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Increased Pro-inflammatory Cytokine Production After Lipopolysaccharide Stimulation in Patients with X-linked Agammaglobulinemia

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Abstract

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-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.

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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.

Conflict of Interest

The authors declare that they have no conflict of interest.

Author information

Authors and Affiliations

  1. Immunodeficiency Research Unit, National Institute of Pediatrics (INP), Av. Imán # 1, Col. Insurgentes Cuicuilco, Deleg. Coyoacán, Mexico City, ZP 04530, Mexico

    María Edith González-Serrano, Gabriela López-Herrera, Laura Berrón-Ruiz, Sara Elva Espinosa-Padilla & Francisco J. Espinosa-Rosales

  2. Department of Immunology, INP, Av. Imán # 1, Col. Insurgentes Cuicuilco, Deleg. Coyoacán, Mexico City, ZP 04530, Mexico

    Marco Antonio Yamazaki-Nakashimada

  3. Department of Research Methodology, INP, Av. Imán # 1, Col. Insurgentes Cuicuilco, Deleg. Coyoacán, Mexico City, ZP 04530, Mexico

    Alejandro González-Garay

  4. Department of Allergy, Medical Center “La Raza”, Mexican Social Security Institute, Calzada Vallejo y Av Jacarandas s/n, Col. La Raza, Deleg Azcapotzalco, ZP 02990, Mexico

    Dolores Mogica-Martínez

  5. Department of Molecular Biomedicine, Center for Research and Advanced Studies (CINVESTAV-IPN), Av. Instituto Politécnico Nacional No 2508, Col. San Pedro Zacatenco, Deleg. Gustavo A. Madero, México City, ZP, 07360, Mexico

    Gabriela López-Herrera, Laura Berrón-Ruiz, Alexander Vargas-Hernández & Leopoldo Santos-Argumedo

  6. National School of Biological Sciences, National Polytechnic Institute, Plan de Ayala y Prolongación de Carpio s/n, Col Santo Tomás, Deleg. Miguel Hidalgo, México City, ZP 11340, Mexico

    María Edith González-Serrano, Iris Estrada-García & Sergio Antonio Estrada-Parra

  7. Unidad de Investigación en Inmunodeficiencias, Instituto Nacional de Pediatría, Av. Del Imán # 1, Col. Insurgentes Cuicuilco, Delegación Coyoacán, CP 04530, Mexico City, Mexico

    Francisco J. Espinosa-Rosales

Authors
  1. María Edith González-Serrano
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  2. Iris Estrada-García
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  3. Dolores Mogica-Martínez
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  4. Alejandro González-Garay
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  5. Gabriela López-Herrera
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  6. Laura Berrón-Ruiz
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  7. Sara Elva Espinosa-Padilla
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  8. Marco Antonio Yamazaki-Nakashimada
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  9. Alexander Vargas-Hernández
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  10. Leopoldo Santos-Argumedo
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  11. Sergio Antonio Estrada-Parra
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  12. Francisco J. Espinosa-Rosales
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Corresponding author

Correspondence to Francisco J. Espinosa-Rosales.

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González-Serrano, M.E., Estrada-García, I., Mogica-Martínez, D. et al. Increased Pro-inflammatory Cytokine Production After Lipopolysaccharide Stimulation in Patients with X-linked Agammaglobulinemia. J Clin Immunol 32, 967–974 (2012). https://doi.org/10.1007/s10875-012-9706-z

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  • DOI: https://doi.org/10.1007/s10875-012-9706-z

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