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

Autor:	Bloch C; Clinical Research Unit, Avicenne University Hospital, AP-HP, Bobigny, France; Paris 13 University, Sorbonne Paris Cité, Paris, France; Laboratory of Cellular and Molecular Mechanisms of Hematological Disorders and Therapeutical Implications, INSERM UMR1163/CNRS URL 8254, Paris, France; French National Center for Primary Immunodeficiencies, Necker University Hospital, AP-HP, Paris, France; Imagine Institute, Université Paris Cité, Paris, France. Electronic address: coralie.bloch-queyrat@aphp.fr., Jais JP; Imagine Institute, Université Paris Cité, Paris, France; Biostatistic Unit, Necker University Hospital, AP-HP, Paris, France; Human Genetics of Infectious Diseases: Complex Predisposition, INSERM UMR1163, Paris, France., Gil M; Imagine Institute, Université Paris Cité, Paris, France., Boubaya M; Clinical Research Unit, Avicenne University Hospital, AP-HP, Bobigny, France., Lepelletier Y; Laboratory of Cellular and Molecular Mechanisms of Hematological Disorders and Therapeutical Implications, INSERM UMR1163/CNRS URL 8254, Paris, France; Imagine Institute, Université Paris Cité, Paris, France., Bader-Meunier B; Imagine Institute, Université Paris Cité, Paris, France; Department of Pediatric Immunology and Rheumatology, Necker University Hospital, AP-HP, Paris, France., Mahlaoui N; French National Center for Primary Immunodeficiencies, Necker University Hospital, AP-HP, Paris, France; Imagine Institute, Université Paris Cité, Paris, France; Department of Pediatric Immunology and Rheumatology, Necker University Hospital, AP-HP, Paris, France., Garcelon N; Imagine Institute, Université Paris Cité, Paris, France., Lambotte O; University Paris Saclay, AP-HP, Hôpital Bicêtre, IMVAHB UMR1184, INSERM, CEA, Le Kremlin Bicêtre, France., Launay D; Université de Lille, CHU Lille, Département de Médecine Interne et Immunologie Clinique, Centre de Référence des Maladies Auto-immunes Systémiques Rares du Nord et Nord-Ouest de France, Lille, France; INSERM INFINITE U1286, Lille, France., Larroche C; Internal Medicine Unit, Avicenne Hospital, AP-HP, Bobigny, France., Lazaro E; Internal Medicine Department, Bordeaux Hospital University, Bordeaux, France; CNRS-UMR 5164 Immuno ConcEpT, Bordeaux, France., Liffermann F; Service de medecine interne-hematologie, Centre hospitalier de Dax, Dax, France., Lortholary O; French National Center for Primary Immunodeficiencies, Necker University Hospital, AP-HP, Paris, France; Imagine Institute, Université Paris Cité, Paris, France; Service de Maladies Infectieuses et Tropicales, Centre d'Infectiologie Necker Pasteur, Hôpital Universitaire Necker-Enfants Malades, Assistance Publique-Hôpitaux de Paris, Université de Paris, Paris, France., Michel M; Department of Internal Medicine, Centre de Référence maladies rares sur les Cytopénies Auto-Immunes de l'adulte, Hôpitaux Universitaires Henri Mondor, AP-HP, Université Paris-Est Créteil, Créteil, France., Michot JM; Gustave Roussy, University Paris Saclay, Drug Development Department, Villejuif, France., Morel P; Service d'Hématologie Clinique, Hôpital Schaffner de Lens, Lens Cedex, France., Cheminant M; Laboratory of Cellular and Molecular Mechanisms of Hematological Disorders and Therapeutical Implications, INSERM UMR1163/CNRS URL 8254, Paris, France; French National Center for Primary Immunodeficiencies, Necker University Hospital, AP-HP, Paris, France; Imagine Institute, Université Paris Cité, Paris, France; Clinical Hematology, Necker University Hospital, AP-HP, Paris, France., Suarez F; Laboratory of Cellular and Molecular Mechanisms of Hematological Disorders and Therapeutical Implications, INSERM UMR1163/CNRS URL 8254, Paris, France; French National Center for Primary Immunodeficiencies, Necker University Hospital, AP-HP, Paris, France; Imagine Institute, Université Paris Cité, Paris, France; Clinical Hematology, Necker University Hospital, AP-HP, Paris, France., Terriou L; Université de Lille, CHU Lille, Département de Médecine Interne et Immunologie Clinique, Centre de Référence des Maladies Auto-immunes Systémiques Rares du Nord et Nord-Ouest de France, Lille, France; INSERM INFINITE U1286, Lille, France., Urbanski G; Department of Internal Medicine and Clinical Immunology, University Hospital, Angers, France; MitoLab Team, MITOVASC Institute, UMR CNRS 6015, INSERM U1083, University of Angers, Angers, France., Viallard JF; Internal Medicine Department, Bordeaux Hospital University, Bordeaux, France., Alcais A; Imagine Institute, Université Paris Cité, Paris, France; Biostatistic Unit, Necker University Hospital, AP-HP, Paris, France; Human Genetics of Infectious Diseases: Complex Predisposition, INSERM UMR1163, Paris, France., Fischer A; French National Center for Primary Immunodeficiencies, Necker University Hospital, AP-HP, Paris, France; Imagine Institute, Université Paris Cité, Paris, France; Department of Pediatric Immunology and Rheumatology, Necker University Hospital, AP-HP, Paris, France; Laboratory of Normal and Pathological Homeostasis of the Immune System, INSERM UMR1163, Paris, France; Necker University Hospital, AP-HP, Paris, France; College de France, Paris, France., de Saint Basile G; French National Center for Primary Immunodeficiencies, Necker University Hospital, AP-HP, Paris, France; Imagine Institute, Université Paris Cité, Paris, France; Laboratory of Normal and Pathological Homeostasis of the Immune System, INSERM UMR1163, Paris, France., Hermine O; Laboratory of Cellular and Molecular Mechanisms of Hematological Disorders and Therapeutical Implications, INSERM UMR1163/CNRS URL 8254, Paris, France; French National Center for Primary Immunodeficiencies, Necker University Hospital, AP-HP, Paris, France; Imagine Institute, Université Paris Cité, Paris, France; Clinical Hematology, Necker University Hospital, AP-HP, Paris, France. Electronic address: ohermine@gmail.com.
Jazyk:	angličtina
Zdroj:	The Journal of allergy and clinical immunology [J Allergy Clin Immunol] 2024 Jan; Vol. 153 (1), pp. 256-264. Date of Electronic Publication: 2023 Sep 09.
DOI:	10.1016/j.jaci.2023.07.023
Abstrakt:	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. (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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