Title :

Severe adult haemophagocytic lymphohistiocytosis (HLHa) correlates with HLH-related gene variants.

Author(s) :

Bloch, Coralie [Auteur]
Hôpital Necker - Enfants Malades [AP-HP]
Imagine - Institut des maladies génétiques (IHU) [Imagine - U1163]
Mécanismes cellulaires et moléculaires des désordres hématologiques et implications thérapeutiques = Molecular mechanisms of hematological disorders and therapeutic implications [ERL 8254]
Hôpital Avicenne [AP-HP]
Jais, Jean-Philippe [Auteur]
Hôpital Necker - Enfants Malades [AP-HP]
Imagine - Institut des maladies génétiques (IHU) [Imagine - U1163]
Gil, Marine [Auteur]
Imagine - Institut des maladies génétiques [IMAGINE - U1163]
Boubaya, Marouane [Auteur]
Hôpital Avicenne [AP-HP]
Lepelletier, Yves [Auteur]
Imagine - Institut des maladies génétiques (IHU) [Imagine - U1163]
Bader-Meunier, Brigitte [Auteur]
Hôpital Necker - Enfants Malades [AP-HP]
Imagine - Institut des maladies génétiques (IHU) [Imagine - U1163]
Mahlaoui, Nizar [Auteur]
Hôpital Necker - Enfants Malades [AP-HP]
Imagine - Institut des maladies génétiques (IHU) [Imagine - U1163]
Garcelon, Nicolas [Auteur]
Imagine - Institut des maladies génétiques (IHU) [Imagine - U1163]
Lambotte, Olivier [Auteur]

Launay, David [Auteur]
Institut de Recherche Translationnelle sur l'Inflammation (INFINITE) - U1286
Centre National de Référence des Maladies Auto-Immunes Systémiques Rares du Nord et Nord-Ouest de France [CeRAINO]
Larroche, Claire [Auteur]
Hôpital Avicenne [AP-HP]
Lazaro, Estibaliz [Auteur]
Immunology from Concept and Experiments to Translation = Immunologie Conceptuelle, Expérimentale et Translationnelle [ImmunoConcept]
Centre Hospitalier Universitaire de Bordeaux [CHU Bordeaux]
Liffermann, François [Auteur]
Centre Hospitalier de Dax
Lortholary, Olivier [Auteur]
Hôpital Necker - Enfants Malades [AP-HP]
Imagine - Institut des maladies génétiques (IHU) [Imagine - U1163]
Michel, Marc [Auteur]
Hôpital Henri Mondor
Michot, Jean-Marie [Auteur]
Université Paris-Saclay
Morel, Pierre [Auteur]
Centre Hospitalier de Lens
Cheminant, Morgane [Auteur]
Hôpital Necker - Enfants Malades [AP-HP]
Imagine - Institut des maladies génétiques (IHU) [Imagine - U1163]
Mécanismes cellulaires et moléculaires des désordres hématologiques et implications thérapeutiques = Molecular mechanisms of hematological disorders and therapeutic implications [ERL 8254]
Suarez, Felipe [Auteur]
Hôpital Necker - Enfants Malades [AP-HP]
Imagine - Institut des maladies génétiques (IHU) [Imagine - U1163]
Mécanismes cellulaires et moléculaires des désordres hématologiques et implications thérapeutiques = Molecular mechanisms of hematological disorders and therapeutic implications [ERL 8254]
Terriou, Louis [Auteur]
Institute for Translational Research in Inflammation - U 1286 [INFINITE]
Centre National de Référence des Maladies Auto-Immunes Systémiques Rares du Nord et Nord-Ouest de France [CeRAINO]
Urbanski, Geoffrey [Auteur]
MitoVasc - Physiopathologie Cardiovasculaire et Mitochondriale [MITOVASC]
Centre Hospitalier Universitaire d'Angers [CHU Angers]
Viallard, Jean-Francois [Auteur]
Centre Hospitalier Universitaire de Bordeaux [CHU Bordeaux]
Alcais, Alexandre [Auteur]
Hôpital Necker - Enfants Malades [AP-HP]
Imagine - Institut des maladies génétiques (IHU) [Imagine - U1163]
Human genetics of infectious diseases: Complex predisposition [Equipe Inserm U1163]
Fischer, Alain [Auteur]
Collège de France [CdF (institution)]
Hôpital Necker - Enfants Malades [AP-HP]
Imagine - Institut des maladies génétiques (IHU) [Imagine - U1163]
De Saint Basile, Geneviève [Auteur]
Hôpital Necker - Enfants Malades [AP-HP]
Imagine - Institut des maladies génétiques (IHU) [Imagine - U1163]
Hermine, Olivier [Auteur]
Hôpital Necker - Enfants Malades [AP-HP]
Imagine - Institut des maladies génétiques (IHU) [Imagine - U1163]

Journal title :

Journal of Allergy and Clinical Immunology

Abbreviated title :

J Allergy Clin Immunol

Publication date :

2023-09-09

ISSN :

1097-6825

HAL domain(s) :

Sciences du Vivant [q-bio]

English abstract : [en]

Background The contribution of genetic factors to the severity of adult hemophagocytic lymphohistiocytosis (HLHa) remains unclear. Objective We sought to assess a potential link between HLHa outcomes and HLH-related ...
Show more >Background The contribution of genetic factors to the severity of adult hemophagocytic lymphohistiocytosis (HLHa) remains unclear. Objective We sought to assess a potential link between HLHa outcomes and HLH-related gene variants. Methods Clinical characteristics of 130 HLHa patients (age ≥ 18 years and HScore ≥ 169) and genotype of 8 HLH-related genes (LYST, PRF1, UNC13-D, STX11, STXBP2, RAB27A, XIAP, and SAP) were collected. A total of 34 variants found in only 6 genes were selected on the basis of their frequency and criteria predicted to impair protein function. Severity was defined by refractory disease to HLH treatment, death, or transfer to an intensive care unit. Results HLHa-associated diseases (ADs) were neoplasia (n = 49 [37.7%]), autoimmune/inflammatory disease (n = 33 [25.4%]), or idiopathic when no AD was identified (n = 48 [36.9%]). Infectious events occurred in 76 (58.5%) patients and were equally distributed in all ADs. Severe and refractory HLHa were observed in 80 (61.5%) and 64 (49.2%) patients, respectively. HScore, age, sex ratio, AD, and infectious events showed no significant association with HLHa severity. Variants were identified in 71 alleles and were present in 56 (43.1%) patients. They were distributed as follows: 44 (34.4%), 9 (6.9%), and 3 (2.3%) patients carrying 1, 2, and 3 variant alleles, respectively. In a logistic regression model, only the number of variants was significantly associated with HLHa severity (1 vs 0: 3.86 [1.73-9.14], P = .0008; 2-3 vs 0: 29.4 [3.62-3810], P = .0002) and refractoriness (1 vs 0: 2.47 [1.17-5.34], P = .018; 2-3 vs 0: 13.2 [2.91-126.8], P = .0003). Conclusions HLH-related gene variants may be key components to the severity and refractoriness of HLHa.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 :

2024-01-11T22:15:13Z
2024-03-08T13:00:46Z