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Interleukin 12 deficiency associated with recurrent infections
S Haraguchi1, N K Day, R P Nelson
1Department of Pediatrics, University of South Florida College of Medicine/All Children's Hospital, 801 Sixth Street South, St. Petersburg, FL 33701, USA.
Summary
A child with interleukin 12 (IL-12) deficiency experienced recurrent infections without fever. This immune disorder stemmed from a lack of IL-12 production, impacting cellular signaling pathways.
Area of Science:
- Immunology
- Genetics
Background:
- Interleukin 12 (IL-12) is crucial for cell-mediated immunity and defense against intracellular pathogens.
- IL-12 deficiency can lead to severe, recurrent infections, often presenting atypically without fever.
Observation:
- A 3-year-old female presented with recurrent pneumococcal pneumonia and sepsis, notably without fever.
- Her peripheral blood mononuclear cells (PBMCs) showed normal responses to antigens and normal antibody production.
- Crucially, stimulated PBMCs failed to produce detectable IL-12 p70 heterodimer, with reduced interferon gamma (IFN-gamma) levels.
Findings:
- The patient's PBMCs lacked IL-12 p70 production upon stimulation, indicating a deficiency in this key cytokine.
- Reverse transcription-PCR confirmed undetectable IL-12 p40 subunit mRNA, suggesting a defect in gene expression or the gene itself.
- While other cytokines like IL-2, IL-6, and TNF-alpha were produced, the IL-12 pathway was specifically impaired.
Implications:
- This case highlights a potential defect in the signaling pathways regulating IL-12 p40 gene expression or an abnormality within the IL-12 p40 gene.
- Understanding this deficiency provides insights into the complex regulation of IL-12 production and its role in host defense.
- Further investigation is warranted to pinpoint the exact genetic or signaling defect, aiding in diagnosis and potential therapeutic strategies for similar immune disorders.