Tuberculosis associated with Mycobacterium tuberculosis Beijing and non-Beijing genotypes: a clinical and immunological comparison

Abstract

Background: The Mycobacterium tuberculosis Beijing genotype is biologically different from other genotypes. We aimed to clinically and immunologically compare human tuberculosis caused by Beijing and non-Beijing strains.

Methods: Pulmonary tuberculosis patients were prospectively enrolled and grouped by their M. tuberculosis genotypes. The clinical features, plasma cytokine levels, and cytokine gene expression levels in peripheral blood mononuclear cells (PBMC) were compared between the patients in Beijing and non-Beijing groups.

Results: Patients in the Beijing group were characterized by significantly lower frequency of fever (odds ratio, 0.12, p = 0.008) and pulmonary cavitation (odds ratio, 0.2, p = 0.049). Night sweats were also significantly less frequent by univariate analysis, and the duration of cough prior to diagnosis was longer in Beijing compared to non-Beijing groups (medians, 60 versus 30 days, p = 0.048). The plasma and gene expression levels of interferon (IFN) gamma and interleukin (IL)-18 were similar in the two groups. However, patients in the non-Beijing group had significantly increased IL-4 gene expression (p = 0.018) and lower IFN-gamma : IL-4 cDNA copy number ratios (p = 0.01).

Conclusion: Patients with tuberculosis caused by Beijing strains appear to be less symptomatic than those who have disease caused by other strains. Th1 immune responses are similar in patients infected with Beijing and non-Beijing strains, but non-Beijing strains activate more Th2 immune responses compared with Beijing strains, as evidenced by increased IL-4 expression.

Figure 1

Cough duration (day) of patients infected with Beijing and non-Beijing strains. Cough durations of the pulmonary tuberculosis patients before diagnosis were compared by Beijing and non-Beijing groups. Patients infected with Beijing strains had significantly longer cough (median, 60 days) compared to those infected with non-Beijing strains (median, 30 days). Two patients in the Beijing group who had 4-year long cough before the diagnosis are expressed as > 300 days. The two groups differed significantly in the duration of cough (p = 0.048).

Figure 2

Plasma cytokine levels. Plasma levels of IFN-γ and IL-18 in pulmonary tuberculosis patients were quantified using ELISA assay. Patients infected with Beijing and non-Beijing strains showed similar levels of IFN-γ (p = 0.994) and IL-18 level (p = 0.341). The bars indicate the log median levels in each group.

Figure 3

Comparison of cDNA copies of cytokine genes. cDNA copies of IFN-γ, IL-2, IL-18, and IL-4 were compared by Beijing and non-Beijing groups. The two groups of patients showed no difference in the expression of IFN-γ, IL-2, and IL-18 genes (p > 0.05). But patients infected with non-Beijing strains had significantly higher expressed cDNA copies of IL-4 than those with Beijing strains (p = 0.018). Log medians of cDNA copies are indicated by bars.

Figure 4

IFN-γ : IL-4 cDNA copy number ratio of pulmonary tuberculosis patients. Patients infected with non-Beijing strains had significantly lower ratios than those infected with Beijing strains (p = 0.01). The bars indicate log median ratios.