Analysis of the interleukin-12/interferon-gamma pathway in children with non-tuberculous mycobacterial cervical lymphadenitis.
Genetic defects along the interleukin (IL)-12/interferon (IFN)-gamma 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-gamma 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-gamma and levels of IL-12p40 and IFN-gamma 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-gamma 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-gamma axis might be associated with an isolated cervical lymph node infection and not a disseminated disease in children.
Serour
Francis
F
Department of Pediatric Surgery, The E. Wolfson Medical Center, Holon, Israel.
Mizrahi
Avraham
A
Somekh
Eli
E
Feinberg
Jacqueline
J
Picard
Capucine
C
Casanova
Jean-Laurent
JL
Dalal
Ilan
I
D002648:Child; D002675:Child, Preschool; D005260:Female; D006801:Humans; D007223:Infant; D007371:Interferon-gamma / Q000378:metabolism*; D018664:Interleukin-12 / Q000378:metabolism*; D053762:Interleukin-12 Subunit p40 / Q000378:metabolism*; D008297:Male; D009161:Mycobacterium / Q000302:isolation & purification; D009165:Mycobacterium Infections, Nontuberculous / Q000276:immunology*; D009163:Mycobacterium bovis / Q000276:immunology; D012189:Retrospective Studies; D014374:Tuberculin Test; D014388:Tuberculosis, Lymph Node / Q000276:immunology* / Q000382:microbiology
D053762:Interleukin-12 Subunit p40; D018664:Interleukin-12; D007371:Interferon-gamma