Clinical similarities and differences of patients with X-linked lymphoproliferative syndrome type 1 (XLP-1/SAP deficiency) versus type 2 (XLP-2/XIAP deficiency).
Jana Pachlopnik Schmid
(1, 2)
,
Danielle Canioni
(3)
,
Despina Moshous
(1, 2, 3)
,
Fabien Touzot
(1, 2)
,
Nizar Mahlaoui
(1)
,
Fabian Hauck
(1, 2)
,
Hirokazu Kanegane
(4)
,
Eduardo Lopez-Granados
(5)
,
Ester Mejstrikova
(6)
,
Isabelle Pellier
(7)
,
Lionel Galicier
(8)
,
Claire Galambrun
(9)
,
Vincent Barlogis
(10)
,
Pierre Bordigoni
(11)
,
Alain Fourmaintraux
(12)
,
Mohamed A. Hamidou
(7)
,
Alain Dabadie
(13)
,
Françoise Le Deist
(2, 14)
,
Filomeen Haerynck
(15)
,
Marie Ouachée-Chardin
(16)
,
Pierre-Simon Rohrlich
(17)
,
Jean-Louis Stephan
(18)
,
Christelle Lenoir
(2)
,
Stéphanie Rigaud
(1, 2)
,
Nathalie Lambert
(2)
,
Michèle Milili
(19)
,
Claudin Schiff
(19)
,
Helen Chapel
(5)
,
Capucine Picard
(20, 21)
,
Geneviève de Saint Basile
(1, 2, 3)
,
Stéphane Blanche
(8)
,
Alain Fischer
(1, 2, 22, 23)
,
Sylvain Latour
(1, 2)
1
IRNEM -
IFR Necker-Enfants Malades
2 Developpement Normal et Pathologique du Système Immunitaire
3 Service d'anatomie pathologique [CHU Necker]
4 Graduate School of Medicine, University of Toyama
5 University of Oxford
6 Teaching Hospital Motol and 2nd Medical School, Charles University
7 CRCNA - Centre de Recherche en Cancérologie Nantes-Angers
8 Service d'immuno-hématologie pédiatrique [CHU Necker]
9 Service d'Hématologie pédiatrique, Hôpital de la Timone, Marseille
10 Service d'hématologie pédiatrique
11 CHRU Nancy - Centre Hospitalier Régional Universitaire de Nancy
12 GHSR - Groupe Hospitalier Sud Réunion
13 Centre Hospitalier Universitaire [Rennes]
14 CEREDIH - Centre de Référence Déficits Immunitaires Héréditaires
15 Department of Paediatric Pulmonology
16 Service d'hématologie et immunologie pédiatrique
17 Département de pédiatrie
18 Service d'hématologie pédiatrique
19 CIML - Centre d'Immunologie de Marseille - Luminy
20 Inserm U980 - Génétique Humaine des Maladies Infectieuses
21 Centre d'étude des Déficits Immunitaires
22 Assistance Publique-Hôpitaux de Paris, Service d'Immunologie et d'Hématologie Pédiatrique
23 Collège de France - Chaire Médecine expérimentale (A. Fischer)
2 Developpement Normal et Pathologique du Système Immunitaire
3 Service d'anatomie pathologique [CHU Necker]
4 Graduate School of Medicine, University of Toyama
5 University of Oxford
6 Teaching Hospital Motol and 2nd Medical School, Charles University
7 CRCNA - Centre de Recherche en Cancérologie Nantes-Angers
8 Service d'immuno-hématologie pédiatrique [CHU Necker]
9 Service d'Hématologie pédiatrique, Hôpital de la Timone, Marseille
10 Service d'hématologie pédiatrique
11 CHRU Nancy - Centre Hospitalier Régional Universitaire de Nancy
12 GHSR - Groupe Hospitalier Sud Réunion
13 Centre Hospitalier Universitaire [Rennes]
14 CEREDIH - Centre de Référence Déficits Immunitaires Héréditaires
15 Department of Paediatric Pulmonology
16 Service d'hématologie et immunologie pédiatrique
17 Département de pédiatrie
18 Service d'hématologie pédiatrique
19 CIML - Centre d'Immunologie de Marseille - Luminy
20 Inserm U980 - Génétique Humaine des Maladies Infectieuses
21 Centre d'étude des Déficits Immunitaires
22 Assistance Publique-Hôpitaux de Paris, Service d'Immunologie et d'Hématologie Pédiatrique
23 Collège de France - Chaire Médecine expérimentale (A. Fischer)
Fabien Touzot
- Function : Author
- PersonId : 762697
- ORCID : 0000-0002-0889-4905
Lionel Galicier
- Function : Author
- PersonId : 762207
- ORCID : 0000-0002-0360-7620
Vincent Barlogis
- Function : Author
- PersonId : 762453
- ORCID : 0000-0001-9645-3968
- IdRef : 108920046
Filomeen Haerynck
- Function : Author
- PersonId : 764610
- ORCID : 0000-0001-9161-7361
Capucine Picard
- Function : Author
- PersonId : 758297
- ORCID : 0000-0001-8788-5056
- IdRef : 091572363
Sylvain Latour
- Function : Author
- PersonId : 764611
- ORCID : 0000-0001-8238-4391
- IdRef : 117717886
Abstract
X-linked lymphoproliferative syndromes (XLP) are primary immunodeficiencies characterized by a particular vulnerability toward Epstein-Barr virus infection, frequently resulting in hemophagocytic lymphohistiocytosis (HLH). XLP type 1 (XLP-1) is caused by mutations in the gene SH2D1A (also named SAP), whereas mutations in the gene XIAP underlie XLP type 2 (XLP-2). Here, a comparison of the clinical phenotypes associated with XLP-1 and XLP-2 was performed in cohorts of 33 and 30 patients, respectively. HLH (XLP-1, 55%; XLP-2, 76%) and hypogammaglobulinemia (XLP-1, 67%; XLP-2, 33%) occurred in both groups. Epstein-Barr virus infection in XLP-1 and XLP-2 was the common trigger of HLH (XLP-1, 92%; XLP-2, 83%). Survival rates and mean ages at the first HLH episode did not differ for both groups, but HLH was more severe with lethal outcome in XLP-1 (XLP-1, 61%; XLP-2, 23%). Although only XLP-1 patients developed lymphomas (30%), XLP-2 patients (17%) had chronic hemorrhagic colitis as documented by histopathology. Recurrent splenomegaly often associated with cytopenia and fever was preferentially observed in XLP-2 (XLP-1, 7%; XLP-2, 87%) and probably represents minimal forms of HLH as documented by histopathology. This first phenotypic comparison of XLP subtypes should help to improve the diagnosis and the care of patients with XLP conditions.