Interleukin 12 deficiency associated with recurrent infections

Soichi Haraguchi, Noorbibi K. Day, Robert Nelson, Patricia Emmanuel, John E. Duplantier, Christodoulos S. Christodoulou, Robert A. Good

Research output: Contribution to journalArticle

75 Citations (Scopus)

Abstract

A 3-yr-old female patient exhibited interleukin 12 (IL-12) deficiency that was associated with recurrent episodes of pneumococcal pneumonia with sepsis and other infections in the absence of fevers. The patient's peripheral blood mononuclear cells (PBMCs) exhibited normal proliferative responses to antigens. Immune responses, including in vivo production of antibodies to diphtheria, tetanus, or pneumococcal antigens, were normal. Ig levels and B cell and T cell phenotypes were also normal. In contrast, IL-12 p70 heterodimer production was undetectable by using supernatants of the patient's stimulated PBMCs when compared with control cells treated similarly. Although present, interferon γ (IFN-γ,) was reduced. The addition of recombinant IFN-γ to control cells enhanced the production of IL-12 by up to sixfold. By contrast, IL-12 was undetectable in supernatants of the patient's cells in the presence of recombinant IFN-γ. IL-12 p40 subunit mRNA by using the patient's PBMCs after stimulation with Staphylococcus aureus Cowan strain 1 or lipopolysaccharide was also undetectable by reverse transcription-PCR when compared with control cells. Production of IL-2, IL-6, tumor necrosis factor α, or IFN-γ of the patient's PBMCs after appropriate stimulation was observed. This patient has either a defect in Staphylococcus aureus Cowan strain 1-lipopolysaccharide- or staphylococcal enterotoxin A-induced signaling pathways for the activation of IL-12 p40 gene expression, or an abnormality in the IL-12 p40 gene itself.

Original languageEnglish (US)
Pages (from-to)13125-13129
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume95
Issue number22
DOIs
StatePublished - Oct 27 1998
Externally publishedYes

Fingerprint

Interleukin-12
Infection
Blood Cells
Lipopolysaccharides
Staphylococcus aureus
Interleukin-12 Subunit p40
Pneumococcal Pneumonia
Antigens
Diphtheria
Tetanus
Interferons
Reverse Transcription
Antibody Formation
Interleukin-2
Interleukin-6
Sepsis
B-Lymphocytes
Fever
Tumor Necrosis Factor-alpha
T-Lymphocytes

Keywords

  • Immunodeficiency
  • Interleukin 12
  • Pneumonia

ASJC Scopus subject areas

  • Genetics
  • General

Cite this

Haraguchi, S., Day, N. K., Nelson, R., Emmanuel, P., Duplantier, J. E., Christodoulou, C. S., & Good, R. A. (1998). Interleukin 12 deficiency associated with recurrent infections. Proceedings of the National Academy of Sciences of the United States of America, 95(22), 13125-13129. https://doi.org/10.1073/pnas.95.22.13125

Interleukin 12 deficiency associated with recurrent infections. / Haraguchi, Soichi; Day, Noorbibi K.; Nelson, Robert; Emmanuel, Patricia; Duplantier, John E.; Christodoulou, Christodoulos S.; Good, Robert A.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 95, No. 22, 27.10.1998, p. 13125-13129.

Research output: Contribution to journalArticle

Haraguchi, Soichi ; Day, Noorbibi K. ; Nelson, Robert ; Emmanuel, Patricia ; Duplantier, John E. ; Christodoulou, Christodoulos S. ; Good, Robert A. / Interleukin 12 deficiency associated with recurrent infections. In: Proceedings of the National Academy of Sciences of the United States of America. 1998 ; Vol. 95, No. 22. pp. 13125-13129.
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