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Original Research: Chest Infections |

Heightened Plasma Levels of Heme Oxygenase-1 and Tissue Inhibitor of Metalloproteinase-4 as Well as Elevated Peripheral Neutrophil Counts Are Associated With TB-Diabetes ComorbidityMarkers of Pathogenesis in TB-Diabetes

Bruno B. Andrade, MD, PhD; Nathella Pavan Kumar, MS; Rathinam Sridhar, MD; Vaithilingam V. Banurekha, MBBS; Mohideen S. Jawahar, MD; Thomas B. Nutman, MD; Alan Sher, PhD; Subash Babu, MBBS, PhD
Author and Funding Information

From the Immunobiology Section (Drs Andrade and Sher), and the Helminth Immunology Section (Drs Nutman and Babu), Laboratory of Parasitic Diseases, National Institutes of Health, Bethesda, MD; the National Institutes of Health (Mr Pavan Kumar and Dr Babu), International Center for Excellence in Research, Chennai, India; the National Institute for Research in Tuberculosis (Mr Pavan Kumar and Drs Banurekha and Jawahar), Chennai, India; and the Government Stanley Medical Hospital (Dr Sridhar), Chennai, India.

Correspondence to: Bruno B. Andrade, MD, PhD, Laboratory of Parasitic Diseases, National Institutes of Health, 50 S Dr, Room 6146, Bethesda, MD 20892-8003; e-mail: andradebd@niaid.nih.gov


Dr Andrade and Mr Pavan Kumar contributed equally to the work.

Funding/Support: This work was supported by the Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health.

Reproduction of this article is prohibited without written permission from the American College of Chest Physicians. See online for more details.


Chest. 2014;145(6):1244-1254. doi:10.1378/chest.13-1799
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Background:  The increased prevalence of type 2 diabetes mellitus (T2DM) in countries endemic for TB poses a serious complication in the clinical management of this major infectious disease. Understanding the impact of T2DM on TB and the determinants of comorbidity is critical in responding to this growing public health problem with better therapeutic approaches. Here, we performed an exploratory study assessing a series of biologic parameters that could serve as markers of pathogenesis in TB with T2DM.

Methods:  Cross-sectional analyses of levels of heme oxygenase-1 (HO-1), acute phase proteins, tissue metalloproteinases, and tissue inhibitors of metalloproteinase (TIMPs) as well as cytokines and chemokines were performed in plasma samples from individuals with active pulmonary TB or with coincident TB and T2DM from South India.

Results:  Compared with patients with TB without diabetes, those with coincident T2DM exhibited increased Mycobacterium tuberculosis bacillary loads in sputum. Plasma levels of HO-1 but not of other acute phase proteins were higher in patients with TB and T2DM than in patients without diabetes, independent of bacillary sputum loads. HO-1 concentrations also positively correlated with random plasma glucose, circulating glycosylated hemoglobin, and low-density lipoprotein levels. Moreover, patients with coincident TB and T2DM exhibited increased plasma levels of TIMP-4 and elevated peripheral blood neutrophil counts, which, when considered together with HO-1, resulted in increased power to discriminate individuals with active TB with and without T2DM.

Conclusions:  Elevated plasma levels of HO-1 and TIMP-4 and peripheral blood neutrophil counts are potential single and combined markers of pathogenesis in TB and T2DM.

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