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Analysis of the interleukin-12/interferon-γ pathway in children with non-tuberculous mycobacterial cervical lymphadenitis

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Abstract

Genetic defects along the interleukin (IL)-12/interferon (IFN)−γ pathway have been found in patients with mendelian susceptibility to mycobacterial disease (MSMD) caused by live BCG vaccine or non-tuberculous Mycobacterium (NTM) species, highlighting the crucial role of this axis in human immunity to Mycobacterium. The aims of this study were to characterize healthy children presenting with cervical lymphadenitis caused by NTM and to investigate their IL-12/IFN-γ pathway. Epidemiological, clinical, laboratory and pathological findings were reviewed retrospectively. Blood samples from five patients and healthy controls were in vitro activated with BCG, BCG + IL-12 and BCG + IFN-γ and levels of IL-12p40 and IFN-γ were measured. Fourteen patients (11 males, median age 24 months, range 12–78 months) were studied. The mean duration of illness before diagnosis was 9.1 weeks. Mycobacterium tuberculosis purified protein derivate (PPD) was positive in all patients (mean 14.5 ± 9.8 mm). Caseous granuloma was found in all ten patients who underwent excision biopsy. However, acid fast stain was positive in only five children and cultures were positive in only three cases. The amplified M. tuberculosis direct test was negative in all tested cases. No significant differences in IL-12p40 and IFN-γ levels were found between patients and controls. In spite of the normal response as measured in the screening test, it is still possible that patients might have a monogenic/mendelian disease for which the genetic defect(s) have yet to be elucidated. Alternatively, some single nucleotide polymorphisms along the IL-12/IFN-γ axis might be associated with an isolated cervical lymph node infection and not a disseminated disease in children.

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Abbreviations

NTM:

Nontuberculous Mycobacterium species

BCG:

Bacillus Calmette-Guérin

HIV:

Human immunodeficiency virus

MSMD:

mendelian susceptibility to mycobacterial disease

IL:

interleukin

IFN:

interferon

STAT:

signal transducer and activator of transcription

TB:

tuberculosis

PPD:

purified protein derivate

AMTD:

amplified Mycobacterium tuberculosis direct test

RNA:

Ribonucleic acid

FNA:

fine needle aspiration

NK cells:

natural killer cells

IL-12R:

interleukin-12 receptor

IFN-γR:

interferon−γ receptor

TNF:

tumor necrosis factor

NRAMP-1:

natural resistance associated macrophage protein

TLR:

Toll-like receptor

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Authors and Affiliations

  1. Department of Pediatric Surgery, The E. Wolfson Medical Center, Holon, Israel

    Francis Serour

  2. Department of Pediatrics, The E. Wolfson Medical Center, Holon, Israel

    Avraham Mizrahi

  3. Pediatric Infectious/Allergy/Immunology Unit, The E. Wolfson Medical Center, Halokhamim Street 62, P.O. Box 5, Holon, 58100, Israel

    Eli Somekh & Ilan Dalal

  4. Laboratoire de Génétique Humaine des Maladies Infectieuses, Université de Paris René Descartes INSERM U550, Faculté de Médecine Necker, Paris, France

    Jacqueline Feinberg, Capucine Picard & Jean-Laurent Casanova

  5. Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel

    Francis Serour, Eli Somekh & Ilan Dalal

  6. Unité d’Immunologie et d’Hématologie pédiatriques, Hôpital Necker-Enfants Malades, Paris, France

    Jean-Laurent Casanova

Authors
  1. Francis Serour
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  2. Avraham Mizrahi
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  3. Eli Somekh
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  4. Jacqueline Feinberg
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  5. Capucine Picard
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  6. Jean-Laurent Casanova
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  7. Ilan Dalal
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Correspondence to Ilan Dalal.

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Serour, F., Mizrahi, A., Somekh, E. et al. Analysis of the interleukin-12/interferon-γ pathway in children with non-tuberculous mycobacterial cervical lymphadenitis. Eur J Pediatr 166, 835–841 (2007). https://doi.org/10.1007/s00431-006-0338-2

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  • DOI: https://doi.org/10.1007/s00431-006-0338-2

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