Title :

Genetic Diagnosis Guides Treatment of Autoimmune Enteropathy.

Author(s) :

Charbit-Henrion, Fabienne [Auteur]
Biodiversité et Biotechnologie Fongiques [BBF]
Haas, Manon [Auteur]
Imagine - Institut des maladies génétiques (IHU) [Imagine - U1163]
Chaussade, Stanislas [Auteur]
Hôpital Cochin [AP-HP]
Cellier, Christophe [Auteur]
Hôpital Européen Georges Pompidou [APHP] [HEGP]
Cerf-Bensussan, Nadine [Auteur]
Imagine - Institut des maladies génétiques (IHU) [Imagine - U1163]
Malamut, Georgia [Auteur]
Imagine - Institut des maladies génétiques (IHU) [Imagine - U1163]
Khater, Sherine [Auteur]
Hôpital Européen Georges Pompidou [APHP] [HEGP]
Khiat, Anis [Auteur]
Imagine - Institut des maladies génétiques (IHU) [Imagine - U1163]
Cording, Sascha [Auteur]
Imagine - Institut des maladies génétiques (IHU) [Imagine - U1163]
Parlato, Marianna [Auteur]
Imagine - Institut des maladies génétiques (IHU) [Imagine - U1163]
Dragon-Durey, Marie-Agnès [Auteur]
Hôpital Européen Georges Pompidou [APHP] [HEGP]
Beuvon, Frédéric [Auteur]
Hôpital Cochin [AP-HP]
Brousse, Nicole [Auteur]
Hôpital Necker - Enfants Malades [AP-HP]
Terris, Benoit [Auteur]
Hôpital Cochin [AP-HP]
Picard, Capucine [Auteur]
Hôpital Necker - Enfants Malades [AP-HP]
Fusaro, Mathieu [Auteur]
Hôpital Necker - Enfants Malades [AP-HP]
Rieux-Laucat, Frédéric [Auteur]
Stolzenberg, Marie-Claude [Auteur]
Jannot, Anne-Sophie [Auteur]
Hôpital Européen Georges Pompidou [APHP] [HEGP]
Mathian, Alexis [Auteur]
Allez, Matthieu [Auteur]
Hopital Saint-Louis [AP-HP] [AP-HP]
Malphettes, Marion [Auteur]
Fieschi, Claire [Auteur]
Hopital Saint-Louis [AP-HP] [AP-HP]
Aubourg, Alexandre [Auteur]
Centre Hospitalier Régional Universitaire de Tours [CHRU Tours]
Zallot, Camille [Auteur]
Centre Hospitalier Régional Universitaire de Nancy [CHRU Nancy]
Roblin, Xavier [Auteur]
Centre Hospitalier Universitaire de Saint-Etienne [CHU Saint-Etienne] [CHU ST-E]
Abitbol, Vered [Auteur]
Belle, Arthur [Auteur]
Hôpital Cochin [AP-HP]
Wils, Pauline [Auteur]
Institute for Translational Research in Inflammation - U 1286 [INFINITE]
Cheminant, Morgane [Auteur]
Hôpital Necker - Enfants Malades [AP-HP]
Matysiak-Budnik, Tamara [Auteur]
Hôtel-Dieu de Nantes
Vuitton, Lucine [Auteur]
Hôpital JeanMinjoz
Pouderoux, Philippe [Auteur]
Centre Hospitalier Universitaire de Nîmes [CHU Nîmes]
Abramowitz, Laurent [Auteur]
AP-HP - Hôpital Bichat - Claude Bernard [Paris]
Castelle, Martin [Auteur]
Hôpital Necker - Enfants Malades [AP-HP]
Suarez, Felipe [Auteur]
Hermine, Olivier [Auteur]
Hôpital Necker - Enfants Malades [AP-HP]
Ruemmele, Frank [Auteur]
Imagine - Institut des maladies génétiques [IMAGINE - U1163]
Mouthon, Luc [Auteur]
Centre de référence des maladies auto-immunes systémiques rares d'Île-de-France / National Reference Center for Rare Systemic Autoimmune Diseases

Journal title :

Clinical Gastroenterology and Hepatology

Abbreviated title :

Clin Gastroenterol Hepatol

Volume number :

21

Pages :

1368-1371

Publication date :

2022-10-03

ISSN :

1542-7714

English abstract : [en]

Autoimmune enteropathy (AIE) is a severe form of enteropathy characterized by chronic diarrhea refractory to any exclusion diet and associated with autoimmunity.1 ,2 Despite this clear definition, diagnosis is challenging. ...
Show more >Autoimmune enteropathy (AIE) is a severe form of enteropathy characterized by chronic diarrhea refractory to any exclusion diet and associated with autoimmunity.1 ,2 Despite this clear definition, diagnosis is challenging. The presence of antienterocyte antibodies against the AIE-75kDa antigen3 is a strong but inconstant biomarker. In a recent cohort of 40 AIE patients, anti-enterocyte antibodies were reported in only 14% (4/28) of the cases, likely caused by the high frequency of patients with primary hypogammaglobulinemia.2 Moreover patients may display celiac anti-transglutaminase antibodies.4 The common histopathologic presentation of AIE includes intestinal villous atrophy with variable lymphocytic infiltration and various features of follicular lymphoid hyperplasia, cryptitis, graft-versus-host disease-like lesions, and loss of Paneth and goblet cells.2 ,4 This mixed histopathologic pattern combined with inefficacy of gluten-free diet allow differentiating AIE from celiac disease.1 ,2 ,4 Treatment remains challenging because AIE patients are only variably improved by steroids and immunomodulators.4 Therefore, identification of the underlying molecular mechanism is crucial to treat unresponsive patients. Genetic studies have revealed that several monogenic inborn errors of immunity, notably NFKB1 (nuclear factor kappa B subunit 1), CTLA4 (cytotoxic T-lymphocyte-associated protein 4) haploinsufficiency, and LRBA (LPS responsive beige-like anchor protein) deficiency may manifest by AIE only at adulthood (reviewed in5 ). The latter finding prompted us to screen a cohort of 48 adult patients with AIE by next-generation sequencing (Supplementary Methods). Representative endoscopic findings and histologic features are shown in Figure 1A and B. Clinical features are summarized in Figure 1C. Malnutrition (body mass index <19), anemia, and primary immunoglobulin deficiency were present in 67% of cases. Small bowel inflammation consisted mainly in villous atrophy in 30/48 (63%), and intraepithelial and/or lamina propria lymphocytosis in 39/48 patients (81%). Intestinal lymphocytes had a normal phenotype and TCRγ rearrangements showed a polyclonal profile in intestinal biopsies except in 2 patients who developed intestinal CD4+ T-cell lymphoproliferations. Chronic gastritis and colitis were present in 39/48 patients (81%). Eight patients with primary hypogammaglobulinemia and abnormal hepatic tests and/or liver imaging had biopsy-proven nodular regenerative hyperplasia. Main peripheral blood abnormalities were lymphopenia (34/48), particularly B lymphopenia, in keeping with the high frequency of primary hypogammaglobulinemia.Show less >

Language :

Anglais

Audience :

Internationale

Popular science :

Non

Administrative institution(s) :

Université de Lille
Inserm
CHU Lille

Collections :

• Institut de Recherche Translationnelle sur l'Inflammation (INFINITE) - U1286

Submission date :

2024-02-01T22:08:16Z
2024-03-29T09:47:36Z