Yun-Gyoung Hur1, Wou Young Chung2, Ahreum Kim1, Young Sun Kim2, Hyon-Suk Kim3, Sun-Hee Jang1, Yeun Kim4, Hyeyoung Lee4, Kwang Joo Park5, Sang-Nae Cho6. 1. Department of Microbiology and Institute for Immunology and Immunological Diseases, Brain Korea 21 Plus Project for Medical Science, Yonsei University College of Medicine, Seoul 03722, Republic of Korea. 2. Department of Pulmonary and Critical Care Medicine, Ajou University School of Medicine, San 5, Wonchon-dong, Yeongtong-gu, Suwon 16499, Gyeonggi, Republic of Korea. 3. Department of Laboratory Medicine, Severance Hospital, Yonsei University College of Medicine, Seoul 03722, Republic of Korea. 4. Department of Biomedical Laboratory Science, College of Health Sciences, Yonsei University, Wonju 26493, Gangwon, Republic of Korea. 5. Department of Pulmonary and Critical Care Medicine, Ajou University School of Medicine, San 5, Wonchon-dong, Yeongtong-gu, Suwon 16499, Gyeonggi, Republic of Korea. Electronic address: parkkj@ajou.ac.kr. 6. Department of Microbiology and Institute for Immunology and Immunological Diseases, Brain Korea 21 Plus Project for Medical Science, Yonsei University College of Medicine, Seoul 03722, Republic of Korea. Electronic address: raycho@yuhs.ac.
Abstract
OBJECTIVES: Beijing strain of Mycobacterium tuberculosis (M. tb) is characterized by a high incidence of transmission, relapse, and drug resistance. This study aimed to determine host immune responses to antigens derived from the Beijing/K strain which has been highly prevalent in tuberculosis (TB) outbreaks in South Korea. METHODS: We recruited 52 TB patients and 96 healthy subjects comprising 31 individuals with latent TB infection (LTBI) and 65 TB-naïve controls based on QuantiFERON-TB Gold In-Tube (QFT-IT) tests. Blood samples were obtained for diluted whole-blood assays, multiplex bead arrays, ELISpot assays, and HLA typing. Molecular genotyping of M. tb was performed using clinical isolates. RESULTS: Active TB and LTBI groups were differentiated by TNF-α concentrations induced by the Beijing/K strain-derived antigens, MTBK_24790 and MTBK_24800 (P < 0.001). MTBK_24800-induced IFN-γ and CXCL10 concentrations discriminated the TB-infected groups from TB-naïve controls (P < 0.001). IFN-γ-producing T cells were generated in 87.2% of TB patients in response to MTBK_24800 peptide antigens. The major immunogenic epitope was at C-terminal of the antigen, and predominantly recognized by HLA-DR4 and -DQ4. CONCLUSIONS: Measurement of IFN-γ, CXCL10, and TNF-α concentrations induced by MTBK_24790 and MTBK_24800 may contribute to improved diagnosis of TB and vaccine development in regions where the Beijing/K strain is endemic.
OBJECTIVES: Beijing strain of Mycobacterium tuberculosis (M. tb) is characterized by a high incidence of transmission, relapse, and drug resistance. This study aimed to determine host immune responses to antigens derived from the Beijing/K strain which has been highly prevalent in tuberculosis (TB) outbreaks in South Korea. METHODS: We recruited 52 TB patients and 96 healthy subjects comprising 31 individuals with latent TB infection (LTBI) and 65 TB-naïve controls based on QuantiFERON-TB Gold In-Tube (QFT-IT) tests. Blood samples were obtained for diluted whole-blood assays, multiplex bead arrays, ELISpot assays, and HLA typing. Molecular genotyping of M. tb was performed using clinical isolates. RESULTS: Active TB and LTBI groups were differentiated by TNF-α concentrations induced by the Beijing/K strain-derived antigens, MTBK_24790 and MTBK_24800 (P < 0.001). MTBK_24800-induced IFN-γ and CXCL10 concentrations discriminated the TB-infected groups from TB-naïve controls (P < 0.001). IFN-γ-producing T cells were generated in 87.2% of TB patients in response to MTBK_24800 peptide antigens. The major immunogenic epitope was at C-terminal of the antigen, and predominantly recognized by HLA-DR4 and -DQ4. CONCLUSIONS: Measurement of IFN-γ, CXCL10, and TNF-α concentrations induced by MTBK_24790 and MTBK_24800 may contribute to improved diagnosis of TB and vaccine development in regions where the Beijing/K strain is endemic.
Authors: Ji Young Hong; Ahreum Kim; So Yeong Park; Sang-Nae Cho; Hazel M Dockrell; Yun-Gyoung Hur Journal: Front Cell Infect Microbiol Date: 2021-03-18 Impact factor: 5.293