TY - JOUR
T1 - Increased pro-inflammatory cytokine production after lipopolysaccharide stimulation in patients with X-linked agammaglobulinemia
AU - González-Serrano, María Edith
AU - Estrada-García, Iris
AU - Mogica-Martínez, Dolores
AU - González-Garay, Alejandro
AU - López-Herrera, Gabriela
AU - Berrón-Ruiz, Laura
AU - Espinosa-Padilla, Sara Elva
AU - Yamazaki-Nakashimada, Marco Antonio
AU - Vargas-Hernández, Alexander
AU - Santos-Argumedo, Leopoldo
AU - Estrada-Parra, Sergio Antonio
AU - Espinosa-Rosales, Francisco J.
N1 - Funding Information:
Acknowledgments The authors sincerely thank the patients and their families for their cooperation. This work was supported by the following foundations and institutions: Consejo Nacional de Ciencia y Tecnología (CONACYT, México), grants 56836 and 153733; Instituto de Ciencia y Tecnología del Distrito Federal grant ICYTDF/326/2009; “Fundación para niñas y niños con inmunodeficiencias primarias A.C.”. María Edith González Serrano and Alexander Vargas Hernández were fellows 207006 and 206710 from Conacyt respectively.
PY - 2012/10
Y1 - 2012/10
N2 - Purpose: 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-10. 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.
AB - Purpose: 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-10. 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.
KW - Bruton's tyrosine kinase
KW - Inflammatory response
KW - LPS signaling
KW - TIRAP
KW - X-linked agammaglobulinemia
UR - http://www.scopus.com/inward/record.url?scp=84866644659&partnerID=8YFLogxK
U2 - 10.1007/s10875-012-9706-z
DO - 10.1007/s10875-012-9706-z
M3 - Artículo
SN - 0271-9142
VL - 32
SP - 967
EP - 974
JO - Journal of Clinical Immunology
JF - Journal of Clinical Immunology
IS - 5
ER -