Clinical similarities and differences of patients with X-linked lymphoproliferative syndrome type 1 (XLP-1/SAP deficiency) versus type 2 (XLP-2/XIAP deficiency).
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.
INSERM Unité 768, Laboratoire du Développement Normal et Pathologique du Système Immunitaire, Hôpital Necker-Enfants Malades, Paris, France.
Jana
J
Pachlopnik Schmid
Danielle
D
Canioni
Despina
D
Moshous
Fabien
F
Touzot
Nizar
N
Mahlaoui
Fabian
F
Hauck
Hirokazu
H
Kanegane
Eduardo
E
Lopez-Granados
Ester
E
Mejstrikova
Isabelle
I
Pellier
Lionel
L
Galicier
Claire
C
Galambrun
Vincent
V
Barlogis
Pierre
P
Bordigoni
Alain
A
Fourmaintraux
Mohamed
M
Hamidou
Alain
A
Dabadie
Françoise
F
Le Deist
Filomeen
F
Haerynck
Marie
M
Ouachée-Chardin
Pierre
P
Rohrlich
Jean-Louis
JL
Stephan
Christelle
C
Lenoir
Stéphanie
S
Rigaud
Nathalie
N
Lambert
Michèle
M
Milili
Claudin
C
Schiff
Helen
H
Chapel
Capucine
C
Picard
Geneviève
G
de Saint Basile
Stéphane
S
Blanche
Alain
A
Fischer
Sylvain
S
Latour
D000293:Adolescent; D000328:Adult; D000368:Aged; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D005260:Female; D006801:Humans; D007124:Immunoenzyme Techniques; D007223:Infant; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics*; D008232:Lymphoproliferative Disorders / Q000175:diagnosis* / Q000235:genetics / Q000628:therapy; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics; D010641:Phenotype; D012189:Retrospective Studies; D000071179:Signaling Lymphocytic Activation Molecule Associated Protein; D015996:Survival Rate; D051636:X-Linked Inhibitor of Apoptosis Protein / Q000235:genetics*; D055815:Young Adult
D047908:Intracellular Signaling Peptides and Proteins; C114953:SH2D1A protein, human; D000071179:Signaling Lymphocytic Activation Molecule Associated Protein; D051636:X-Linked Inhibitor of Apoptosis Protein; C496866:XIAP protein, human