Angiopoietins as biomarkers of disease severity and bacterial burden in pulmonary tuberculosis.
Circulating angiogenic factors of the vascular endothelial growth factor family are important biomarkers of disease severity in pulmonary tuberculosis (PTB). However, the role of angiopoietins, which are also involved in angiogenesis, in PTB is not known.



To examine the association of circulating angiopoietins with TB disease or latent tuberculous infection (LTBI), we examined the systemic levels of angiopoietin (Ang) 1, Ang 2 and Tie-2 receptor in individuals with PTB (n = 44), LTBI (n = 44) or no tuberculous infection (NTBI) (n = 44).



Circulating levels of Ang-1, Ang-2 and Tie-2 were significantly higher in PTB than in individuals with LTBI or NTBI. Moreover, Ang-1, Ang-2 and Tie-2 levels were significantly higher in PTB with bilateral disease. The levels of these factors also exhibited a significant positive relationship with bacterial burdens in PTB. Receiver operating characteristics curve analysis revealed Ang-2 as a marker distinguishing PTB from LTBI or NTBI. Finally, the circulating levels of Ang-1, Ang-2 and Tie-2 were significantly reduced following anti-tuberculosis chemotherapy.



Our data demonstrate that PTB is associated with elevated levels of circulating angiopoietins, possibly reflecting endothelial dysfunction. In addition, Ang-2 could prove useful as a biomarker to monitor disease severity, bacterial burden and therapeutic responses.
International Center for Excellence in Research, National Institutes of Health, Chennai, India.
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Kumar
National Institutes for Research in Tuberculosis, Chennai, India.
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Velayutham
National Institutes for Research in Tuberculosis, Chennai, India.
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Nair
International Center for Excellence in Research, National Institutes of Health, Chennai, India; Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA.
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Babu
D000293:Adolescent; D000328:Adult; D042682:Angiopoietins / Q000097:blood*; D000995:Antitubercular Agents / Q000627:therapeutic use; D015415:Biomarkers / Q000097:blood*; D016022:Case-Control Studies; D005260:Female; D006801:Humans; D055985:Latent Tuberculosis / Q000097:blood / Q000175:diagnosis / Q000188:drug therapy; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D042787:Receptor, TIE-2 / Q000097:blood; D014397:Tuberculosis, Pulmonary / Q000097:blood* / Q000175:diagnosis* / Q000188:drug therapy; D042461:Vascular Endothelial Growth Factor A / Q000097:blood; D055815:Young Adult
D042682:Angiopoietins; D000995:Antitubercular Agents; D015415:Biomarkers; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D042787:Receptor, TIE-2