Abstract
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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Abbreviations
- BCG:
-
bacillus Calmette-Guérin
- MBP:
-
mannose-binding protein
- TB:
-
tuberculosis
- TBM:
-
meningeal tuberculosis
- CI:
-
confidence interval
- ATS:
-
American Thoracic Society
- CRP:
-
C-reactive protein
- OR:
-
odds ratio
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Acknowledgements
The authors thank D. Pearson for technical assistance, T. Kotze for help with statistical analysis, and P. Samaai, D. Bester, and S. Van Zyl for collecting blood samples.
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Supported in part by Glaxo-Wellcome Action TB international research initiative and The Wellcome Trust (UK). J.E. was supported by funding from the Pediatric Scientist Development Program. R.A.B.E. is supported by NIH grant HL43510.
Laboratory of Developmental Immunology and Department of Pediatrics, Massachusetts General Hospital and Harvard Medical School, Boston, MA, 02114
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Hoal-Van Helden, E., Epstein, J., Victor, T. et al. Mannose-Binding Protein B Allele Confers Protection against Tuberculous Meningitis. Pediatr Res 45, 459–464 (1999). https://doi.org/10.1203/00006450-199904010-00002
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DOI: https://doi.org/10.1203/00006450-199904010-00002
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