliadin peptides (DGPs) immunoglobulin (Ig) G and clinical outcomes (CD, potential CD, and CD autoimmunity). Thirty-eight of 325 children developed anti-tissue transglutaminase IgA antibody (anti-tTG IgA) seroconversion. Twenty-eight of 38 children (73.6%) showed an increase in anti-DGPs IgG before their first anti-tTG IgA seroconversion. Anti-DGPs IgG can represent an early preclinical biomarker predicting CD onset in children at risk.

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

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. A range of differential diagnoses have been reported for severe duodenal architectural distortion. 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. 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. 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.

Characteristics of Pediatric Celiac Disease in Southern West Virginia

Purpose Celiac disease (CD) is a disorder in which gluten ingestion triggers an autoimmune response causing inflammation and damage to the small intestine. With improved awareness and screening availability, prevalence and variation in clinical presentation have subsequently increased. Thus, our study identified the disease characteristics and presentation patterns of pediatric CD in southern West Virginia. Methods We retrospectively reviewed charts for pediatric patients (age &lt;18 years) diagnosed with CD during a 10-year period at a tertiary care hospital. Results A total of 59 patients met inclusion criteria. The mean age of diagnosis was 10.0+4.6 years, with 61% of patients being female. One-third of cases were asymptomatic and diagnosed from screenings of patients with hypothyroidism or type 1 diabetes mellitus. In symptomatic patients (n=40), abdominal pain was the most common presenting symptoms (78%), followed by constipation (30%). Classical symptoms of diarrhea and failure to thrive/unexplained weight loss were less common (n=9). At diagnosis, anti-tissue transglutaminase (tTG) IgA antibodies and deamidated gliadin peptide IgG antibodies were both positive in 88% of cases, and endomysial antibodies were positive in 70% cases. One-year post-diagnosis clinic follow-up rate was 63%. A gluten-free diet improved symptoms and tTG IgA serology levels in all patients with follow-up. Conclusion Our data fills in the gap of the paucity of information available about CD in children from Appalachia. A high index of suspicion is required to screen and diagnose CD as many patients are either asymptomatic or lack classical findings. A gluten-free diet is a highly effective treatment, although follow-up after initial diagnosis remains a challenge.

İlaç alerjisi olan hastalarda otoantikor sıklığı

Introduction: This study is aimed to analyze the autoantibody frequency in patients with drug allergy. Descriptive, observational research on drug allergy will contribute to the creation of new hypotheses about the pathophysiology of autoimmunity.Methods: The data of patients who were registered in the Training and Research Hospital database until the end of December 31, 2018 and diagnosed with drug allergy were retrospectively evaluated. Overall, 617 adult patients who had been diagnosed as “allergy status to drugs,” according to ICD 10, and had had at least one autoantibody result were included in the study.Results: The frequency of having at least one autoantibody varied between 0% and 92.1%. The most commonly detected autoantibody was rheumatoid factor (RF) (n = 241; 92.1%). The second most common one was anti-tissue transglutaminase IgA antibody (Anti-tTG-IgA) (n=22; 68.2%). The frequencies of anti-thyroglobulin (Anti-TG), anti-thyroid peroxidase (anti-TPO), and anti-double stranded DNA (Anti-dsDNA) were 65.2% (n = 155), 59.7% (n = 159), and 43.6% (n= 55), respectively.Conclusions: Many drugs can trigger the development of autoantibodies with no progression to autoimmune disease. Autoantibodies should be suspected in patients with allergies to medications. Observational research on drug allergy will contribute to the creation of new hypotheses about the pathophysiology of autoimmunity. Numerous studies in this area can enable us to discuss the widespread use of risky drugs in a more objective way. We think that our study will shed light on the relationship between drug reaction and autoimmune diseases.Keywords: Autoantibodies, autoimmunity, drug allergy, drug hypersensitivity

"Long-term follow-up and prognosis of celiac hepatitis".

Celiac disease has been associated with abnormal liver function tests at diagnosis that usually resolve with a gluten-free diet (GFD). The aim of this study was to assess the evolution of liver involvement and possible long-term complications in patients on a GFD. Retrospective and single-center study, which included all individuals with Celiac disease followed in specialized consultation in a tertiary referral hospital. A total of 162 patients were included, most of them female (77.8%) with a median age of 24 years (IQR, 7-39). Seventy-four (45.7%) patients had abnormal liver function tests at diagnosis. These individuals had higher anti-tissue transglutaminase IgA (tTG-IgA) antibody titers (126 vs. 29 IU/L; P = 0.003). There were no significant differences in the Marsh classification ( P = 0.599). During follow-up, most celiac hepatitis patients had normalization of liver function tests and tTG-IgA antibodies. At the last follow-up, all the patients had fibrosis-4 index &lt;2.4 and an aspartate aminotransferase-to-platelet ratio index score &lt;0.6. Vibration-controlled transient elastography showed values &lt;6.4 kPa in all cases. On the other hand, it was found that 42.9% of the individuals had a controlled attenuation parameter &gt;206.5 db/m. In our cohort, liver function tests normalized in the vast majority of celiac hepatitis patients on a GFD, with no progression to chronic liver disease. It should be noted the high number of individuals who present hepatic steatosis during follow-up, which may be related to a diet that tends to be hyperlipidemic and hypercaloric.

Estimation of serum iron, serum lipids and serum liver enzymes in celiac disease patients of Saudi Arabia

To evaluate the serum biochemical levels in celiac disease (CD) patients. It was a cross-sectional study carried out on 70 subjects, including 40 patients with CD and 30 healthy controls. This study was conducted at Jouf University from November, 2020 to October, 2021. The collected blood specimens were used to perform serum iron, serum lipids, liver enzymes, and human tissue transglutaminase IgA antibodies (anti-HTTG). The hematological parameters including hematocrit and MCV were determined to establish the diagnosis of iron deficiency. Serum iron was significantly lower in patients as compared to the controls. Serum iron, serum HDL, blood hematocrit and MCV were significantly lower in patients than in controls (p = 0.000). Serum levels of liver enzymes (ALT and AST) and serum human tissue transglutaminase antibodies (anti-HTTG) were significantly higher in patients than in controls (p = 0.000). The correlation studies established the negative correlation of anti-HTTG IgA with serum iron (r = -0.991, p = 0.000), hematocrit (r = -0.967, p = 0.000) and MCV (r = -0.946, p = 0.000) in patients. The serum iron was remarkably reduced in CD patients. A negative correlation was found between anti-HTTG IgA and serum iron, while a positive serum iron was correlated with hematocrit and MCV in CD patients.

Diagnostic Accuracy of Serum Anti-Tissue Transglutaminase Antibody in Diagnosis of Pediatric Celiac Disease

Background: Celiac disease (CD) is an immune mediated enteropathy that is caused by intolerance to gluten storage protein of wheat bartey and rice. Early diagnosis of celiac disease is highly imperative to institute early intervention in order to prevent profound macronutrient deficiencies as well as long term complications. Diagnostic investigation for celiac disease, the matter of controversy, with endoscopic duodenal biopsy remaining the gold standard but invasive, costly, painful, needing expertise and carrying risks of endoscopy, while serologic tests although noninvasive, cheap, easily available but with disputed specificity and sensitivity. Objective: To find the accuracy and importance of anti-tissue transglutaminase IgA antibody in celiac disease diagnosis and determination in pediatric patients. Place and Duration of Study: Department of Pediatrics, GMMMC Hospital Sukkur from 1st June 2019 to 30th November 2019. Methodology: One hundred and fifty children were suspected celiac diseases were enrolled. Demographic data including age, gender was noted. Duodenal biopsy and upper GI endoscopy of all patients with positive anti-tTG was performed. At least 6 biopsy specimens were taken from first and second part of duodenum and duodenal bulb. Results: Mean age of the children was 8.72±1.92 years. Sensitivity, specificity, PPV and NPV of tTG-IgA in evaluating celiac disease was 86.9%, 84.8%, 88%, 83.6% and 86% respectively. Conclusion: Tissue transglutamianse (TTG) is an excellent screening test for celiac disease in high risk Paediatric population having diagnostic accuracy of 86%. Therefore, it can be safely recommended that patients having even fewer clinical features should be screened by TTG to detect celiac disease patients with minimal signs and symptoms. Keywords: Celiac disease, IgA anti-tissue transglutaminase, Gastrointestinal endoscopy

No-biopsy strategy for coeliac disease is applicable in adult patients: a ‘real-world’ Scottish experience

ObjectiveEmergency interim guidance from the British Society for Gastroenterology (BSG) states that a no-biopsy strategy is possible to diagnose coeliac disease (CD) in adults with elevated transglutaminase IgA antibody (TGA-IgA)...

The Prevalence of Associated Autoimmune Diseases Among Adults With Type 1 Diabetes Mellitus: A Cross-Sectional Study

BackgroundThe relationship between type 1 diabetes mellitus (T1DM) and other autoimmune diseases has been known; however, the actual prevalence in the adult population nor clinical symptoms has not been determined locally.ObjectivesWe aim to determine the prevalence of associated autoimmune diseases (Hashimoto’s thyroiditis, celiac disease (CD), and adrenal insufficiency (AI)) and evaluate the most reporting symptoms and glycemic control assessment, as well as microvascular complications and hypoglycemia episodes.MethodsA cross-sectional study of 251 patients with T1DM at the diabetic clinic of King Abdulaziz Medical City in Riyadh (KAMC-RD), Saudi Arabia, was conducted. Autoimmune serologies including thyroid peroxidase (TPO) antibody and tissue transglutaminase IgA (tTG-IgA) antibody were checked with hormonal studies such as thyroid-stimulating hormone (TSH), morning serum cortisol, and short Synacthen test (SST) with duodenal biopsy results all were reviewed if present. Patients were directly interviewed to evaluate for the most common symptoms (including hypoglycemia episodes) for the preceding two weeks. Glycemic control was assessed by measuring glycated hemoglobin (HbA1c). Microvascular complications (i.e., nephropathy and retinopathy) were estimated by looking at the urine albumin/creatinine ratio (ACR) besides the ophthalmology’s visit notes.ResultsThe mean age was 26.3 ± 7.7 years, and the mean duration of diabetes at the time of data collection was 12.2 ± 7.6 years, whereas the mean HbA1c was 8.9% ± 1.8%. The prevalence of hypothyroidism was 16.3%, and TPO positivity was discovered in 58.6% of the tested patients (n = 70) with equal prevalence among both genders (p = 0.685). tTG-IgA were noticed among 16.4% of the patients (n = 164) without significant difference among gender. Serum cortisol test was performed among 128 patients; 28.1% had suboptimal levels, and 5.5% were deficient. Only four patients (n = 15) had suboptimal responses after SST. Nervousness and anxiety (p < 0.001), fatigue with weakness (p = 0.018), weight gain (p = 0.017), and cold intolerance (p = 0.005) were noted, which were statistically significantly higher among females. Weight gain was statistically significantly higher among the age group of >30 years (p = 0.036). For microvascular complication screening, ACR was collected in 199 (79.2%) participants, with a mean of 27.7 ± 155.9 mg/mmol. Only 10 (5%) patients had microalbuminuria, and 16 (8%) had macroalbuminuria; it was correlated significantly with diabetes duration (p = 0.045). A total of 132 (52.8%) patients were seen by ophthalmology, 28 (21.4%) had nonproliferative diabetic retinopathy (NPDR), and 10 (7.6%) has proliferative diabetic retinopathy (PDR) that significantly correlated with the duration of diabetes (p = 0.027). During patient interviews, 187 (74.5%) reported symptomatic hypoglycemia events that correlated significantly with glycemic control (p = 0.029).ConclusionAutoimmunity in Saudi adults with type 1 diabetes mellitus was significant with equal prevalence among both genders and age groups with no or slight difference. Clinical manifestations of autoimmunity were higher in women. Diabetes chronicity and poor glycemic control were the major complications; therefore, early glycemic control is advocated. Regular screening for autoimmunity and its complications is recommended for type 1 diabetic patients. Autoimmunity was found almost similar to previous literature.

Frequency of celiac disease and distribution of HLA-DQ2/DQ8 haplotypes among siblings of children with celiac disease.

BACKGROUNDCeliac disease (CD) is a multifactorial disease, but genetic factors play a major role in its etiology. It has been known that human leucocyte antigen (HLA)-DQ2/DQ8 haplotypes are one of the most important predisposing genetic factors. The risk of developing CD in first-degree relatives and especially siblings of celiac patients is quite high because of having the same HLA haplotypes.AIMTo evaluate the frequency of CD and the distribution of the HLA-DQ2/DQ8 haplotypes in siblings of celiac patients.METHODSPatients with biopsy-proven CD and their siblings were included in the study; those who did not have HLA genotyping were excluded from the study. All siblings were on a gluten-containing diet. The HLA genotyping, tissue transglutaminase antibody IgA antibody test, and total IgA test were performed in all participants.RESULTSA total of 57 celiac patients and their 112 siblings were included in the study. The mean age of celiac patients and siblings were 10.30 ± 3.87 years and 9.90 ± 6.11 years, respectively. HLA-DQ2/DQ8 alleles were detected in 98.2% of patients with CD and 90.2% of siblings of celiac patients. HLA-DQ genotypes were present in all siblings diagnosed with CD. Tissue transglutaminase antibody IgA test was found to be positive in 16 siblings. CD was diagnosed in 12 siblings (10.7%) by intestinal biopsy.CONCLUSIONThe prevalence of CD was found to be 10.7% in siblings of celiac patients in our study. One-third of the siblings diagnosed with CD were asymptomatic. We detected HLA-DQ alleles in 98.2% of celiac patients and 100% in siblings diagnosed with CD. In addition, 1 of the 2 siblings was diagnosed with CD 1 year later and the other 4 years later. Therefore, we suggest that siblings of celiac patients should be followed up with clinical findings as well as HLA analysis and serological examination. Since the risk of developing CD is much higher in asymptomatic siblings, we recommend that siblings should be screened for CD even if they are asymptomatic.

Intestinal fatty acid binding protein is a disease biomarker in paediatric coeliac disease and Crohn’s disease

BackgroundThere is a clinical need to develop biomarkers of small bowel damage in coeliac disease and Crohn’s disease. This study evaluated intestinal fatty acid binding protein (iFABP), a potential biomarker of small bowel damage, in children with coeliac disease and Crohn’s disease.MethodsThe concentration iFABP was measured in plasma and urine of children with ulcerative colitis, coeliac disease, and Crohn’s disease at diagnosis and from the latter two groups after treatment with gluten free diet (GFD) or exclusive enteral nutrition (EEN), respectively. Healthy children (Controls) were also recruited.Results138 children were recruited. Plasma but not urinary iFABP was higher in patients with newly diagnosed coeliac disease than Controls (median [Q1, Q3] coeliac disease: 2104 pg/mL 1493, 2457] vs Controls: 938 pg/mL [616, 1140], p = 0.001). Plasma or urinary iFABP did not differ between patients with coeliac on GFD and Controls. Baseline iFABP in plasma decreased by 6 months on GFD (6mo GFD: 1238 pg/mL [952, 1618], p = 0.045). By 12 months this effect was lost, at which point 25% of patients with coeliac disease had detectable gluten in faeces, whilst tissue transglutaminase IgA antibodies (TGA) continued to decrease. At diagnosis, patients with Crohn’s disease had higher plasma iFABP levels than Controls (EEN Start: 1339 pg/mL [895, 1969] vs Controls: 938 pg/mL [616, 1140], p = 0.008). iFABP did not differ according to Crohn’s disease phenotype. Induction treatment with EEN tended to decrease (p = 0.072) iFABP in plasma which was no longer different to Controls (EEN End: 1114 pg/mL [689, 1400] vs Controls: 938 pg/mL [616, 1140], p = 0.164). Plasma or urinary iFABP did not differ in patients with ulcerative colitis from Controls (plasma iFABP, ulcerative colitis: 1309 pg/mL [1005, 1458] vs Controls: 938 pg/mL [616, 1140], p = 0.301; urinary iFABP ulcerative colitis: 38 pg/mg [29, 81] vs Controls: 53 pg/mg [27, 109], p = 0.605).ConclusionsPlasma, but not urinary iFABP is a candidate biomarker with better fidelity in monitoring compliance during GFD than TGA. The role of plasma iFABP in Crohn’s disease is promising but warrants further investigation.Trial registration: Clinical Trials.gov, NCT02341248. Registered on 19/01/2015.

Biochemical abnormalities among patients referred for celiac disease antibody blood testing in a primary health care setting

To investigate possible biochemical abnormalities associated with celiac disease (CD) antibody positivity in a primary health care setting and thereby identify predictors that could potentially reduce diagnostic delay and underdiagnosis of CD. This observational cohort study included measurements of CD antibodies in the Copenhagen Primary Care Laboratory (CopLab) database from 2000 to 2015; CD antibody positivity was defined as tissue transglutaminase antibody IgA or IgG ≥ 7 kU/L and/or deamidated gliadin peptide antibody IgG ≥ 10 kU/L. Individuals with a prior diagnosis of CD were excluded. We examined differences between individuals with positive and negative CD antibody tests regarding the results of biochemical tests performed six months before and one month after the date of the CD antibody test. We identified 76,265 measurements of CD antibodies during 2000–2015, and 57,061 individuals met the inclusion criteria (706 antibody-positive and 56,355 antibody-negative). We found lower ferritin, hemoglobin, cobalamin and folic acid levels and higher levels of transferrin, ALAT (alanine transaminase), and alkaline phosphate among individuals with a positive CD antibody test. Furthermore, we illustrated more measurements below the sex-specific reference intervals for hemoglobin, mean corpuscular volume (MCV), mean corpuscular hemoglobin concentration (MCHC), ferritin, cobalamin and folic acid among individuals with a positive CD antibody test. This study identified several biochemical abnormalities associated with CD antibody positivity among individuals referred to CD antibody testing. The pattern of abnormalities suggested that micronutrient deficiencies were prevalent among CD antibody-positive individuals, confirming malabsorption as a sign of CD. These findings illustrate the possibility of reducing diagnostic delay and underdiagnosis of CD.

Evaluation of Serum Levels of Copper and Zinc in Patients with Celiac Disease Seropositivity: Findings from the National Health and Nutrition Examination Survey.

Celiac disease is a multisystem immune based disorder, caused by an immune-mediated reaction to ingested gluten with increasing prevalence in the USA. Celiac disease can cause a wide variety of symptoms, including gastrointestinal symptoms (diarrhea, abdominal distention, or abdominal pain), which may affect absorption of many nutritional components. All patients with celiac disease should remain on a strict and lifelong gluten-free diet, which are often low in certain trace elements such as zinc. On the other hand, zinc and copper as the essential trace elements have been hypothesized to help maintain optimum function of the immune system. Then, this study aims to examine the association between celiac disease seropositivity and serum zinc and copper levels. A nationally representative sample from National Health and Nutrition Examination Survey (2011-2014) was analyzed. Celiac disease seropositivity was determined using the tissue transglutaminase IgA antibody test (IgA-TTG). Multivariable linear regression models were performed with celiac disease seropositivity as a predictor and serum zinc and copper levels as outcome. The present study included 4732 participants (1398 children aged 6-19years and 3334 adults aged ≥ 20years). The weighted prevalence of celiac disease seropositivity was higher (11.6/1000) among children aged 6-19years compared to that (6.3/1000) among adults aged ≥ 20years. In the stratified analysis by age, the multivariable linear regression analysis revealed that among children aged 6-19years, celiac disease seropositivity was associated with 5.32 (95% CI, - 9.71 to - 0.92) μg/dL lower serum zinc level, but not associated with serum copper level. However, the association between celiac disease seropositivity and serum zinc level was not statistically significant among adults aged 20years or older. Future prospective studies are warranted to confirm these findings.