Zhengwei Dong1, Jingyun Shi2, Anca Dorhoi3, Jie Zhang4, Adiilah K Soodeen-Lalloo5, WenLing Tan6, Hongyun Yin7, Wei Sha7, Weitong Li8, Ruijuan Zheng6, Zhonghua Liu6, Hua Yang6, Lianhua Qin6, Jie Wang6, Xiaochen Huang6, Chunyan Wu1, Stefan H E Kaufmann3, Yonghong Feng9. 1. Shanghai Key Lab of Tuberculosis, Shanghai Pulmonary Hospital, Tongji University, School of Medicine, Shanghai, China; Department of Pathology, Shanghai Pulmonary Hospital, Tongji University, School of Medicine, Shanghai, China. 2. Shanghai Key Lab of Tuberculosis, Shanghai Pulmonary Hospital, Tongji University, School of Medicine, Shanghai, China; Department of Radiology, Shanghai Pulmonary Hospital, Tongji University, School of Medicine, Shanghai, China. 3. Department of Immunology, Max Planck Institute for Infection Biology, Berlin, Germany. 4. Department of Epidemiology and Biostatistics, Tongji University, School of Medicine, Shanghai, China. 5. Department of Radiology, Shanghai Pulmonary Hospital, Tongji University, School of Medicine, Shanghai, China. 6. Shanghai Key Lab of Tuberculosis, Shanghai Pulmonary Hospital, Tongji University, School of Medicine, Shanghai, China. 7. Clinic and Research Center of Tuberculosis, Shanghai Pulmonary Hospital, Tongji University, School of Medicine, Shanghai, China. 8. Department of Radiology, Shishi Hospital, Fujian, China. 9. Shanghai Key Lab of Tuberculosis, Shanghai Pulmonary Hospital, Tongji University, School of Medicine, Shanghai, China; Clinic and Research Center of Tuberculosis, Shanghai Pulmonary Hospital, Tongji University, School of Medicine, Shanghai, China. Electronic address: feng_yonghong@hotmail.com.
Abstract
BACKGROUND: Exacerbated immunopathology is a frequent consequence of TB that is complicated by diabetes mellitus (DM); however, the underlying mechanisms are still poorly defined. METHODS: In the two groups of age- and sex-matched patients with TB and DM (DM-TB) and with TB and without DM, we microscopically evaluated the areas of caseous necrosis and graded the extent of perinecrotic fibrosis in lung biopsies from the sputum smear-negative (SN) patients. We scored acid-fast bacilli in sputum smear-positive (SP) patients and compiled CT scan data from both the SN and SP patients. We compared inflammatory biomarkers and routine hematologic and biochemical parameters. Binary logistic regression analyses were applied to define the indices associated with the extent of lung injury. RESULTS: Enlarged caseous necrotic areas with exacerbated fibrotic encapsulations were found in SN patients with DM-TB, consistent with the higher ratio of thick-walled cavities and more bacilli in the sputum from SP patients with DM-TB. Larger necrotic foci were detected in men compared with women within the SN TB groups. Significantly higher fibrinogen and lower high-density lipoprotein cholesterol (HDL-C) were observed in SN patients with DM-TB. Regression analyses revealed that diabetes, activation of the coagulation pathway (shown by increased platelet distribution width, decreased mean platelet volume, and shortened prothrombin time), and dyslipidemia (shown by decreased low-density lipoprotein cholesterol, HDL-C, and apolipoprotein A) are risk factors for severe lung lesions in both SN and SP patients with TB. CONCLUSIONS: Hemostasis and dyslipidemia are associated with granuloma necrosis and fibroplasia leading to exacerbated lung damage in TB, especially in patients with DM-TB.
BACKGROUND: Exacerbated immunopathology is a frequent consequence of TB that is complicated by diabetes mellitus (DM); however, the underlying mechanisms are still poorly defined. METHODS: In the two groups of age- and sex-matched patients with TB and DM (DM-TB) and with TB and without DM, we microscopically evaluated the areas of caseous necrosis and graded the extent of perinecrotic fibrosis in lung biopsies from the sputum smear-negative (SN) patients. We scored acid-fast bacilli in sputum smear-positive (SP) patients and compiled CT scan data from both the SN and SP patients. We compared inflammatory biomarkers and routine hematologic and biochemical parameters. Binary logistic regression analyses were applied to define the indices associated with the extent of lung injury. RESULTS: Enlarged caseous necrotic areas with exacerbated fibrotic encapsulations were found in SN patients with DM-TB, consistent with the higher ratio of thick-walled cavities and more bacilli in the sputum from SP patients with DM-TB. Larger necrotic foci were detected in men compared with women within the SN TB groups. Significantly higher fibrinogen and lower high-density lipoprotein cholesterol (HDL-C) were observed in SN patients with DM-TB. Regression analyses revealed that diabetes, activation of the coagulation pathway (shown by increased platelet distribution width, decreased mean platelet volume, and shortened prothrombin time), and dyslipidemia (shown by decreased low-density lipoprotein cholesterol, HDL-C, and apolipoprotein A) are risk factors for severe lung lesions in both SN and SP patients with TB. CONCLUSIONS:Hemostasis and dyslipidemia are associated with granuloma necrosis and fibroplasia leading to exacerbated lung damage in TB, especially in patients with DM-TB.
Authors: Elinor Hortle; Khelsey E Johnson; Matt D Johansen; Tuong Nguyen; Jordan A Shavit; Warwick J Britton; David M Tobin; Stefan H Oehlers Journal: J Infect Dis Date: 2019-07-02 Impact factor: 5.226
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Authors: Stacey Bartlett; Adrian Tandhyka Gemiarto; Minh Dao Ngo; Haressh Sajiir; Semira Hailu; Roma Sinha; Cheng Xiang Foo; Léanie Kleynhans; Happy Tshivhula; Tariq Webber; Helle Bielefeldt-Ohmann; Nicholas P West; Andriette M Hiemstra; Candice E MacDonald; Liv von Voss Christensen; Larry S Schlesinger; Gerhard Walzl; Mette Marie Rosenkilde; Thomas Mandrup-Poulsen; Katharina Ronacher Journal: Front Immunol Date: 2020-11-06 Impact factor: 8.786