IngentaConnect Analysis of the interleukin-12/interferon- pathway in children wi...

Authors: Serour, Francis; Mizrahi, Avraham; Somekh, Eli; Feinberg, Jacqueline; Picard, Capucine; Casanova, Jean-Laurent; Dalal, Ilan¹

Source: European Journal of Pediatrics, Volume 166, Number 8, August 2007 , pp. 835-841(7)

Publisher: Springer

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.

Keywords: Non-tuberculous Mycobacterium; Cervical lymphadenitis; Children; Interleukin-12; Interferon-γ

Document Type: Research article

DOI: 10.1007/s00431-006-0338-2

Affiliations: 1: Email: dalal@wolfson.health.gov.il

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