Tissue Transglutaminase Antibodies Research Articles

THU439 Baby's Coming, Break A Leg! A Case Of Transient Osteoporosis Of The Hip

Abstract Disclosure: A. Khan: None. A. Syeda: None. H.B. Aftab: None. Introduction: Pregnancy-associated osteoporosis (PAO) is a rare condition presenting as fragility fractures usually in the latter part of pregnancy or immediate postpartum period. Vertebral fractures are more commonly reported but femoral fractures have also been described in the literature as a distinct entity: transient osteoporosis of the hip (TOH). We present a case of bilateral (B/L) femoral fractures in a woman during pregnancy and in the postpartum period. Case: A 31-year-old, gravida 1 female developed left leg pain at 26 weeks of gestation. The pain radiated from her left lower back to her left knee. It was severe in intensity resulting in her walking with crutches. Subsequent MRI of the left hip showed subchondral insufficiency fracture of the femoral head with prominent bone marrow edema extending from the head into the femoral neck. She was managed conservatively with non-weight bearing status and oral analgesics. She had an uncomplicated vaginal delivery at 39 weeks of gestation. During the first postpartum week she developed right hip pain. MRI of right hip revealed nondisplaced right femoral head subchondral insufficiency fracture with associated effusion and synovitis. She recovered within the next 3 months with resolution of her pain with conservative management. Other than limited calcium intake in childhood, there were no other identifiable risk factors for osteoporosis. Bone density scan revealed normal Z-scores at the lumbar spine and non-dominant wrist. The hips were not evaluated. Workup for secondary causes of osteoporosis was unremarkable including normal serum calcium, PTH, phosphorus, magnesium, SPEP, tissue transglutaminase antibodies, estradiol, LH, FSH, prolactin levels. However, 24-hour urine calcium level was low at 11 (35-250) mg/24hr. Elevated levels of bone specific alkaline phosphatase and urine N-telopeptide (NTX) were noted at 19.9 (5.3-19.5) mcg/L and 110 (4-64) nM BCE/mM creatinine, respectively. Patient was continued on vitamin D and calcium supplements. She breastfed for the initial 2 months but was advised to stop. At her most recent follow up visit 4 months postpartum patient was doing well. Discussion: TOH is a rare entity, and presentation as B/L femoral fractures is exceedingly rare. During pregnancy and lactation, the skeletal system undergoes bone loss to compensate for the calcium demand of the fetal skeletal system. In TOH, venous stasis from the gravid uterus resulting in bone marrow edema is the proposed mechanism in addition to pregnancy associated bone loss. In our patient, a low 24-hr urine calcium could suggest low calcium intake which could have contributed to the fracture as well. While recurrence of PAO has been described, no recurrence of TOH has been reported in subsequent pregnancies. Our case highlights the importance of keeping this rare entity on the differential in pregnant women presenting with back or hip pain. Presentation: Thursday, June 15, 2023

Serological Screening for Celiac Disease and Gastrointestinal Absorption Disorders in Patients with Autoimmune Endocrine Diseases.

Celiac disease (CD) accompanying autoimmune endocrine diseases (AED) is generally asymptomatic. This study aimed to evaluate the frequency of clinically overt or silent CD in patients diagnosed with autoimmune endocrinopathy and the clinical effects of silent CD in these endocrinopathies. The study included 166 patients with known or newly diagnosed mono-/polyglandular AED and 90 age- and gender-matched healthy controls. The patients were classified into four groups: type 1 diabetes mellitus (DM) (n=44), Hashimoto's thyroiditis (HT) (n=68), Addison's disease (AD) (n=17), and autoimmune polyglandular syndrome (APS) (n=37). All subjects were serologically screened for tissue transglutaminase antibody (tTG) IgA and IgG. In addition, to evaluate the possible systemic consequences of CD, serum parathormone (PTH), 25-hydroxicholecalsiferol (25-OH-Vit D), vitamin B12, folic acid, iron, iron-binding capacity (IBC), and ferritin levels were measured. In the total series, 193 (75.4%) individuals were females, and 63 (24.6%) were males. TTG IgA antibody positivity was found in 23 among 166 patients, while no positivity was encountered in the healthy control group. The highest rates of positive tTg IgA frequency were detected in AD, with 29.4% (5/17). Serum 25-OH-Vit D, vitamin B12, folic acid, iron, and ferritin levels were significantly lower in AEDs compared to controls (p<0.001), and the lowest these parameters were detected in patients with AD. The serologic CD prevalence is higher in autoimmune mono-/and polyglandular endocrine diseases than in the control group. The data support recommends regular screening for CD in all patients with AEDs.

Prevalence of tissue transglutaminase antibodies and IgA deficiency are not increased in juvenile idiopathic arthritis: a case-control study

BackgroundThe prevalence of Celiac Disease (CD) in Juvenile Idiopathic Arthritis (JIA) has been reported to be 0.1–7% in various small studies. As a result of the limited number of research and their inconclusive results there are no clear recommendations for routine CD screening in asymptomatic patients with JIA. Our aim is to estimate the prevalence of IgA deficiency and tissue transglutaminase (tTG) IgA in a cohort of JIA followed in two large academic medical centers.MethodsSerum was collected and stored from all subjects and analyzed in a reference laboratory for total IgA (Quantitative Nephelometry) and tTG IgA antibody levels (Semi-Quantitative Enzyme-Linked Immunosorbent Assay). Fisher’s exact tests were performed for statistical significance. Risk estimates (odds ratios) with 95% confidence intervals were calculated.Results808 JIA cases and 140 controls were analyzed. Majority were non-Hispanic whites (72% vs. 68% p = 0.309). A total of 1.2% of cases were IgA deficient compared to none of the controls (p = 0.373). After excluding IgA deficient subjects, 2% of cases had tTG IgA ≥ 4u/mL compared to 3.6% of controls (p = 0.216) (OR = 0.5; 95% C.I = 0.1–1.4); and 0.8% of cases had tTG IgA > 10u/mL compared to 1.4% of controls (p = 0.627) (OR = 0.5; 95%C.I = 0.1–2.9).ConclusionsUsing the largest JIA cohort to date to investigate prevalence of celiac antibodies, the prevalence of positive tTG IgA was 0.8% and of IgA deficiency was 1.2%. The results did not demonstrate a higher prevalence of abnormal tTG IgA in JIA. The study did not support the routine screening of asymptomatic JIA patients for CD.

Unique presentation of Mauriac syndrome with associated celiac disease in an adolescent with type 1 diabetes mellitus: A case report

We report an adolescent girl with Mauriac syndrome diagnosed in merely 3 years of diagnosis of type 1 diabetes mellitus with poor glycemic control and associated celiac disease. A 11-year-old girl with poor metabolic control characterized by recurrent hypoglycemia and hyperglycemia presented with Mauriac syndrome comprising stunting, hepatosplenomegaly, and elevated serum transaminases without cushingoid features, within 3 years of diagnosis of type 1 diabetes mellitus. Serum tissue transglutaminase antibodies were elevated. The girl also had coexisting celiac disease. She improved with adequate glycemic control along with a gluten-free diet, iron, and other supplements with regression in the size of the liver and reduction of liver enzymes. Mauriac syndrome should be considered in type 1 diabetic patients with poor metabolic control and hepatomegaly irrespective of the duration of diabetes mellitus. Recurrent hypoglycemia and the presence of Mauriac syndrome are signs of associated autoimmune disorders.

Lack of Follow-Up for Celiac Disease During Childhood Not Associated With Poor Health Outcomes: A Regional Swedish Cohort Study.

The objective of the study is to examine the association between the lack of follow-up for celiac disease (CD) during childhood and dietary adherence, disease remission, and health-related quality of life (HRQoL). We invited 243 randomly selected children diagnosed with CD in 2013-2018 in Gothenburg, Sweden, and 162 consented to participate (67%). We retrieved information on clinical follow-up and current wellbeing using medical and laboratory records data, as well as validated questionnaires on symptoms of CD, dietary adherence, and HRQoL. We analyzed tissue-transglutaminase antibodies (tTGA) as a measure of disease remission. We defined lack of follow-up as no CD-related physician/dietician-led visit or measurement of tTGA over the past 24 months of study enrollment. The mean age at study enrolment was 12.7 (range 7.8-18.2) years. Out of 162 children with an average disease duration of 5.3 (range 2.3-8.8) years, 23 (14%) lacked follow-up. tTGA had normalized in 94% [95% confidence interval (CI) = 71%-100%] of children without follow-up versus 91% (95% CI: 85%-95%) of children with continued follow-up. Of children without follow-up, 65% (95% CI: 38%-86%) reported a dietary adherence score indicating very good adherence, versus 72% (95% CI: 63%-80%) of those with continued follow-up. Also, lack of follow-up was not significantly associated with growth, symptom scores, or HRQoL. In this regional cohort study of mostly older children and adolescents, lack of follow-up for CD was not significantly linked to dietary adherence, disease remission, or HRQoL. How these results hold in larger, unselected samples with longer follow-up, including transition to adult care, warrants further study.

Evaluation of Serum Ghrelin and Leptin Levels in Patients with Celiac Disease, Type1Diabetes Mellitus and Rheumatoid Arthritis

Ghrelin and leptin are two hormones that possess multiple functions, including appetite regulation, maintenance of the tissue homeostasis and regulation of proinflammatory cytokines. A few studies on serum ghrelin and leptin levels in autoimmune diseases have exhibited conflicting results. Therefore, the present study aimed to investigate the relationship between the two energy balance hormones and autoimmune diseases. Serum ghrelin and leptin levels were assessed in 94 adult patients, 61 females and 33 males, with various autoimmune diseases (celiac disease, type 1 diabetes mellitus and rheumatoid arthritis) as well as in 35 healthy people as controls, using commercially available ELISA kits. Statistically important distinctions (P &lt; 0.05) were found between the patients and controls with regard to serum ghrelin and leptin levels. Moreover, females had higher mean serum ghrelin and leptin levels than males. On the other hand, serum ghrelin level was positively correlated with serum leptin levels (r = 0.399, P &lt; 0.05) in the RA group. Whereas no significant correlation (P &gt; 0.05) was found between serum ghrelin and leptin levels in both CD and T1DM groups. As well as the correlation of the diseases biomarkers (tissue transglutaminase antibodies, anti-tTG; glutamic acid decarboxylase antibodies, anti-GAD; and cyclic citrullinated peptide antibodies, anti-CCP) with ghrelin/leptin levels revealed that anti-CCP was the only marker that significantly (P &lt; 0.05) associated with ghrelin and leptin in patients with RA. The current study indicates a linkage between the immune system and metabolic hormones depending on response to different autoimmune conditions. Additional studies are required to understand whether changes in ghrelin-leptin levels influence the emergence of autoimmune diseases or vice versa.

#3121 THE EFFECTIVENESS OF A GLUTEN-FREE DIET IN PATIENTS WITH IGA NEPHROPATHY

Abstract Background and Aims Modern data from the world literature confirm the association of IgA nephropathy (IgAN) and celiac disease. The inclusion of a gluten-free diet (GFD) in the diet has a beneficial effect not only on gastrointestinal symptoms, but also reduces the clinical and laboratory activity of IgAN. The aim of this study was to evaluate the effect of a gluten-free diet on the course of IgAN using general clinical and immunological tests 6 months after the start of its use. Method 65 patients with morphologically confirmed IgAN were included in the study. To detect a violation of gluten metabolism, screening determination of the level of IgA antibodies to tissue transglutaminase (Anti-TTG IgA) and IgA antibodies to deamidated gliadin peptides (Anti-DPG IgA) was performed. According to the results of the screening examination, a group of patients with the level of antibodies exceeding the reference values were formed (group 1, n = 13) and a group of patients in whose blood did not exceed the reference values, or were absent at all (group 2, n = 52). Patients of both groups were recommended GFD for a period of at least 6 months. The effectiveness of GFD was evaluated by the following indicators: protein in urine (g/l); red blood cells in urine (RBCs) (hpf); daily proteinuria (g/day); blood creatinine (mmol/l), GFR calculated by the formula CKD-EPI (ml/min /1.73 m2) at the beginning of the study and 6 months after the inclusion of dietary recommendations. Statistical analysis of the data obtained was carried out using the statistical program SPSS Statistics 26.0 (IBM, USA). When comparing quantitative indicators, the distribution of which differed from normal in two related groups, the Wilcoxon criterion was used. The null statistical hypothesis about the absence of differences and connections was rejected at p&amp;lt;0.05. Results among the examined patients there were 61 men (93.8%), 4 women (6.2%). The average age of men was 39.0±8.2 years, women - 34.7±9.7 years. The duration of the underlying disease at the time of inclusion in the study was 55.98 [40.67-71.28] months. 57 people (85.1%) received ACE inhibitors/sartans in therapeutic doses as the main therapy, 8 people (11.9%) did not receive drug therapy. It was possible to evaluate the effectiveness of GFD in patients from group 1 in 9 people. During the follow-up period, 2 patients from group 1 showed progression of the disease to the End-Stage Renal Disease (GFR according to CKD-EPI &amp;lt;15 ml/min/1.73 m2), which required their exclusion from the study, in 2 more patients it was not possible to evaluate the effectiveness of GFD due to insufficient follow-up periods (less than 6 months.) GFD was also recommended to patients from group 2. Dietary restrictions were applied to patients with daily protein loss &amp;gt; 0.5 g/day and/or anti-TTG IgA and anti-DPG IgA levels in the range of pre-reference values, thus it was possible to evaluate the effectiveness of GFD in patients of group 2 in 21 people. According to the results of the analysis, a statistically significant decrease in daily proteinuria (p = 0.028) and microscopic hematuria (p = 0.018) was revealed. After 6 months from the start of compliance with GFD, daily proteinuria decreased in 66.7%; microscopic hematuria – in 77.8% in group 1 patients. Among group 2 patients, a statistically significant decrease in microscopic hematuria (p = 0.05) was observed in 76.2% of those included in the study. Conclusion the inclusion of GFD in the diet of patients with IgAN is justified in patients with the presence of gluten antibodies in the blood serum, as it allows to significantly reduce the severity of proteinuria, microscopic hematuria in these patients. Screening examination of patients with IgAN for gluten metabolism disorders will expand therapeutic possibilities, and GFD can become part of a nephroprotective strategy.

Endocrinological, immunological and metabolic features of patients with Fabry disease under therapy.

Fabry disease is an X-linked lysosomal disorder caused by decreased or absent alpha galactosidase enzyme. The enzyme deficiency leads to progressive accumulation of globotriaosylceramide (Gb-3) and its deacetylated form lyso-Gb3 in various tissue lysosomes that results in primarily lysosomal deterioration and subsequently mitochondrial, endothelial, and immunologic dysfunctions. The endocrinological, metabolic, immunological and HLA status of 12 patients were evaluated. A total of 11 patients (91.6 %) had immunologic and/or endocrinologic abnormalities. fT4, anti-TPO, and anti-TG levels were increased in 1, 2, and 2 patients, respectively. Three patients had elevated proinflammatory cytokines. ANA profile, p-ANCA and c-ANCA were positive in 1, 1, and 2 patients, respectively. Tissue transglutaminase antibody was negative in all patients however P5 was diagnosed with Celiac disease at the age of 12 and on gluten free diet. All patients had distinct types of HLA apart from 2 patients with anti-TG and anti-TPO positive and there was no relationship between the HLA types and the autoimmunity biomarkers. FD may have impact on endocrinologic and immunologic abnormalities even in the patients under ERT, therefore prevalence of these abnormalities may be higher in ERT naïve patients. However, apparently, they are less likely to cause clinical symptoms. Certain HLA alleles may contribute to the direct impact of immunological pathogenesis in FD by developing abnormal autoimmune biomarkers. To the best of our knowledge, this is the first study investigating HLA status of FD patients; therefore further studies are needed to elucidate the underlying mechanism of action.

The risk for celiac disease after Covid-19 infection

BackgroundCeliac disease (CD) is an autoimmune disease leading to gastrointestinal symptoms and mineral deficiencies. The pathogenetic mechanisms, besides the clear HLA association, are elusive. Among environmental factors infections have been proposed. Covid-19 infection results in a systemic inflammatory response that often also involves the gastrointestinal tract. The aim of the present study was to investigate whether Covid-19 infection could increase the risk for CD.Patients and methodsAll patients, both children and adults, in the county Skåne (1.4 million citizens) in southern Sweden with newly diagnosed biopsy- or serology-verified CD or a positive tissue transglutaminase antibody test (tTG-ab) during 2016–2021 were identified from registries at the Departments of Pathology and Immunology, respectively. Patients with a positive Covid-19 PCR or antigen test in 2020 and 2021 were identified from the Public Health Agency of Sweden.ResultsDuring the Covid-19 pandemic (March 2020 – December 2021), there were 201 050 cases of Covid-19 and 568 patients with biopsy- or serology-verified CD or a first-time positive tTG-ab tests, of which 35 patients had been infected with Covid-19 before CD. The incidence of verified CD and tTG-ab positivity was lower in comparison to before the pandemic (May 2018 – February 2020; 22.5 vs. 25.5 cases per 100 000 person-years, respectively, incidence rate difference (IRD) -3.0, 95% CI -5.7 – -0.3, p = 0.028). The incidence of verified CD and tTG-ab positivity in patients with and without prior Covid-19 infection was 21.1 and 22.4 cases per 100 000 person-years, respectively (IRD − 1.3, 95% CI -8.5–5.9, p = 0.75).ConclusionsOur results indicate that Covid-19 is not a risk factor for CD development. While gastrointestinal infections seem to be an important part of the CD pathogenesis, respiratory infections probably are of less relevance.

Prevalence of Organ-Specific Autoimmunity in Patients With Type 1 Diabetes Mellitus.

Type 1 diabetes mellitus (T1DM) is associated with other autoimmune disorders that are characterized by presence of organ-specific autoantibodies. The present study was undertaken to assess theprevalence of organ-specific autoantibodies amongnewly diagnosed T1DM subjects of Indiaand to studyits relationshipwith glutamic acid decarboxylase antibody (GADA). We also compared the clinical and biochemical parameters in GADA-positive and -negative T1DM subjects. In a hospital-based cross-sectional study, we studied 61 patients with newly diagnosed T1DM ≤ 30 years of age. T1DM was diagnosed on the basis of acute onset of osmotic symptoms with or without ketoacidosis, severe hyperglycaemia [blood glucose > 13.9 mmol/l (>250 mg/dl)] and insulin requirement from the onset of diabetes. Subjects were screened for autoimmune thyroid disease (thyroid peroxidase antibody [TPOAb]), celiac disease (tissue transglutaminase antibody [tTGAb]), and gastric autoimmunity (parietal cell antibody [PCA]). Of the 61 subjects, more than one-third (38%) had at least one positive organ-specific autoantibody. In particular, 13 (21.3%) were found to be positive for TPOAb, nine (14.8%) were positive for tTGAb and 11 (18%) were positive for PCA. GADA was positive in 15 (25%) subjects.The frequency of TPOAb tended to be higher in patients who had GADA positivity compared with those with no circulating GADA (40% vs.15.2%;p=0.07). Subjects positive for GADA were also more likely to be PCA positive compared with those who were GADA negative (40 vs.10.9%, p=0.02). There were no differences in frequency of diabetic ketoacidosis, body mass index, hemoglobin A1C (HbA1c), insulin requirement or fasting C-peptidein GADA-positive and -negative patients. We support the recommendation for regular screening of organ-specific autoantibodies, in particular TPOAb, tTGAb and PCA in all patients with T1DM. Detection of these autoantibodies at onset may prevent complications associated with delayed diagnosis of these disorders. We also conclude that there is higher frequency of TPOAb and PCA in GADA-positiveT1DM patients as compared to negative ones. However, patients with positive GADA had similar clinical and biochemical parameters compared to GADA-negative subjects. Lastly, low GADA positivity in our study cohort as compared to Western populations suggests the heterogenous nature of T1DM in the Indian population.

Evaluation of a Single Determination of Gluten Immunogenic Peptides in Urine from Unaware Celiac Patients to Monitor Gluten-Free Diet Adherence.

Usually, adherence to the gluten-free diet (GFD) in celiac patients is indirectly assessed through serological analysis, questionnaires, or invasive methods such as intestinal biopsy. The detection of gluten immunogenic peptides in urine (urinary gluten immunogenic peptides-uGIP) is a novel technique that directly evaluates the ingestion of gluten. The aim of this study was to evaluate the clinical efficacy of uGIP in the follow-up of celiac disease (CD). From April 2019 to February 2020, CD patients reporting complete adherence to the GFD were prospectively enrolled but were unaware of the reason for the tests. Urinary GIP, the celiac dietary adherence test (CDAT), symptomatic visual analog scales (VAS), and tissue transglutaminase antibodies (tTGA) titres were evaluated. Duodenal histology and capsule endoscopy (CE) were performed when indicated. A total of 280 patients were enrolled. Thirty-two (11.4%) had a positive uGIP test (uGIP+). uGIP+ patients did not show significant differences in demographic parameters, CDAT, or VAS scores. The tTGA+ titre was not related to the positivity of uGIP (14.4% vs. 10.9% in patients with tTGA+ and tTGA-). Regarding histology, 66.7% of the GIP+ patients had atrophy compared to 32.7% of the GIP patients (p-value 0.01). However, the presence of atrophy did not correlate with tTGA. Mucosal atrophy was detected in 29 (47.5%) out of 61 patients by CE. With this method, no noticeable dependence on uGIP results (24 GIP- vs. 5 GIP+) was observed. The single uGIP test was positive in 11% of CD cases referring a correct GFD adherence. Furthermore, uGIP results significantly correlated with the duodenal biopsy, formerly considered the gold standard for assessing CD activity.

Variation in Testing for and Incidence of Celiac Autoimmunity in Canada: A Population-Based Study

The incidence of biopsy-confirmed celiac disease has increased. However, few studies have explored the incidence of celiac autoimmunity based on positive serology results. A population-based cohort study assessed testing of tissue transglutaminase antibodies (tTG-IgA) in Alberta from 2012 to 2020. After excluding prevalent cases, incident celiac autoimmunity was defined as the first positive tTG-IgA result between 2015 and 2020. Testing and incidence rates for celiac autoimmunity were calculated per 1000 and 100,000 person-years, respectively. Incidence rate ratios (IRRs) were calculated to identify differences by demographic and regional factors. Average annual percent changes (AAPCs) assessed trends over time. The testing rate of tTG-IgA was 20.2 per 1000 person-years and remained stable from 2012 to 2020 (AAPC, 1.2%; 95% confidence interval [CI], -0.5 to 2.9). Testing was higher in female patients (IRR, 1.66; 95% CI, 1.65-1.66), those living in metropolitan areas (IRR, 1.39; 95% CI, 1.38-1.40), and in areas of lower socioeconomic deprivation (lowest compared to highest IRR, 1.24; 95% CI, 1.23-1.25). Incidence of celiac autoimmunity was 33.8 per 100,000 person-years and increased from 2015 to 2020 (AAPC, 6.2%; 95% CI, 3.1-9.5). Among those with tTG-IgA results ≥10 times the upper limit of normal, the incidence was 12.9 per 100,000 person-years. The incidence of celiac autoimmunity was higher in metropolitan settings (IRR, 1.28; 95% CI, 1.21-1.35) and in the least socioeconomically deprived areas compared to the highest (IRR, 1.22; 95% CI, 1.14-1.32). Incidence of celiac autoimmunity is high and increasing, despite stable testing rates. Variation in testing patterns may lead to underreporting the incidence of celiac autoimmunity in nonmetropolitan areas and more socioeconomically deprived neighborhoods.

Prevalence and clinical forms of celiac disease in siblings of children with verified disease

Introduction/Objective. Celiac disease (CD) is the result of a polygenic predisposition and gluten-containing diet. The aim of this study was to determine the prevalence and clinical forms of CD in siblings of children with verified disease. Methods. The study included 83 siblings, aged 1.5?27 (11.77 ? 6.2) years, of 64 children with CD diagnosed according to ESPGHAN criteria (1990/2012). In addition to a detailed history and clinical examination, serum levels of IgA and antibodies to tissue transglutaminase (AtTG) IgA and IgG classes were determined in all subjects. All with elevated AtTG levels underwent multiple duodenal enterobiopsy. The diagnosis of CD was confirmed by the finding of characteristic histological changes. Results. The diagnosis of CB was made in 13 of 83 subjects (15.67%). Nine of them had an asymptomatic form of the disease, while in the others the disease was clinically manifested ? in three the form was classical, in one it was accompanied by severe malnutrition (-26.80%), and in one the manifestation was nonclassical (only short stature). Except for sideropenia and hypoferritinemia in four patients, of which two with hemoglobin below the reference value, standard laboratory findings were within normal limits. Conclusion. Our research shows that the prevalence of CD in siblings of children with verified disease is 15.67%. It is mostly detected in its asymptomatic form. In accordance with this, routine application of serological screening for CD in this population group is necessary for its timely diagnosis and treatment.

Популяционное исследование распространенности целиакии среди школьников г. Москвы

Objective. Examination of schoolchildren in Moscow using a specially designed questionnaire to identify children at risk of developing celiac disease. Patients and methods. The study enrolled 3070 Moscow schoolchildren aged 7–18 years old. Serological and genetic examinations were performed in 42 children at risk for celiac disease, including determination of IgA and IgE to wheat, IgA and IgG to tissue transglutaminase, and IgA to endomysium. Molecular HLA testing for alleles that predispose to celiac disease was conducted. Endoscopic and morphological diagnostics were performed when indicated. Results. The risk group for celiac disease amounted to 10.2% of all schoolchildren surveyed. According to the results of the questionnaire, children in the risk group significantly more often had abdominal pain, excess gas, bloating, flatulence, dyspeptic complaints (diarrhea, constipation, vomiting), asthma attacks or other forms of allergies, headache, joint or body pain, fatigue and weakness, mood swings, depression, anxiety, or episodes of emotional arousal. Changes in height, weight, delayed physical or sexual development, dental enamel defects, and skin rashes were also noted. Of the 42 children in the risk group, the DQ2 heterodimer was detected in 13 (31%) children, the DQ8 heterodimer – in 2 (4.8%), and a combination of DQ2 and DQ8 heterodimers – in 1 (2.4%). Thus, characteristic HLA haplotypes were identified in 38% of the examined children. Three children had IgA antibodies to tissue transglutaminase (at &gt;10 norm) and IgA anti-endomysium antibody titers. Conclusion. The method of questioning by means of a specially designed questionnaire for school-age children allows to identify individuals at risk of developing celiac disease. According to serological, genetic, endoscopic, and morphological investigations, the incidence of celiac disease among children at risk was 7.1%. The prevalence of celiac disease among school-age children in Moscow corresponds to global trends, amounting to 0.7%. Key words: questionnaire, gluten-free diet, cereals, gluten intolerance, celiac disease, children

Anti-tissue Transglutaminase Enzyme-Linked Immunosorbent Assay for Screening of Celiac Disease in Moroccan Pediatric Patients

Celiac disease (CD) is an immune-mediated systemic disorder elicited by gluten which induces an enteropathy with atrophy of intestinal villi. No prevalence information was available for CD in Moroccan children because the diagnosis is based on multiple invasive duodenal biopsies. To simplify CD diagnosis, the objective of this work was to develop an Enzyme-linked Immunosorbent Assay (ELISA) for IgA and IgG tissue transglutaminase (tTG) antibodies detection suitable for Moroccan children. The concentration of the coated antigen and serum dilutions were optimized for the development of IgA anti- tTG and IgG anti-tTG ELISA detection in serum. The cut-off was calculated and the developed ELISAs were used for detecting IgA and IgG-tTG antibodies in 97 serum samples from 97 children aged 1 to 13 years, with variable clinical characteristics. After adjusting optimal working conditions of ELISA, the cut-offs were 0.04 and 0.156 AU for detecting anti-tTG and IgA anti-tTG IgG respectively. The use of IgG anti-tTG as CD marker (100 % of sensitivity) was better than the use of IgA anti-tTG in ELISA tests (90.3% sensitivity). In addition, the ELISA test shows a clear correlation between the IgG tTG antibodies titer and the degree of duodenal damage, estimated by the Marsh stages classification in patients with confirmed CD. Our results suggest that the assessment of the adapted IgG anti-tTG ELISA test can be used for CD in initial screening in Moroccan children after validation with a larger number of samples with CD for confirmation.

The Association of Inflammatory Bowel Disease with Coeliac Disease and Coeliac Autoimmunity in Children and Adults: A Nationwide Study from the epi-IIRN.

Given the paucity of population-based data on the association between inflammatory bowel diseases [IBD], coeliac disease [CeD], and coeliac autoimmunity [CeA] we aimed to study the associations in a nationwide study. Using health administrative data for all four health maintenance organisations in Israel, covering 98% of the population, we explored the prevalence of CeD in children and adults with IBD versus non-IBD matched controls. CeD was defined by three ICD-9 codes and CeA by positivity for tissue transglutaminase antibodies. In total, 34 375 IBD patients (56% Crohn's disease [CD] and 44% ulcerative colitis [UC]) were compared with 93 603 non-IBD controls. Among IBD patients, 319 [0.93%] had CeD versus 294 [0.31%] non-IBD controls (odds ratio [OR] = 2.97, 95% confidence interval [CI] 2.54-3.48; p <0.001). CeA was identified in 575 [1.67%] IBD patients vs 158 [0.17%] controls [OR = 10.06, 95% CI 8.43-12; p <0.001]. The prevalence of CeD was higher in paediatric-onset IBD (87/5243 [1.66%]) than adult-onset IBD (232/29 132 [0.79%]; p <0.001). CD patients had a higher prevalence of CeD (229/19 264 [1.19%]) than UC patients (90/15 111 [0.56%]; OR = 2.01, 95% CI 1.57-2.56; p <0.001). The diagnosis of CeD preceded the diagnosis of IBD in 241/319 cases [76%]. The time to treatment escalation was shorter in patients with both IBD and CeD than in patients with IBD without CeD [p = 0.017]. CeD and CeA are more prevalent in IBD patients, especially in paediatric-onset IBD and in CD. The diagnosis of CeD usually precedes that of IBD. Having CeD is associated with more intensified treatment for IBD.

Corneal Langerhans cells in children with celiac disease

Celiac disease (CeD) is a common small bowel enteropathy characterized by an altered adaptive immune system and increased mucosal antigen presenting cells. This study aims to establish if quantification of corneal Langerhans cells (LCs) using corneal confocal microscopy (CCM) could act as a surrogate marker for antigen presenting cell status and hence disease activity in children with CeD. Twenty children with stable CeD and 20 age-matched controls underwent CCM and quantification of central corneal total, mature and immature LC density. There was no difference in age (11.78 ± 1.7 vs. 12.83 ± 1.91; P = 0.077) or height (1.38 ± 0.14 vs. 1.44 ± 0.13; P = 0.125). BMI (18.81 ± 3.90 vs. 22.26 ± 5.47; P = 0.031) and 25 OHD levels (43.50 ± 13.36 vs. 59.77 ± 22.45; P = 0.014) were significantly lower in children with CeD compared to controls. The total (33.33(16.67–59.37) vs. 51.56(30.21–85.42); P = 0.343), immature (33.33(16.67–52.08) vs. 44.79(29.17–82.29); P = 0.752) and mature (1.56(0–5) vs. 1.56(1.04–8.33); P = 0.752) LC density did not differ between the CeD and control groups. However, immature (r = 0.535, P = 0.015), mature (r = 0.464, P = 0.039), and total (r = 0.548, P = 0.012) LC density correlated with age. Immature (r = 0.602, P = 0.038) and total (r = 0.637, P = 0.026) LC density also correlated with tissue transglutaminase antibody (Anti-TtG) levels assessed in 12/20 subjects with CeD. There was no difference in corneal LC density between children with CeD and controls. However, the correlation between corneal LC density and anti-TtG levels suggests a relationship with disease activity in CeD and requires further study.

Celiac Disease: a review

Celiac Disease (CD) is an immune-mediated enteropathy in response to the ingestion of gluten in genetically predisposed individuals, causing a malabsorptive syndrome. This review aims to conceptualize CD, describe its pathophysiology, highlight its epidemiology, detail associated clinical presentations, outline the diagnostic approach, and explain the treatment. To achieve this, works in English, Portuguese, and Spanish from the last five years were sought in the following databases: PubMed, LILACS, and SciELO, using the following keywords: “doença celíaca” and “celiac disease.” The search resulted in 175 articles, with 40 works chosen after screening and evaluation. The results revealed that CD affects approximately 1% of the global population, can be diagnosed at any age, but with more typical symptoms in children and atypical symptoms in adults. The pathogenesis involves the genetic factor HLA DQ2/DQ8, gluten ingestion, the formation of tissue transglutaminase antibodies, and an inflammatory reaction that damages the duodenum, impairing its absorptive function. Typical symptoms include chronic diarrhea, abdominal distension, weight loss, poor growth, and vitamin deficiencies. Atypical symptoms include dermatitis herpetiformis, refractory iron-deficiency anemia, delayed puberty, infertility, and neurological diseases. Diagnosis involves a suspected clinical picture, serologies for autoantibodies, genetic testing, and duodenal biopsy. Treatment is lifelong adherence to a gluten-free diet. Despite being well-characterized, CD remains underdiagnosed, and additional studies are needed.

Incidence of Pediatric Celiac Disease Varies by Region.

The Environmental Determinants of Diabetes in the Young study follows an HLA risk selected birth cohort for celiac disease (CD) development using a uniform protocol. Children under investigation come from 6 different regions within Europe and the United States. Our aim was to identify regional differences in CD autoimmunity and CD cumulative incidence for children born between 2004 and 2010. Children (n = 6,628) with DQ2.5 and/or DQ8.1 were enrolled prospectively from birth in Georgia, Washington, Colorado, Finland, Germany, and Sweden. Children underwent periodic study screening for tissue transglutaminase antibodies and then CD evaluation per clinical care. Population-specific estimates were calculated by weighting the study-specific cumulative incidence with the population-specific haplogenotype frequencies obtained from large stem cell registries from each site. Individual haplogenotype risks for CD autoimmunity and CD varied by region and affected the cumulative incidence within that region. The CD incidence by age 10 years was highest in Swedish children at 3%. Within the United States, the incidence by age 10 years in Colorado was 2.4%. In the model adjusted for HLA, sex, and family history, Colorado children had a 2.5-fold higher risk of CD compared to Washington. Likewise, Swedish children had a 1.4-fold and 1.8-fold higher risk of CD compared with those in Finland and Germany, respectively. There is high regional variability in cumulative incidence of CD, which suggests differential environmental, genetic, and epigenetic influences even within the United States. The overall high incidence warrants a low threshold for screening and further research on region-specific CD triggers.

S2789 A Rare Triad of Ulcerative Colitis, Large Vessel Vasculitis and Celiac Disease

Introduction: Inflammatory bowel disease (IBD) has been associated with large-vessel vasculitis (LVV), with the diagnosis of IBD preceding that of LVV by years. We present for the first time in known literature a triad of concurrent ulcerative colitis (UC), aortitis and celiac disease. Case Description/Methods: A 58 year old Hispanic man with a history of hypertension and gout presented with two weeks of intractable temporomandibular headaches, and two months of non-bloody diarrhea and weight loss. Physical exam was unremarkable. Labs showed hemoglobin 6.9 g/dL, erythrocyte sedimentation rate 120 mm/hr, C-reactive protein 281 mg/dL and IgA tissue transglutaminase antibody 23 U/mL. ANA, C3, C4, proteinase-3 and myeloperoxidase antibodies were within normal limits. Colonoscopy showed pancolitis from rectum to ascending colon. The terminal ileum was normal. Abdominal MRI found aortic wall hyperintensity from the renal arteries to common iliac bifurcation. CT angiogram showed wall thickening of the left carotid artery, aortic arch, descending thoracic and abdominal aorta, consistent with vasculitis. Patient was given stress dose steroids with improvement in headache and normalization of ESR and CRP. Temporal artery biopsy was unremarkable. Four months after hospitalization, repeat colonoscopy with duodenal biopsies for celiac disease revealed mild increase in intraepithelial lymphocytes with preserved villous architecture. He was started on a gluten free diet and adalimumab in combination with methotrexate for UC and LVV. Discussion: About 10 case reports of patients with both UC and either Takayasu (TAK) or giant cell arteritis (GCA) have been described, with UC typically diagnosed 15-45 years before the vasculitis. Vasculitis in the GI tract can mimic IBD, making colonoscopy and biopsy crucial for diagnosis. HLA haplotypes A24, B52, and DR2 are associated with both UC and aortitis and Interleukin-9, observed in temporal arteritis lesions, may be implicated in the pathogenesis of UC. Shared chromosomal variants between patients with UC and celiac disease may explain why IBD risk is up to 9-fold higher in patients with celiac disease. Our patient may have presented with isolated aortitis or an early form of GCA. Methotrexate is used to treat LVV and is combined with an anti-TNF agent to treat UC, as in our case. This is the first known report of co-occurring UC, celiac disease and aortitis; however, whether the three inflammatory conditions are mechanistically related warrants further research.