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Abstract
Tuberculosis (TB) caused by Mycobacterium tuberculosis (Mtb) is a global health problem. At present, prior exposure to Mtb can be determined by blood-based interferon-gamma release assay (IGRA), but active TB is not always detectable by blood tests such as CRP and ESR. This study was undertaken to investigate whether leucine-rich alpha-2 glycoprotein (LRG), a new inflammatory biomarker, could be used to assess active disease of TB. Cynomolgus macaques pretreated with or without Bacille Calmette-Guerin (BCG) vaccination were inoculated with Mtb to induce active TB. Blood was collected over time from these animals and levels of LRG as well as CRP and ESR were quantified. In the macaques without BCG vaccination, Mtb inoculation caused extensive TB and significantly increased plasma CRP and LRG levels, but not ESR. In the macaques with BCG vaccination, whereas Mtb challenge caused pulmonary TB, only LRG levels were significantly elevated. By immunohistochemical analysis of the lung, LRG was visualized in epithelioid cells and giant cells of the granulation tissue. In humans, serum LRG levels in TB patients were significantly higher than those in healthy controls and declined one month after anti-tubercular therapy. These findings suggest that LRG is a promising biomarker when performed following IGRA for the detection of active TB.
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Details
1 Department of Clinical Immunology, Kochi Medical School, Kochi University, Nankoku, Japan
2 Department of Medicine, Osaka Prefectural Hospital Organization Osaka Habikino Medical Center, Habikino, Japan; Department of Internal Medicine, Osaka Anti-Tuberculosis Association Osaka Hospital, Neyagawa, Japan (GRID:grid.460257.2)
3 Department of Clinical Immunology, Kochi Medical School, Kochi University, Nankoku, Japan (GRID:grid.460257.2)
4 Laboratory of Immunoregulation and Vaccine Research, Tsukuba Primate Research Center, National Institutes of Biomedical Innovation, Health and Nutrition, Tsukuba, Japan (GRID:grid.482562.f)
5 Department of Clinical Research Center, Osaka Prefectural Hospital Organization Osaka Habikino Medical Center, Habikino, Japan (GRID:grid.482562.f)
6 Department of Clinical Immunology, Kochi Medical School, Kochi University, Nankoku, Japan (GRID:grid.482562.f); Laboratory of Immune Signal, National Institutes of Biomedical Innovation, Health and Nutrition, Ibaraki, Japan (GRID:grid.482562.f)