Welcome to the Autoimmunity 2021 Congress Calendar
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NEO-EPITOPE TISSUE TRANSGLUTAMINASE IS THE BEST, AND NEO-EPITOPE MICROBIAL TRANSGLUTAMINASE IS A NEW BIOMARKER FOR CELIAC DISEASE DIAGNOSIS
Abstract
Background and Aims
Tissue transglutaminase (tTG) and microbial transglutaminase (mTG) cross-link gliadins to form complexes that expose immunogenic neo-epitopes to produce tTG and mTG-neoepitope antibodies. Our aim was to test the diagnostic performance of antibodies against non-complexed and complexed forms of transglutaminases, to correlate their activities to the intestinal damage in celiac disease (CD).
Methods
296 children from Sweden and 95 children from Israel with untreated CD and 359 non-celiac disease controls were checked by in-house enzyme-linked immunosorbent assays detecting IgA or combined detection of IgA and IgG (Check) against tTG, AESKULISA® tTG New Generation (tTG-neo) and mTG-neo (RUO). We graded the intestinal pathology according to the revised Marsh criteria.
Results
Using cut-offs estimated from Receiver-Operating Characteristic [DPK1] (ROC) curves, the highest area under the curve (AUC) of TG assays was 0.963/0.99 for tTG-neo Check, followed by tTG-IgA, (0.959). mTG-neo check performances were lower, whereas the tTG-neo Check was the best to reflect the intestinal abnormalities in CD (r=0.795, p<0.0001).
| Sweden | Israel | |||||
| Antibody | AUC | Sensitivity% | Specificity% | AUC | Sensitivity% | Specificity% |
| tTG-neo check | 0.963 | 90.9 | 90.4 | 0.99 | 97.98 | 100 |
| mTG-neo check | 0.903 | 75.3 | 88.8 | 0.89 | 89.9 | 87.88 |
| tTG IgA | 0.959 | 91.9 | 91.5 |
Conclusions
Based on the AUC comparison, the tTG-neo Check is the best biomarker for CD diagnosis followed by the tTG-IgA. mTG-neo Check is a new marker for CD diagnosis.
ANTI TRANSGLUTAMINASE (TTG) ANTIBODIES COULD PREDICT THE DEVELOPMENT OF CELIAC DISEASE 5 YEARS BEFORE THE DIAGNOSIS
Abstract
Background and Aims
Celiac disease (CD) is an autoimmune disease characterized by duodenal damages after gluten exposure in genetically predisposed subjects. Guidelines suggest to perform anti-transglutaminase (tTG) and anti-endomysium (EMA) for CD diagnosis. Many clinical sign and symptoms, not only gastrointestinal, are associated to CD and gluten free diet is the only available therapy. The aim of this study is to evaluate the predictive value for CD development of tTG on a chemiluminescence platform (BioFlash®, Inova).
Methods
10614 patients were tested for tTG between June 2012 and December 2013 at the clinical chemistry laboratory of Papa Giovanni Hospital (Bergamo, Italy). 515 subjects were tTG positive and we follow them up for 5 years.
Results
203/515 (39.4%) patients were excluded: 190 patients were already CD diagnosed and 13 were lost at follow up. 270/312 (86.5%) patients were diagnosed after the first tTG test or within 5 years of follow up, 42/312 (13.5%) subjects do not receive a confirmed CD diagnosis (CD was excluded for 22 subjects, 20 patients were classified as potential CD). The median tTG values between the two groups were statistically different (342.7 CU vs 35.23 CU; p<0.0001). ROC analysis showed a 95.4% probability to receive a CD diagnosis within 5 years for tTG values over 68.8 CU, it increases to 99.4% for tTG values over 170.5 CU.
Conclusions
A tTG result above 170.5 CU could predict with a very high probability the development of CD within 5 years independently from the pre-test probability.
LUPUS ANTICOAGULANT REMISSION AFTER GLUTEN-FREE DIET IN A COELIAC PREGNANT WOMAN
Abstract
Background and Aims
Coeliac disease is an immune-mediated small bowel disorder. The only treatment for coeliac disease is strict and life-long adherence to a gluten-free diet. The association between coeliac disease and autoimmune conditions, reproductive abnormalities and obstetrical complications is well reported in the literature. We report an intriguing case of successful pregnancy and lupus anticoagulant remission after gluten-free diet in a woman affected by coeliac disease and antiphospholipid syndrome.
Methods
We observed a case of a 37-year-old woman with Antiphospholipid Syndrome (APS) diagnosed after a fetal loss at the 17th week of pregnancy with positive lupus anticoagulant (LA), confirmed after 12 weeks. The coeliac disease tests also resulted positive, and the diagnosis of coeliac disease was confirmed by duodenal biopsy, so the patient started a gluten-free dietary regimen. After eight months of strict gluten-free diet, the patient was again pregnant. A standard therapy with low dose aspirin and enoxaparin sodium 4000 IU/day was started.
Results
At the beginning of the pregnancy, both LA test and serological markers for coeliac disease were repeatedly negative. At 40 weeks of gestation, a healthy baby weighing 2730 g (12th percentile) was delivered and discharged on the second day of life in good condition.
Conclusions
Gluten-free diet, by abolishing the gluten trigger, could positively influence the patient’s immunological status. In fact, both the negative coeliac disease markers and the negative LA results might reflect the beneficial effect of a gluten-free regimen also on the pregnancy outcome.
OLMESARTAN ENTEROPATHY DRESSED UP AS CELIAC DISEASE: A CASE REPORT
Abstract
Background and Aims
Olmesartan is an antihypertensive drug belonging to the angiotensin II receptor blocker class, widely used in clinical practice. In rare cases, olmesartan is responsable of a severe enteropathy, defined “sprue-like enteropathy” because its similarity with celiac disease (CD) and other enteropathy with malabsorption. We described four cases of olmesartan-related enteropathy, observed in the last months of 2019 in the “Adult Celiac Disease Surgery” of Papa Giovanni XXIII Hospital (Bergamo, Italy).
Methods
1) 68yo man, admitted to the medicine unit for weight loss (-20kg) and severe malabsorption; duodenal biopsy showed a partial villous atrophy with inflammatory infiltrate of CD3 (50/100 enterocytes) 2) 62y man, with progressively increased abdominal discomfort with watery diarrhea and moderate weight loss, duodenal biopsy with Marsh 2 and increased CD3 3) 65y female, with chronic diarrhea, moderate weight loss, multiple vitamin deficiencies and sideropenic anemia, duodenal biopsy with Marsh 2 and increased CD3 and 3) 71y man, with chronic diarrhea, sometimes with fecal incontinence of watery feces and duodenal biopsy with Marsh 1 and incresed CD3 (45/100 enterocytes)
Results
All patients was HLA DQ2/DQ8 positive; colonscopy and screening for celiac disease (anti transglutaminase, AGA and EMA) were repeatedly negative; all the other causes of enteropathy were excluded. In all the cases, the suspension of olmesartan resolved completely the symptomatology.
Conclusions
Olmesartan therapy is an uncommon cause of “sprue like enteropathy” and can give problems of differential diagnosis with CD; so, the patient's medical history is essential to avoid unnecessary investigations and reach a correct diagnosis.
IDS-ISYS MULTI-DISCIPLINE AUTOMATED SYSTEM IS A SIMPLE AND RELIABLE TOOL FOR CELIAC DISEASE DIAGNOSIS
Abstract
Background and Aims
Background and aims: The IDS-iSYS multi-discipline system is a compact fully automated instrument based on chemiluminescence technology. It is designed for unitary tests with ready-to-use reagent cartridges issued from a panel in the field of endocrinology, infectious diseases and autoimmunity. Detection of anti-tissue transglutaminase IgA (AtTG) is recognized as the best immunological serum test for celiac disease (CD) diagnosis. Our aim was to compare IDS-iSYS system and automated ELISA kit for routine detection of serum AtTG.
Methods
Methods: Serum samples from 175 patients (including 59 CD and 8 total IgA deficiencies) yet routinely evaluated for AtTG levels with the ELISA kit provided by Eurospital (Eu-tTG IgA, ref 9105, performed on a BEP III System (Siemens Healthcare Diagnostics)) and for anti-endomysium antibodies (monkey oesophagus slides from Medica) were analyzed by the IDS-iSYS system (IDS t-TG IgA, ref IS-AI1303). The repeatability and the reproducibility of the IDS test were also studied.
Results
Results: AtTG levels obtained from the two methods were similar for 171 out of 175 samples (97.7 %). Among the 4 discrepancies, clinical chart analysis was in favour of IDS-iSYS for two patients. It is worthy to note that all IgA deficiencies were detected by the IDS-iSYS. The repeatability of IDS AtTG test was very good and its reproducibility was good.
Conclusions
Conclusions: We show here that IDS-iSYS multi-discipline automated system is a simple and reliable tool for celiac disease diagnosis. Its capacity to detect IgA deficiency during the AtTG run is of interest for a good interpretation of the test.
CLINICAL STUDY OF APTIVA CELIAC DISEASE IGA AND IGG REAGENTS ON PATIENTS WITH BIOPSY RESULTS
Abstract
Background and Aims
Antibodies to tissue transglutaminase(tTG) and deamidated gliadin peptide(DGP) are important factors in diagnosis of celiac disease(CD). Increased anti-tTG IgA titers can be especially important, where a titer 10 times the upper limit of normal (>10xULN) may consider foregoing invasive intestinal biopsy in diagnosis of CD. This study aimed to compare the performance of the novel assays for tTG and DGP with the results of patients who underwent biopsy.
Methods
A total of 130 patients with suspicion of CD that underwent biopsy to confirm diagnosis were tested on Aptiva Celiac Disease IgA and IgG which utilizes a novel particle-based multi-analyte technology (PMAT, research-use-only, Inova Diagnostics, USA) and QUANTA Flash (QF) tTG and DGP IgA and IgG Reagents. Additionally, sixteen pediatric samples were tested on both Aptiva and QF
Results
59 of the 130 patients with suspicion of CD were confirmed after the biopsy. The results on the Aptiva Celiac Disease Reagents are summarized in the Table below. Of note, the one patient diagnosed with dermatitis herpetiformis was positive for QF and Aptiva tTG IgA. Of the 16 pediatric patients, all were positive for tTG IgA with results >10xULN.
Conclusions
Anti-tTG and DGP antibodies measured using the novel fully automated PMAT assay showed excellent clinical performance with high correlation to biopsy results and the QF Celiac Reagents. The tTG IgA results >10xULN in this pediatric study confirms the use of serological testing as part of the criteria (along with genetic testing and presence of anti-endomysial antibodies) for pediatric patients is an alternative to invasive biopsy.