TNF-α/IL-2 ratio discriminates latent from active tuberculosis in immunocompetent children: a pilot study.
BACKGROUND
Distinguishing latent tuberculosis (LTB) from tuberculosis (TB) disease may be challenging in children. Here, we analyzed cytokine profiles that can distinguish the two infection stages in a nonendemic country (France).


METHODS
Immunocompetent children with LTB (n = 6) or TB disease (n = 8) (median age: 6.2 and 5.7 years, respectively) were analyzed. Four young uninfected children were included as controls. A Luminex assay evaluated cytokine responses to Mycobacterium tuberculosis antigens.


RESULTS
Poor interleukin-4 (IL-4) and IL-10 responses precluded analysis of these cytokines. Interferon-γ (IFN-γ), tumor necrosis factor-α (TNF-α), IL-2, and T-helper type 1 (Th1) cytokines and IL-5, IL-13, T-helper type 2 (Th2) cytokines were simultaneously induced by antigens in 14/14 infected but 0/4 uninfected children. Th1 cytokine levels were similar in LTB and TB disease: IFN-γ: 12,254 and 10,495 pg/ml; IL-2: 2,097 and 1,869 pg/ml; and TNF-α: 1,020 and 2,875 pg/ml, respectively. Th2 cytokine levels were similar and even higher in LTB than in TB disease: IL-5: 23 and 10 pg/ml; IL-13: 284 and 109 pg/ml, respectively. Positive correlation of cytokine levels, whether Th1 or Th2, was observed. Higher (P = 0.008) TNF-α/IL-2 ratios distinguished 6/8 active TB disease cases from 6/6 LTB cases.


CONCLUSIONS
TNF-α/IL-2 ratio may discriminate TB disease from LTB in immunocompetent children. Larger studies in TB endemic settings must verify these results.
Laboratory of Immunology, Robert Debré Hospital, AP-HP-Faculty of Medicine, Paris 7 Denis Diderot University, Paris, France. ghislaine.sterkers@rdb.aphp.fr
Nadège
N
Gourgouillon
Agathe
A
de Lauzanne
Charles-Henry
CH
Cottart
Emmanuel
E
Curis
Camille
C
Debord
Valérie
V
Guérin-El Khourouj
Béatrice
B
Pédron
Albert
A
Faye
Ghislaine
G
Sterkers
D000293:Adolescent; D015415:Biomarkers / Q000097:blood; D002648:Child; D002675:Child, Preschool; D003937:Diagnosis, Differential; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D007121:Immunocompetence; D007159:Immunologic Tests; D007223:Infant; D059425:Interferon-gamma Release Tests; D007376:Interleukin-2 / Q000097:blood*; D055985:Latent Tuberculosis / Q000097:blood / Q000175:diagnosis* / Q000276:immunology; D008297:Male; D009169:Mycobacterium tuberculosis / Q000276:immunology* / Q000302:isolation & purification; D010865:Pilot Projects; D011237:Predictive Value of Tests; D011446:Prospective Studies; D013183:Sputum / Q000382:microbiology; D014374:Tuberculin Test; D014376:Tuberculosis / Q000097:blood / Q000175:diagnosis* / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000097:blood*
D015415:Biomarkers; C508594:IL2 protein, human; D007376:Interleukin-2; D014409:Tumor Necrosis Factor-alpha