Immune function in young children with previous pulmonary or miliary/meningeal tuberculosis and impact of BCG vaccination.
Abstract | OBJECTIVE: PATIENTS AND METHODS: We conducted a case-control study among HIV-seronegative Brazilian children who were <5 years old. Case subjects had previous culture-confirmed or clinical miliary/ meningeal tuberculosis. There were 2 sets of control subjects: those with culture-confirmed pulmonary tuberculosis and purified protein derivative-positive household contacts. All of the children had completed treatment. Peripheral blood mononuclear cells were stimulated ( phytohemagglutinin, phytohemagglutinin + interleukin 12, lipopolysaccharide, lipopolysaccharide + interferon-gamma, and purified protein derivative), and cytokine responses ( interleukin 1beta, interleukin-4, interleukin-6, interleukin-8, interleukin 10, interleukin 12, interferon-gamma, tumor necrosis factor-alpha, and monocyte chemoattractant protein 1) were quantified by bead-based assay. Median cytokine responses were compared by the Kruskal-Wallis test. Multivariate analysis of variance accounted for multiple comparisons. RESULTS: There were 18 case subjects with miliary/ meningeal tuberculosis, 28 pulmonary control subjects, and 29 purified protein derivative-positive control subjects. The median age was 4.2 years. There was no difference in case and control subjects by age, gender, race, BMI, or median CD4 count. Twelve (67%) of 18 case subjects, 26 (93%) of 28 pulmonary control subjects, and 28 (97%) of 29 purified protein derivative-positive subjects had received BCG vaccine. No cytokine defects were identified in case subjects with miliary/ meningeal tuberculosis compared with either set of control subjects. Pulmonary control subjects had uniformly higher monocyte chemoattractant protein 1 levels than case subjects with miliary/ meningeal tuberculosis and purified protein derivative-positive control subjects, both at rest and with lipopolysaccharide, lipopolysaccharide + interferon-gamma, and purified protein derivative stimulation. Pulmonary control subjects did not have a higher frequency of allele G in the -2518 monocyte chemoattractant protein 1 promoter polymorphism. Case subjects with miliary/ meningeal tuberculosis who had received BCG vaccine (n = 12) had lower stimulated interleukin 8 production than children who did not receive BCG vaccine (n = 6). CONCLUSIONS:
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Authors | Timothy R Sterling, Terezinha Martire, Alexandre Silva de Almeida, Li Ding, David E Greenberg, Lorena Alves Moreira, Houda Elloumi, Angelica P V Torres, Clemax Couto Sant'Anna, Eliane Calazans, Geraldo Paraguassu, Tebeb Gebretsadik, Ayumi Shintani, Kathleen Miller, Afranio Kritski, Jose Roberto Lapa e Silva, Steven M Holland |
Journal | Pediatrics
(Pediatrics)
Vol. 120
Issue 4
Pg. e912-21
(Oct 2007)
ISSN: 1098-4275 [Electronic] United States |
PMID | 17908747
(Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, N.I.H., Intramural)
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Chemical References |
- BCG Vaccine
- Chemokine CCL2
- Interleukin-8
- Lipopolysaccharides
- Phytohemagglutinins
- Tuberculin
- Interferon-gamma
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Topics |
- BCG Vaccine
- Brazil
- Case-Control Studies
- Chemokine CCL2
(blood, genetics)
- Child
- Child, Preschool
- Female
- Gene Frequency
- Genotype
- Humans
- Interferon-gamma
(pharmacology)
- Interleukin-8
(blood)
- Lipopolysaccharides
- Lymphocyte Activation
- Male
- Phytohemagglutinins
(pharmacology)
- T-Lymphocytes
(immunology)
- Tuberculin
(pharmacology)
- Tuberculosis, Meningeal
(immunology)
- Tuberculosis, Pulmonary
(immunology)
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