Mannose-binding protein B allele confers protection against tuberculous meningitis

被引:140
作者
Hoal-van Helden, EG
Epstein, J
Victor, TC
Hon, DN
Lewis, LA
Beyers, N
Zurakowski, D
Ezekowitz, RAB
van Helden, PD
机构
[1] Univ Stellenbosch, MRC, Ctr Mol & Cellular Biol, Dept Biochem Med, ZA-7505 Tygerberg, South Africa
[2] Univ Stellenbosch, Sch Med, Dept Pediat, ZA-7505 Tygerberg, South Africa
[3] Harvard Univ, Sch Med, Boston, MA 02114 USA
[4] Childrens Hosp, Dept Pediat, Boston, MA 02114 USA
[5] Massachusetts Gen Hosp, Lab Dev Immunol, Boston, MA 02114 USA
关键词
D O I
10.1203/00006450-199904010-00002
中图分类号
R72 [儿科学];
学科分类号
100202 ;
摘要
Inhalation is the principal mode of entry for Mycobacterium tuberculosis in humans. Primary infection is usually restricted to the lungs and contiguous lymph nodes. In a subset of infected individuals, predominantly children, the infection is spread hematogenously to the meninges. The host factors that influence the development of tuberculous meningitis have not been well elucidated. The mannose-binding protein (MBP), a serum protein, is considered as an "ante-antibody." MBP has been shown to bind mycobacteria and acts as an opsonin in vitro. Although MBP plays a role in first-line host defense, it may under certain circumstances be deleterious to the host. In tuberculosis (TB), MBP may assist the spread of this intracellular pathogen. Therefore, we hypothesized that MBP genotypes that result in a phenotype of low MBP levels might be protective. We studied a well-defined South African population in which TB has reached epidemic levels. We found that the MBP B allele (G54D), which disrupts the collagen region of the protein and results in low MBP levels, was found in 22 of 79 (28%) of the TB-negative controls from the same community, compared with 12 of 91 (13%) of the patients with pulmonary TB (p < 0.017), and 5 of 64 (8%) of patients with tuberculous meningitis (p < 0.002). In addition, we found significantly lower serum MBP concentrations in TB-negative controls compared with postacute phase, fully recovered TB patients (p < 0.004). These findings suggest that the MBP B allele affords protection against tuberculous meningitis.
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页码:459 / 464
页数:6
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