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Gluten-Free-Diet Management/Coping

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Gluten-Free-Diet Management/Coping ABSTRACT BOOK ORAL COMMUNICATIONS ORAL COMMUNICATIONS THEME : DIAGNOSIS Abstract #: ICDS00082 Title: Post-Mortem Immuno-Pathological Findings in the Cerebellum of Coeliac Disease patients with concomitant Idiopathic Neurological Disorders Presenting author: Maxine Rouvroye Co-authors: Maxine ROUVROYE (1), Annemieke ROZEMULLER (2), Paul VAN DER VALK (2), Hetty BONTKES (3), Chris MULDER (4), Anne-Marie VAN DAM (5), Gerd BOUMA (1) - (1)Amsterdam UMC, Vrije Universiteit Amsterdam, Department of Gastroenterology and Hepatology, AG&M research institute, Pays-Bas, (2)Amsterdam UMC, Vrije Universiteit Amsterdam, Department of Pathology, Pays-Bas, (3)Amsterdam UMC, Vrije Universiteit Amsterdam, Department of Clinical Chemistry, Medical Immunology Laboratory, Pays-Bas, (4)Amsterdam UMC, Department of Gastroenterology and Hepatology, AG&M research institute, Pays-Bas, (5)Amsterdam UMC, Vrije Universiteit Amsterdam, Department of Anatomy and Neurosciences, Pays-Bas ABSTRACT CONTENT Objectives In the past decades, various neurodegenerative disorders, like ataxia, have been associated with coeliac disease (CD). However, the underlying neuropathological mechanism is still unclear. We postulate that an erroneous immune-mediated response by means of CD8+ T-cells inflicting neuronal damage is at the base of the aetiology. Our aim was to profile different lymphocytes in the cerebellum and their proximity to (vanished) Purkinje cells (PC). Methods Post-mortem cerebellar tissue was collected of deceased CD patients with concomitant neurological disorders (Neuro-CD). Gender- and age-matched spinocerebellar ataxia (SCA) controls and non-neurological controls (NNC) were selected based on clinical reports and pathological findings. Paraffin-embedded sections were stained for CD3, CD8 and Calbindin. Per patient, 10 stretches of 900mu were screened for CD3+ and CD8+ T-cells in all cerebellar layers. A total of 18.000mu of Purkinje cell layer was inspected for PCs. Results Cerebellar tissue of sixteen patients was included (5 Neuro-CD, 5 SCA, 6 NNC). Groups did not differ in gender or age of death. More CD3+ and CD8+ cells were observed in the Neuro-CD group (median [IQR]); Neuro-CD 145 [80-264], SCA 12 [9- 35], NNC 21 [10-51] (p =0.010) and Neuro-CD 156 [30-253], SCA 10 [8-17], NNC 5 [3-16] (p =0.010); respectively. In Neuro- CDs, more CD8+ cells were found in the PC layer compared to SCAs and NNCs (p =0.007). Extensive loss of PCs was observed in the Neuro-CD group in comparison to the other groups (p =0.004). Conclusion In this post-mortem study we counted significantly more CD3+ and CD8+ lymphocytes and demonstrated a significant loss of Purkinje cells in the cerebella of Neuro-CD patients vs SCA and non-neurological controls. These findings strengthen our hypothesis of a T-cell-mediated response in the cerebellum of patients affected by Neuro-CD. Future research should focus on further characterisation of these CD8+ T-cells and exploring possible target epitopes. Conflicts of interests Nothing to declare. ORAL COMMUNICATIONS THEME : DIAGNOSIS Abstract #: ICDS00152 Title: Simultaneous transcriptional characterisation and clonal inference of disease-specific plasma cells in coeliac disease Presenting author: Ida Lindeman Co-authors: Ida LINDEMAN (1), Justyna POLAK (2), Linn M. EGGESBØ (1), Omri SNIR (2), Knut E. A. LUNDIN (3), Shuo-Wang QIAO (1), Ludvig M. SOLLID (1) - (1)K. G. Jebsen Centre for Coeliac Disease Research, University of Oslo and Department of Immunology, University of Oslo and Oslo University Hospital-Rikshospitalet, Norvège, (2)Department of Immunology, University of Oslo and Oslo University Hospital-Rikshospitalet, Norvège, (3)Department of Gastroenterology, Oslo University Hospital-Rikshospitalet and K. G. Jebsen Centre for Coeliac Disease Research, University of Oslo, Norvège ABSTRACT CONTENT Objectives Plasma cells (PCs) are terminally differentiated lymphocytes of the B-cell lineage secreting large amounts of antibodies. PCs are especially abundant in the lamina propria of the small intestine. Coeliac disease (CD) can be characterised by plasmacytosis in the lamina propria and the presence of high numbers of disease-specific PCs, of which most target the autoantigen transglutaminase 2 (TG2) and a smaller fraction target gluten peptides. The contribution of PCs toward the pathogenesis of CD has yet to be resolved. Methods We sorted single CD38+ TG2-specific, gliadin-specific or non-TG2/gliadin-specific PCs from untreated CD patients, CD patients on a gluten-free diet and non-CD controls. We performed single-cell RNA-sequencing of the sorted cells and reconstructed their B-cell receptors and identified clonally related cells with the computational tool BraCeR. Results A significantly higher fraction of the disease-specific compared to non-disease-specific intestinal PCs in untreated CD patients (n=10) were CD19+CD45+, a compartment of PCs that has previously been shown to be short-lived. Furthermore, we found that intestinal PCs express mRNA for molecules associated with antigen presentation and cross-talk with T cells, such as HLA class II, cytokines and cytokine receptors. Lastly, we investigated clone-specific transcriptional signatures among the disease-specific PCs. Conclusion Our findings support previous reports showing that PCs may have functions in addition to antibody secretion. These results suggest that PCs may have a more active role in immunological diseases than previously thought, through cross-talk with helper T cells. We anticipate that our findings could provide a basis for studies involving targeted therapy against PCs in CD and potentially also in other autoimmune diseases. Conflicts of interests The authors declare no conflicts of interests. ORAL COMMUNICATIONS THEME : DIAGNOSIS Abstract #: ICDS00171 Title: IgA anti-tTG co-localization for identification of Celiac Associated Liver Diseases Presenting author: Prasenjit Das Co-authors: Prasenjit DAS, Rimlee DUTTA, Asif IQBAL, Alka SINGH, Vineet AHUJA, Siddhartha DATTAGUPTA, Govind MAKHARIA - (1)All India Institute of Medical Sciences New Delhi, Inde ABSTRACT CONTENT Objectives The summary of evidence points towards direct involvement of liver in patients with celiac disease; there however is a lack of methods to demonstrate celiac specific lesion in the liver. IgA anti-tissue transglutaminase (anti-TG2) immunostaining of the intestinal biopsies has been reported to be specific for CeD. Methods 146 treatment-naive patients with CeD were investigated for liver dysfunction based on hyper-transaminasemia or evidence of chronic liver disease based on ultrasound and fibroscan. Those having liver abnormalities underwent liver biopsies, and the biopsies were examined microscopically for type of histological lesions. IgG anti-tTG and IgA co- localization were performed by both multicolor immunohistochemical and confocal microscopic techniques on paraffin embedded tissue. They were followed on a gluten-free diet, and follow-up biopsies were done in a subset. Liver biopsies from other causes of chronic hepatitis were used as controls. Results Twenty-seven patients (18.5%) had either biochemical or structural liver abnormalities, of whom 25 consented for liver biopsies. The lesions observed were chronic hepatitis (12%), autoimmune hepatitis (12%), steatohepatitis (12%), obliterative portal venopathy (8%), granuloma (4%), cirrhosis (8%) and sinusoidal dilatation (44%). While liver biopsies from all patients with CeD showed IgA/ anti-tTG colocalization either in sinusoidal lining cells or focally in hepatocyte cytoplasm; none of the controls showed similar colocalization. Overall, the IgA/ anti-tTG co-localization technique showed 100% sensitivity, 77% specificity and 85% positive predictive value for diagnosing celiac associated liver disease. Follow-up liver biopsies could be done in 5 patients; four of them showed complete resolution of histological lesions and disappearance of IgA/ anti-tTG co-localization. Conclusion Data of present study adds to body of evidence that liver lesions in patients with CeD are celiac specific and may have been caused by a similar pathogenetic mechanism as that in intestinal lesions. Conflicts of interests All authors declare no conflict of interest. ORAL COMMUNICATIONS THEME : EPIDEMIOLOGY/DIAGNOSTIC Abstract #: ICDS00221 Title: Mass Screening for celiac disease in school-age children: the CELI-SCREEN multicenter study. Presenting author: Elena Lionetti Co-authors: Elena LIONETTI (1), Simona GATTI (1), Giulia NASPI CATASSI (2), Anil K VERMA (1), Francesco VALITUTTI (2), Antonella BELLANTONI (3), Linda BALANZONI (4), Mara CANANZI (4), Mauro CINQUETTI (4), Elisa D'ANGELO (5), Ruggiero FRANCAVILLA (6), Monica MONTUORI (2), Basilio MALAMISURA (5), Francesca PENAGINI (7), Chiara Maria TROVATO (2), Gian Vincenzo ZUCCOTTI (7), Carlo CATASSI (1) - (1)Università Politecnica delle Marche, Italie, (2)Università La Sapienza, Italie, (3)Bianchi Melacrino Morelli Hospital, Italie, (4)G Fracastoro Hospital, Italie, (5)Ospedale di Cava de Tirreni, Italie, (6)Università degli studi di Bari, Italie, (7)Università di Milano, Italie ABSTRACT CONTENT Objectives Celiac disease (CD) is one of the most common lifelong disorders, affecting approximately 1% of the population. Few data are available about possible recent changes of CD frequency. Currently, the preferred diagnostic strategy for CD is case- finding, with more than 50% of cases remaining undiagnosed because asymptomatic. We aimed to investigate: a) the current prevalence of CD in Italy by mass screening
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