A neuropathological study of cerebrovascular abnormalities in a signal transducer and activator of transcription 3–deficient patient

Marie-Olivia Chandesris (1, 2) , Françoise Gray (3, 4) , Patrick Bruneval (5, 6) , Arshid Azarine (7, 8) , Nathalie Boddaert (9) , Catherine Oppenheim (10) , François Paraire (11, 12) , Emmanuel Touzé (13) , Damien Bonnet (14) , Olivier Hermine (15) , Olivier Lortholary (16, 17, 18) , Valérie Cormier-Daire (19) , Pierre Boutouyrie (20) , Ziad Mallat (20, 21) , Alain Fischer (19, 2, 22) , Capucine Picard (19, 2, 23)

1 UPD5 - Université Paris Descartes - Paris 5
2 Hôpital Necker - Enfants Malades [AP-HP]
3 Hôpital Lariboisière-Fernand-Widal [APHP]
4 UPD7 - Université Paris Diderot - Paris 7
5 PARCC (UMR_S 970/ U970) - Paris-Centre de Recherche Cardiovasculaire
6 Département de Pathologie [AP-HP Hôpital Européen Georges Pompidou]
7 LIB - Laboratoire d'Imagerie Biomédicale [Paris]
8 Service de radiologie cardio-vasculaire [CHU HEGP]
9 Service de radiologie pédiatrique [CHU Necker]
10 U894 - Centre de Psychiatrie et Neurosciences
11 Hôpital Raymond Poincaré (Garches) [GHU AP-HP Université Paris-Saclay]
12 UVSQ - Université de Versailles Saint-Quentin-en-Yvelines
13 Sérine protéases et physiopathologie de l'unité neurovasculaire
14 M3C - Centre de Référence des cardiopathies congénitales
15 Service d'immuno-hématologie pédiatrique [CHU Necker]
16 CEREDIH - Centre de Référence Déficits Immunitaires Héréditaires
17 Centre d'infectiologie Necker-Pasteur [CHU Necker]
18 CNRMA - Centre National de Référence des Mycoses invasives et antifongiques - Mycologie moléculaire
19 IMAGINE - U1163 - Imagine - Institut des maladies génétiques
20 PARCC - UMR-S U970 - Paris-Centre de Recherche Cardiovasculaire
21 CAM - University of Cambridge [UK]
22 Collège de France - Chaire Médecine expérimentale (A. Fischer)
23 the Study Center of Primary Immunodeficiencies

Human signal transducer and activator of transcription 3 (STAT3) deficiency (Online Mendelian Inheritance in Man [OMIM] no. 147060) is a rare primary immunodeficiency caused by heterozygous mutations of STAT3, conferring susceptibility to infections and skeletal and connective tissues features. Recent morphologic data revealed that STAT3 deficiency is responsible for a diffuse vasculopathy,1, 2, 3, 4 which is characterized by alteration in mechanotransduction in the arterial wall causing hypotrophic remodeling despite increased forces exerting on the wall (circumferential wall stress), leading to enhanced susceptibility to aneurysm. The high vascular risk of such lesions was confirmed by the sudden death of a 35-year-old patient (carrying a missense F384L STAT3 mutation) after rupture of a giant basilar artery aneurysm (see Fig E1 in this article's Online Repository at www.jacionline.org). After consent of his family, an autopsy was performed 24 hours after death.

Keywords: STAT3 TRANSCRIPTION FACTOR; Vascular disease; Immune deficiency; Connective tissue disease

Domains: Life Sciences [q-bio]

Marie-Olivia Chandesris, Françoise Gray, Patrick Bruneval, Arshid Azarine, Nathalie Boddaert, et al.. A neuropathological study of cerebrovascular abnormalities in a signal transducer and activator of transcription 3–deficient patient. Journal of Allergy and Clinical Immunology, 2015, 136 (5), pp.1418-1421.e5. ⟨10.1016/j.jaci.2015.05.021⟩. ⟨hal-04331812⟩