Establishment of New Immunostatistical Equations for Diagnosis and Follow-Up of Gluten-Free Diet in Patients with Celiac Disease.

<b>Background and Objective:</b> Celiac disease (CD) is an autoimmune condition characterized by immune responses to gluten. The reported prevalence of CD has increased globally due to improved screening and diagnostic techniques, however, there is significant global variation in methods of diagnosis and follow-up. A new immunostatistical equation that determines the values of two types of antibodies using the total IgA test. <b>Materials and Methods:</b> Only 70 blood samples were taken from people who had celiac disease or were suspected of having it, with ages ranging from 5 to 40 years and they were separated into two groups. The first group contained 40 people of both sexes who had previously been diagnosed with celiac disease, while the second group included 30 individuals of both sexes, with ages ranging from 5 to 35 years, who were suspected of having celiac disease due to the appearance of some clinical symptoms. The control group also included 30 blood samples from healthy individuals of both sexes, with ages ranging from 5 to 40 years. Total IgA antibody tTG/IgA and DGP/IgA levels were estimated for all study samples. <b>Results:</b> By using a regression coefficient test the results showed the percentage of the effect of total IgA on tTG/IgA, DGP/IgA amounted to 11 and 25%, respectively, as shown by the value of the coefficient of clarifications (R²) in patients with CD. On the other hand, The percentage of the effect of total IgA on tTG/IgA and DGP/IgA amounted to 11, 14%, respectively, as shown by the value of the coefficient of clarifications (R²) in patients with suspected CD in p<u><</u>0.05. The results of the study were revealed and through the regression coefficient, four new immunostatistical equations were mathematically derived that give the value of tTG/IgA and DGP/IgA based solely on the total IgA test in the laboratory. <b>Conclusion:</b> By adopting one laboratory test which determines total IgA, the study concluded four new immunostatistical equations that will help academic researchers and attending physicians to diagnose celiac disease in addition to following up on patient's adherence to a gluten-free diet.

Celiac disease seroprevalence in subjects with dyspeptic symptoms. A study on a Mexican population.

INTRODUCTION AND AIMS: Celiac disease (CD) is an autoimmune enteropathy that develops in genetically susceptible individuals. The typical gastrointestinal manifestation is diarrhea but symptoms of dyspepsia, such as epigastric pain, nausea, or satiety, can sometimes appear. Previous studies have reported that the prevalence of CD in patients with dyspepsia can be as high as 7%. The aim of the present study was to evaluate CD seroprevalence in subjects with dyspeptic symptoms and a control group in a Mexican population. MATERIAL AND METHODS: A case-control study was conducted on blood donors that answered the PAGI-SYM questionnaire for dyspepsia and in whom IgA antibodies to tissue transglutaminase 2 (IgA anti-tTG2) and IgG antibodies to deamidated gliadin peptide (IgG anti-DGP) were determined. CD seroprevalence in subjects with dyspeptic symptoms and in asymptomatic subjects was compared. RESULTS: A total of 427 subjects (76.3% men), with a mean patient age of 34 years (range of 18-65 years) were included. Of those participants, 87 (20.3%) had symptoms of dyspepsia (group A) and 340 (79.6%) were asymptomatic (group B). Antibodies were positive in one (1.15%) of the group A subjects (1/87, 95% CI 0.2-6 %), whereas they were positive in 4 (1.18%) of the group B subjects (4/340, 95% CI 0.4-2.9%, p = 0.59). CONCLUSIONS: CD seroprevalence in the study population with dyspeptic symptoms (1%) was not different from that of the control population. Thus, CD screening in Mexican patients with dyspepsia is not justified.

Prevalence of Coeliac Disease in Omani Adults with Iron Deficiency Anaemia of Unknown Cause: Case-finding study.

Objectives: This study aimed to estimate the serological prevalence of coeliac disease in patients with iron deficiency anaemia (IDA) of unknown cause at a primary healthcare facility in Oman. Methods: This prospective case-finding study was conducted at the primary care clinics in Sultan Qaboos University Hospital, Muscat, Oman from September 2018 to June 2020. Patients aged 18 to 55 years, with a haemoglobin (Hb) level <11.5 g/dL for males and <11.0 g/dL for females and a ferritin level <30 ng/mL for males and <13 ng/mL for females, were included in the study. Blood samples were obtained for initial serological screening using serum immunoglobulin (Ig)A level; those samples with normal levels of IgA, IgA anti-tissue transglutaminase antibody (tTG) and IgA anti-deamidated gliadin peptide (DGP) were determined. Positive IgA-tTG test was confirmed using IgA-endomysial antibodies. Patients with low IgA levels were tested using IgG-tTG and IgG-DGP. Results: A total of 104 patients participated in this study. Eight patients (7.7%) were found to have a positive serological screening result for coeliac disease; of these patients, three (37.5%) had a positive IgA-tTG result. Two of those three (66.7%) had a positive IgA-endomysial antibody. The IgA-DGP result was positive in seven (6.7%) of the 104 patients. Out of those seven patients, two also had a positive IgA tTG. Conclusion: Coeliac disease is not a rare disorder. There is a need to increase awareness among healthcare professionals about coeliac disease and its non-classical manifestations such as IDA.

To DGP-IgG or not? a comparison of TTG-IgA and DGP-IgG.

BACKGROUND: We assessed the diagnostic utility of deamidated gliadin peptide immunoglobulin G (DGP-IgG) in pediatric patients without immunoglobulin A deficiency who underwent tissue transglutaminase immunoglobulin A (TTG-IgA) screening and biopsy. METHODS: Patients who had TTG-IgA performed in our laboratory had sample frozen over 1.5 y. If a patient underwent biopsy within 6 months of serology, DGP-IgG was performed on frozen sample. All testing was performed on the BioPlex 2200. Biopsies were assigned a modified Marsh-Oberhuber score. The sensitivity, specificity, and positive and negative predictive values were calculated for TTG-IgA and DGP-IgG for values ≥ 15 u/ml, 15-149 u/ml, and ≥ 150 u/ml using biopsy as gold standard. RESULTS: A total of 458 patients were included. Sensitivity and specificity for DGP-IgG ≥ 15 u/ml and Marsh ≥ 2 was 76% and 87.5% and TTG-IgA ≥ 15 was notably higher at 93.3% and 92.2%. Sensitivity and specificity of DGP-IgG were 66% and 88.9% at moderate and 29.3% and 98.4% at high increases. The positive predictive value of DGP-IgG for celiac disease in TTG-IgA negative patients was 2.8%. CONCLUSIONS: Our study suggests DGP-IgG does not add significant value in patients screened for celiac disease.

Usefulness of deamidated gliadin peptide antibodies in diagnosing coeliac disease in children younger than 3 years old.

AIM: The standard serological test to screen for coeliac disease (CD) is tissue transglutaminase (tTG) but some experts recommend including deamidated gliadin peptide (DGP) antibodies for children younger than 3 years old. This study evaluated the utility of DGP-immunoglobulin A (IgA) and DGP-immunoglobulin G (IgG) serologies when screening children younger than 3 years old for CD. METHODS: A retrospective chart review was conducted including children 3 years old and under, who had DGP and/or tTG serologies along with duodenal biopsies during their initial diagnostic evaluation. Serology results were compared to the gold-standard histopathology by χ2 to determine the significance of including DGP-IgG/IgA serologies when screening for CD in this age group. RESULTS: We identified 478 patients, 52 who were younger than 3 years old, 43 of whom met inclusion criteria. The positive predictive value (PPV) of the DGP-IgA test was 91.7% whereas, DGP-IgG was 77.8%. When DGP serology was examined in conjunction with tTG-IgA, the PPV with DGP-IgA was 90.9% and with DGP-IgG was 87.5%. CONCLUSIONS: In isolation, DGP-IgA provides a high PPV and specificity for CD in children younger than 3 years old, whereas DGP-IgG had a much lower PPV in this age group. When used alone or in conjunction with tTG-IgA, the DGP-IgA test results in a high PPV of 91.7 and 90.9%, respectively. Based on our study, we recommend obtaining both the DGP-IgA and the tTG-IgA serology when screening infants and children younger than 3 years old for coeliac disease.

Diagnostic Accuracy of IgA Anti-Transglutaminase and IgG Anti-Deamidated Gliadin for Diagnosis of Celiac Disease in Children under Two Years of Age: A Systematic Review and Meta-Analysis.

The need of adding the determination of anti-deamidated gliadin peptide (DGP) IgG to anti-transglutaminase (TTG) IgA antibodies for diagnosis of celiac disease (CD) in children <2 years of age is controversial. We performed a systematic review and meta-analysis to evaluate, by head-to-head comparison, the diagnostic accuracy of TTG IgA and DGP IgG antibodies. We searched PubMed, MEDLINE, and Embase databases up to January 2021. The diagnostic reference was intestinal biopsy. We calculated the sensitivity and specificity of these tests and the odds ratio (OR) between the tests. Fifteen articles were eligible for the systematic review and ten were eligible for the meta-analysis. Sensitivity and specificity were 0.96 (95% confidence interval (CI), 0.91-0.98) and 0.96 (95% CI, 0.85-0.99) for DGP IgG and 0.93 (95% CI, 0.88-0.97) and 0.98 (95% CI, 0.96-0.99) for TTG IgA, respectively. TTG IgA specificity was significantly higher (OR 9.3 (95% CI, 2.3-37.49); p < 0.001) while the sensitivity of DGP IgG was higher without reaching statistical significance (OR: 0.6 (95% CI, 0.24-1.51); p = 0.28). Both the meta-analysis and the systematic review showed that some children with early CD are missed without the DGP IgG test. In children <2 years of age, TTG IgA is the best CD screening test; however, the addition of DGP IgG may increase the diagnostic sensitivity.

Non-invasive prediction of persistent villous atrophy in celiac disease.

BACKGROUND: Celiac disease (CD) is an immune-mediated enteropathy that is primarily treated with a gluten-free diet (GFD). Mucosal healing is the main target of the therapy. Currently, duodenal biopsy is the only way to evaluate mucosal healing, and non-invasive markers are challenging. Persistent elevation of anti-tissue transglutaminase antibodies (aTTG) is not an ideal predictor of persistent villous atrophy (VA). Data regarding prediction of atrophy using anti-deamidated gliadin peptide antibodies (aDGP) and abdominal ultrasonography are lacking. AIM: To evaluate the ability of aTTG, aDGP, small bowel ultrasonography, and clinical and laboratory parameters in predicting persistent VA determined using histology. METHODS: Patients with CD at least 1 year on a GFD and available follow-up duodenal biopsy, levels of aTTG and aDGP, and underwent small bowel ultrasonography were included in this retrospective cohort study. We evaluated the sensitivity, specificity, and positive and negative predictive values of aTTG, aDGP, small bowel ultrasonography, laboratory and clinical parameters to predict persistent VA. A receiver operating characteristic (ROC) curve analysis of antibody levels was used to calculate cut off values with the highest accuracy for atrophy prediction. RESULTS: Complete data were available for 82 patients who were followed up over a period of four years (2014-2018). Among patients included in the analysis, women (67, 81.7%) were predominant and the mean age at diagnosis was 33.8 years. Follow-up biopsy revealed persistent VA in 19 patients (23.2%). The sensitivity and specificity of aTTG using the manufacturer's diagnostic cutoff value to predict atrophy was 50% and 85.7%, respectively, while the sensitivity and specificity of aDGP (using the diagnostic cutoff value) was 77.8% and 75%, respectively. Calculation of an optimal cutoff value using ROC analysis (13.4 U/mL for aTTG IgA and 22.6 U/mL for aDGP IgA) increased the accuracy and reached 72.2% [95% confidence interval (CI): 46.5-90.3] sensitivity and 90% (95%CI: 79.5-96.2) specificity for aDGP IgA and 66.7% (95%CI: 41.0-86.7) sensitivity and 93.7% (95%CI: 84.5-98.2) specificity for aTTG IgA. The sensitivity and specificity of small bowel ultrasonography was 64.7% and 73.5%, respectively. A combination of serology with ultrasound imaging to predict persistent atrophy increased the positive predictive value and specificity to 88.9% and 98% for aTTG IgA and to 90.0% and 97.8% for aDGP IgA. Laboratory and clinical parameters had poor predictive values. CONCLUSION: The sensitivity, specificity, and negative predictive value of aTTG and aDGP for predicting persistent VA improved by calculating the best cutoff values. The combination of serology and experienced bowel ultrasound examination may achieve better accuracy for the detection of atrophy.

Deamidated gliadin peptide and tissue transglutaminase antibodies in children with coeliac disease: A correlation study.

BACKGROUND AND STUDY AIMS: Serological tests for coeliac disease (CD) are important in the clinical diagnosis and monitoring of response to a gluten free diet (GFD). The tests differ in their sensitivity, specificity, and diagnostic accuracy. In this study, tissue transglutaminase (IgA) (tTG-IgA) antibody was compared with the deamidated gliadin peptide (DGP), of both IgG (DGP-IgG) and IgA (DGP-IgA) types, in patients with CD. PATIENTS AND METHODS: This cross-sectional study was conducted over a period of 2 years, between 2016 and 2018, at King Abdulaziz University Hospital in children 18 years of age or younger with biopsy-proven CD. Patients' sera were tested for DGP-IgA, DGP-IgG, and tTG-IgA antibodies using enzyme-linked immunosorbent assay (ELISA). A Pearson correlation coefficient and Cohen's kappa coefficient were performed to analyse the serological tests. RESULTS: The study included 26 patients with CD, with a median age of 15 years (range, 5-18 years). Seventeen patients (65.4%) were males. The median disease duration was 5 years (range, 3-14 years). Fifteen patients (57.7%) reported good adherence to a GFD. The patients' serological tests showed a mean ± SD tTG-IgA titer of 149.8 ± 75 u/ml, a mean DGP-IgG titer of 62.5 ± 36.5, and a mean DGP-IgA of 32 ± 23.3 µ/ml. We found a significant correlation between tTG-IgA and DGP-IgG (r = 0.69, P < 0.001), tTG-IgA and DGP-IgA (r = 0.67, P < 0.001), and DGP-IgG and DGP-IgA (r = 0.83, P < 0.001). Cohen's kappa coefficient (k) showed substantial agreement between tTG-IgA and DGP-IgG (k = 0.71, P < 0.001) and DGP-IgG and DGP-IgA (k = 0.69, P < 0.001), but moderate agreement between tTG-IgA and DGP-IgA (k = 0.45, P = 0.006). CONCLUSION: We found a good correlation between tTG-IgA and DGP-IgG and tTG-IgA and DGP-IgA, and substantial agreement between tTG-IgA and DGP-IgG, but moderate agreement between tTG-IgA and DGP-IgA. These results indicate that DGP-IgG was comparable to tTG-IgA and may be useful as an alternative to tTG-IgA in the diagnosis and follow-up of patients with CD.

Deamidated gliadin peptide in pediatric patients with moderately increased tissue transglutaminase; does it help?

BACKGROUND: Deamidated gliadin peptide (DGP) is a relatively new serologic assay used in diagnosis and monitoring of celiac disease. DGP IgG is recommended by some in pediatric patients <2 y. Use in other pediatric populations is not well established. The utility of the DGP screen (IgG + IgA) in patients with moderate increase of tissue transglutaminase (TTG) IgA has not been studied. METHODS: Cases between January 2015 and October 2017 in which a patient had TTG IgA greater >19 and <100, DGP screen, and biopsy were collected. Indication for biopsy and diabetes diagnosis were recorded. Of 495 patients screened, 31 met criteria. RESULTS: The sensitivity and specificity of DGP screen were calculated, and were 87.4% and 56%, respectively; though lower in patients with diabetes. CONCLUSIONS: The study suggests in patients with moderately increased TTG-IgA, DGP screen lacks specificity and does not provide additional information about whether or not to biopsy.

Prevalence of celiac disease serological markers in a cohort of Italian rheumatological patients.

AIM: To assess the prevalence of celiac disease (CD) serological markers in a cohort of patients referred to an Italian rheumatological outpatient clinic. BACKGROUND: Current guidelines do not suggest CD screening in patients with rheumatological diseases and these subjects are not considered to be at high risk for CD. METHODS: A total of 230 sera of rheumatological patients referred to the Division of Internal Medicine at the Department of Medical and Surgical Sciences between January 2005 and December 2013 were screened for CD by testing IgA antitransglutaminase (TTG IgA), IgG deamidated gliadin peptides (DGP IgG) and IgA antiendomysium (EMA) antibodies. Of the 230 patients tested, 67 had a diagnosis of rheumatoid arthritis (RA), 52 Sjögren's syndrome (SjS), 42 systemic sclerosis (SCL), 35 systemic lupus erythematosus (SLE), 15 mixed connective tissue disease, 11 polymyositis and 10 dermatomyositis. RESULTS: TTG IgA antibodies were identified in 7/230 cases (3%), 3 in SjS (3/42 - 5.8%), 2 in SCL (2/42 - 4.8%), 1 in RA (1/67 - 1.5%) and 1 in SLE sera (1/35 - 2.8%). All the seven sera were also positive for DGP IgG and EMA IgA. DGP IgG were the most frequent antibody detected, being found in 16 (7%) sera. CONCLUSION: This study identified a high prevalence of CD antibodies in adult patients referred to a rheumatology outpatient clinic. These results highlight the importance of CD screening in subjects presenting with rheumatological features.