Increased pro-inflammatory cytokine production after lipopolysaccharide stimulation in patients with X-linked agammaglobulinemia.
OBJECTIVE
To evaluate the lipopolysaccharide (LPS)-induced pro-inflammatory cytokine response by peripheral blood mononuclear cells (PBMCs) from XLA patients.


METHODS
Thirteen patients with XLA were included in the study. LPS-induced TNF-α, IL-1β, IL-6, and IL-10 production was determined in PBMCs from patients and matched healthy controls by ELISA. Cytokine production was correlated with the severity of mutation, affected domain and clinical characteristics.


RESULTS
In response to LPS, PBMCs from XLA patients produced significantly higher amounts of pro-inflammatory cytokines and IL-10 compared to controls, and this production was influenced neither by the severity of the mutation nor the affected domain. PBMCs from patients with a history of more hospital admissions before their diagnosis produced higher levels of TNF-α. PBMCs from patients with lower serum IgA levels showed a higher production of TNF-α and IL-1β. Less severe (punctual) mutations in the Btk gene were associated with higher serum IgG levels at diagnosis.


CONCLUSIONS
Our results demonstrate a predominantly inflammatory response in XLA patients after LPS stimulation and suggest a deregulation of TLR signaling in the absence of Btk. This response may be influenced by environmental factors.
Immunodeficiency Research Unit, National Institute of Pediatrics (INP), Av. Imán # 1, Col. Insurgentes Cuicuilco, Deleg. Coyoacán, Mexico City, ZP 04530, Mexico.
María Edith
ME
González-Serrano
Iris
I
Estrada-García
Dolores
D
Mogica-Martínez
Alejandro
A
González-Garay
Gabriela
G
López-Herrera
Laura
L
Berrón-Ruiz
Sara Elva
SE
Espinosa-Padilla
Marco Antonio
MA
Yamazaki-Nakashimada
Alexander
A
Vargas-Hernández
Leopoldo
L
Santos-Argumedo
Sergio Antonio
SA
Estrada-Parra
Francisco J
FJ
Espinosa-Rosales
D000293:Adolescent; D000328:Adult; D000077329:Agammaglobulinaemia Tyrosine Kinase; D000361:Agammaglobulinemia / Q000235:genetics / Q000276:immunology*; D001402:B-Lymphocytes / Q000276:immunology; D016022:Case-Control Studies; D002478:Cells, Cultured; D002648:Child; D016207:Cytokines / Q000276:immunology*; D040181:Genetic Diseases, X-Linked / Q000235:genetics / Q000276:immunology*; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000276:immunology*; D008070:Lipopolysaccharides / Q000276:immunology; D008297:Male; D009154:Mutation; D011505:Protein-Tyrosine Kinases / Q000235:genetics* / Q000276:immunology; D051197:Toll-Like Receptor 4 / Q000276:immunology; D055815:Young Adult
D016207:Cytokines; D008070:Lipopolysaccharides; C495345:TLR4 protein, human; D051197:Toll-Like Receptor 4; D011505:Protein-Tyrosine Kinases; D000077329:Agammaglobulinaemia Tyrosine Kinase; C000625949:BTK protein, human