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

被引：14

作者：

Bloch, Coralie ^{[1
,2
,3
,4
,5
,27
]}

Jais, Jean Philippe ^{[5
,6
,7
]}

Gil, Marine ^{[5
]}

Boubaya, Marouane ^{[1
]}

Lepelletier, Yves ^{[3
,5
]}

Bader-Meunier, Brigitte ^{[5
,8
]}

Mahlaoui, Nizar ^{[4
,5
,8
]}

Garcelon, Nicolas ^{[5
]}

Lambotte, Olivier ^{[9
]}

Launay, David ^{[10
,11
,12
]}

Larroche, Claire ^{[13
]}

Lazaro, Estibaliz ^{[14
,15
]}

Liffermann, Francois ^{[16
]}

Lortholary, Olivier ^{[4
,5
,17
]}

Michel, Marc ^{[18
]}

Michot, Jean-Marie ^{[19
]}

Morel, Pierre ^{[20
]}

Cheminant, Morgane ^{[3
,4
,5
,21
]}

Suarez, Felipe ^{[3
,4
,5
,21
]}

Terriou, Louis ^{[10
,11
,12
]}

Urbanski, Geoffrey ^{[22
,23
]}

Viallard, Jean -Francois ^{[14
]}

Alcais, Alexandre ^{[5
,6
,7
]}

Fischer, Alain ^{[4
,5
,8
,24
,25
,26
]}

Basile, Genevieve de Saint ^{[4
,5
,24
]}

Hermine, Olivier ^{[3
,4
,5
,21
,27
]}

机构：

[1] Avicenne Univ Hosp, AP HP, Clin Res Unit, Bobigny, France

[2] Paris 13 Univ, Sorbonne Paris Cite, Paris, France

[3] CNRS URL 8254, INSERM UMR1163, Lab Cellular & Mol Mech Hematol Disorders & Therap, Paris, France

[4] Necker Univ Hosp, AP HP, French Natl Ctr Primary Immunodeficiencies, Paris, France

[5] Univ Paris Cite, Imagine Inst, Paris, France

[6] Necker Univ Hosp, Biostat Unit, AP HP, Paris, France

[7] Necker Univ Hosp, AP HP, UMR1163, Paris, France

[8] Necker Univ Hosp, AP HP, Dept Pediat Immunol & Rheumatol, Paris, France

[9] Univ Paris Saclay, Hop Bicetre, AP HP, IMVAHB UMR1184,INSERM,CEA, Le Kremlin Bicetre, France

[10] Univ Lille, CRC SEP Lille, Lille, France

[11] Ctr Reference Malad Autoimmunes Syst Rares Nord &, Dept Med Interne & Immunol Clin, Lille, France

[12] INSERM INFINITE U1286, F-59000 Lille, France

[13] Avicenne Hosp, AP HP, Internal Med Unit, Bobigny, France

[14] Bordeaux Hosp Univ, Internal Med Dept, Bordeaux, France

[15] CNRS UMR 5164 Immuno ConEpT, Bordeaux, France

[16] Ctr Hosp Dax, Serv Med Internehematol, Dax, France

[17] Univ Paris, Hop Necker Enfants Malad, AP HP, Serv Malad Infect & Trop,Ctr Infectiol Necker Past, Paris, France

[18] Univ Paris Est Creteil, Ctr Reference Malad Rares Sur Cytopenies Autoimmun, Dept Internal Med, Hop Univ Henri Mondor,AP HP, Creteil, France

[19] Univ Paris Saclay, Drug Dev Dept, Gustave Roussy, Villejuif, France

[20] Hop Schaffner Lens, Serv Hematol Clin, Lens, France

[21] Necker Univ Hosp, AP HP, Clin Hematol, Paris, France

[22] Univ Hosp, Dept Internal Med & Clin Immunol, Angers, France

[23] Univ Angers, MITOVASC Inst, MitoLab Team, UMR CNRS 6015,INSERM U1083, Angers, France

[24] INSERM, Lab Normal & Pathol Homeostasis Immune Syst, UMR1163, Paris, France

[25] Necker Univ Hosp, Dept Hematol, Paris, France

[26] Coll France, Paris, France

[27] INSERM, U1163, Inst IMAGINE, Lab 215 217,CNRS ERL 8254, 24 Blvd Montparnasse, F-75015 Paris, France

来源：

JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY | 2024年 / 153卷 / 01期

关键词：

Hemophagocytic lymphohistiocytosis (HLH); HLH- related gene variants; adult secondary HLH; severe HLH in adults; MUTATIONS; CYTOTOXICITY; ONSET; PRF1; IDENTIFICATION; PATHOGENESIS; DIAGNOSIS; MUNC13-4; REVEALS; STXBP2;

D O I：

10.1016/j.jaci.2023.07.023

中图分类号：

R392 [医学免疫学];

学科分类号：

100102 ;

摘要：

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. (J Allergy Clin Immunol 2024;153:256-64.)

引用

页码：256 / 264

页数：9

共 60 条

[1]

Arico M, 1996, LEUKEMIA, V10, P197

[2] Identification of the homologous beige and Chediak-Higashi syndrome genes [J].