Combined Immunodeficiency in Patients With Trichohepatoenteric Syndrome

Frederic Vely (1) , Vincent Barlogis (2) , Evelyne Marinier (3) , Marie-Edith Coste (4) , Beatrice Dubern (5) , Emmanuelle Dugelay , Julie Lemale (5) , Christine Martinez-Vinson (6) , Noël Peretti (7) , Ariane Perry , Patrice Bourgeois (8, 9) , Catherine Badens (8, 9, 10) , Olivier Goulet (11, 12, 13, 14) , Jean-Pierre Hugot (15) , Catherine Farnarier (16) , Alexandre Fabre (4, 8)

1 CIML - Centre d'Immunologie de Marseille - Luminy
2 Service d'hématologie pédiatrique [AP-HM Hôpital de la Timone]
3 Department of Pediatric Gastroenterology
4 Service de pédiatrie multidisciplinaire [Hôpital de la Timone Enfants - APHM]
5 CHU Trousseau [APHP]
6 Service de gastroentérologie et nutrition pédiatrique
7 CarMeN - Cardiovasculaire, métabolisme, diabétologie et nutrition
8 MMG - Marseille medical genetics - Centre de génétique médicale de Marseille
9 Département de génétique médicale [Hôpital de la Timone - APHM]
10 Centre de référence maladie rare Thalassémie
11 IMAGINE - U1163 - Imagine - Institut des maladies génétiques
12 CHU Necker - Enfants Malades [AP-HP]
13 UPD5 - Université Paris Descartes - Paris 5
14 AP-HP - Assistance publique - Hôpitaux de Paris (AP-HP)
15 OSEB - Origine, structure et évolution de la biodiversité
16 LA CONCEPTION - Hôpital de la Conception [CHU - APHM]

The syndromic diarrhea/trichohepatoenteric syndrome (SD/THE) is a rare and multi-system genetic disorder caused by mutation in SKIV2L or in TTC37, two genes encoding subunits of the putative human SKI complex involved in RNA degradation. The main features are intractable diarrhea of infancy, hair abnormalities, facial dysmorphism, and intrauterine growth restriction. Immunologically this syndrome is associated with a hypogammaglobulinemia leading to an immunoglobulin supplementation. Our immune evaluation of a large French cohort of SD/THE patient revealed several immunological defects. First, switched memory B lymphocytes count is very low. Second, IFN-gamma production by T and NK cells is impaired and associated with a reduced degranulation of NK cells. Third, T cell proliferation was abnormal in 3/6 TTC37-mutated patients. These three patients present with severe EBV infection and a transient hemophagocytosis which may be related to these immunological defects. Moreover, an immunological screening of patients with clinical features of SD/THE could facilitate both diagnosis and therapeutic management of these patients.

Keywords: t cells; sKIV2L; ttC37; memory B cells; immunodeficiency; syndromic diarrhea/trichohepatoenteric syndrome; NK cells

Domains: Life Sciences [q-bio]; Genetics; Human genetics

Frederic Vely, Vincent Barlogis, Evelyne Marinier, Marie-Edith Coste, Beatrice Dubern, et al.. Combined Immunodeficiency in Patients With Trichohepatoenteric Syndrome. Frontiers in Immunology, 2018, 9, ⟨10.3389/fimmu.2018.01036⟩. ⟨hal-02000323⟩