Secretory IgA mediates retrotranscytosis of intact gliadin peptides via the transferrin receptor in celiac disease

Celiac disease (CD) is an enteropathy resulting from an abnormal immune response to gluten-derived peptides in genetically susceptible individuals. This immune response is initiated by intestinal transport of intact peptide 31-49 (p31-49) and 33-mer gliadin peptides through an unknown mechanism. We show that the transferrin receptor CD71 is responsible for apical to basal retrotranscytosis of gliadin peptides, a process during which p31-49 and 33-mer peptides are protected from degradation. In patients with active CD, CD71 is overexpressed in the intestinal epithelium and colocalizes with immunoglobulin (Ig) A. Intestinal transport of intact p31-49 and 33-mer peptides was blocked by polymeric and secretory IgA (SIgA) and by soluble CD71 receptors, pointing to a role of SIgA–gliadin complexes in this abnormal intestinal transport. This retrotranscytosis of SIgA–gliadin complexes may promote the entry of harmful gliadin peptides into the intestinal mucosa, thereby triggering an immune response and perpetuating intestinal inflammation. Our findings strongly implicate CD71 in the pathogenesis of CD

Feline low-grade alimentary lymphoma: an emerging entity and a potential animal model for human disease

Background: Low-grade alimentary lymphoma (LGAL) is characterised by the infiltration of neoplastic T-lymphocytes, typically in the small intestine. The incidence of LGAL has increased over the last ten years and it is now the most frequent digestive neoplasia in cats and comprises 60 to 75% of gastrointestinal lymphoma cases. Given that LGAL shares common clinical, paraclinical and ultrasonographic features with inflammatory bowel diseases, establishing a diagnosis is challenging. A review was designed to summarise current knowledge of the pathogenesis, diagnosis, prognosis and treatment of feline LGAL. Electronic searches of PubMed and Science Direct were carried out without date or language restrictions. Results: A total of 176 peer-reviewed documents were identified and most of which were published in the last twenty years. 130 studies were found from the veterinary literature and 46 from the human medicine literature. Heterogeneity of study designs and outcome measures made meta-analysis inappropriate. The pathophysiology of feline LGAL still needs to be elucidated, not least the putative roles of infectious agents, environmental factors as well as genetic events. The most common therapeutic strategy is combination treatment with prednisolone and chlorambucil, and prolonged remission can often be achieved. Developments in immunohistochemical analysis and clonality testing have improved the confidence of clinicians in obtaining a correct diagnosis between LGAL and IBD. The condition shares similarities with some diseases in humans, especially human indolent T-cell lymphoproliferative disorder of the gastrointestinal tract. Conclusions: The pathophysiology of feline LGAL still needs to be elucidated and prospective studies as well as standardisation of therapeutic strategies are needed. A combination of conventional histopathology and immunohistochemistry remains the current gold-standard test, but clinicians should be cautious about reclassifying cats previously diagnosed with IBD to lymphoma on the basis of clonality testing. Importantly, feline LGAL could be considered to be a potential animal model for indolent digestive T-cell lymphoproliferative disorder, a rare condition in human medicine

La maladie cœliaque

La maladie cœliaque est une entéropathie provoquée par l’ingestion de gluten chez des patients génétiquement prédisposés. Sa prévalence est estimée à 1 % en Europe et aux USA. Sa présentation clinique est extrêmement protéiforme et son diagnostic repose sur la présence d’anticorps sériques spécifiques et d’une atrophie villositaire intestinale. Le traitement repose sur un régime sans gluten à vie, qui permet de prévenir les complications osseuses, auto-immunes et malignes

Manisfestations digestives et hépatiques des déficits immunitaires communs variables

PARIS-BIUM (751062103) / SudocCentre Technique Livre Ens. Sup. (774682301) / SudocSudocFranceF

Validation of a French version of the quality of life "Celiac Disease Questionnaire".

BACKGROUND AND OBJECTIVE: Celiac disease (CD) is a common chronic autoimmune disorder. Both the manifestations of the disease and the burden of the compulsory life-long gluten-free diet (GFD) have been shown to be associated with impairment of health-related quality of life. The objectives of this study were to provide a cross-cultural adaptation of the specific quality of life "Celiac Disease Questionnaire" (CDQ) and to analyze its psychometric properties. MATERIALS AND METHODS: A cross-cultural French adaptation of the CDQ (F-CDQ) was obtained according to the revised international guidelines. The questionnaire was administered at baseline to 211 patients with biopsy proven CD followed-up in a single tertiary referral centre. The questionnaire was also administered after 7 days and 6 months. Reliability (intraclass correlation coefficients (ICC), Cronbach's alpha and Bland and Altman graphical analysis), validity (factorial structure and Rasch analysis, convergent validity), and responsiveness (effect size) of the F-CDQ were studied. RESULTS: The reliability of the F-CDQ was excellent with ICC and Cronbach's alpha coefficients being between 0.79 and 0.94 for the four subscales and the total score. The factorial structure and the Rasch analysis showed that the four dimensions of the original instrument were retained. Correlations with external measures (a generic measure of quality of life, an anxiety and depression instrument, a self-assessed disease severity, and clinical manifestations) were all in the expected direction confirming the validity of the instrument. Responsiveness was studied and effect sizes ≥ 0.20 were demonstrated for most of the subscales for patients who reported improvement or deterioration after 6 months. CONCLUSION: The F-CDQ retains the psychometric properties of the original instrument and should be useful in cross-national surveys and to assess outcome in clinical trials involving patients with CD

Management of immune checkpoint inhibitor in patients with cancer and pre-existing inflammatory bowel disease: Recommendations from the GETAID

International audienceBackground and aims: There is no consensus on the management of immune checkpoint inhibitor (ICI) for treating cancer in patients with pre-existing inflammatory bowel disease (IBD). The Groupe d'Étude Thérapeutique des Affections Inflammatoires du tube Digestif (GETAID) aimed to provide recommendations on this topic.Methods: A dedicated working group performed a comprehensive expert-based review of the literature, generated clinical key question and shaped recommendations that were further voted for approval by the educational and scientific committees of the GETAID. Using consensus methods, treatment modalities were defined by vote.Results: Majority of patients with IBD in clinical remission can be treated with ICI after cancer diagnosis. The rate of relapse or immune-related diarrhoea or colitis upon ICI treatment is up to 39.8% and is maximal with ICI combination therapy compared to monotherapies. When starting ICI in a patient with IBD, it is recommended to assess disease activity and pursue ongoing maintenance therapy. In case of relapse or immune-related diarrhoea or colitis upon ICI treatment, treatment depends on grading of diarrhoea or colitis and may include corticosteroid therapy, infliximab and/or vedolizumab.Conclusions: In the present publication, we provided recommendations, which may assist gastroenterologists, haematologists, and oncologists for a better management of patients with pre-existing IBD before and during cancer treatment with ICI

A novel data-driven workflow combining literature and electronic health records to estimate comorbidities burden for a specific disease: a case study on autoimmune comorbidities in patients with celiac disease

Abstract Background Data collected in EHRs have been widely used to identifying specific conditions; however there is still a need for methods to define comorbidities and sources to identify comorbidities burden. We propose an approach to assess comorbidities burden for a specific disease using the literature and EHR data sources in the case of autoimmune diseases in celiac disease (CD). Methods We generated a restricted set of comorbidities using the literature (via the MeSH® co-occurrence file). We extracted the 15 most co-occurring autoimmune diseases of the CD. We used mappings of the comorbidities to EHR terminologies: ICD-10 (billing codes), ATC (drugs) and UMLS (clinical reports). Finally, we extracted the concepts from the different data sources. We evaluated our approach using the correlation between prevalence estimates in our cohort and co-occurrence ranking in the literature. Results We retrieved the comorbidities for 741 patients with CD. 18.1% of patients had at least one of the 15 studied autoimmune disorders. Overall, 79.3% of the mapped concepts were detected only in text, 5.3% only in ICD codes and/or drugs prescriptions, and 15.4% could be found in both sources. Prevalence in our cohort were correlated with literature (Spearman’s coefficient 0.789, p = 0.0005). The three most prevalent comorbidities were thyroiditis 12.6% (95% CI 10.1–14.9), type 1 diabetes 2.3% (95% CI 1.2–3.4) and dermatitis herpetiformis 2.0% (95% CI 1.0–3.0). Conclusion We introduced a process that leveraged the MeSH terminology to identify relevant autoimmune comorbidities of the CD and several data sources from EHRs to phenotype a large population of CD patients. We achieved prevalence estimates comparable to the literature