Tuberculous lymphadenitis is associated with altered levels of circulating angiogenic factors.

Gokul Raj, K.; Moideen, K.; Baskaran, D.; Sekar, G.; Rathinam, S.; Bharathi, V.J.; Ganeshan, G.R.; Babu, S.

International Journal of Tuberculosis and Lung Disease; 2018; 22(5): 557–566.

Summary: Background: Angiogenic factors are important in granuloma formation and serve as biomarkers in pulmonary tuberculosis (PTB). The relationship between these markers and tuberculous lymphadenitis (TBL) is not known.

Objective and Design: To examine the association of vascular endothelial growth factor (VEGF) and angiopoietin (Ang) family molecules in TBL, we measured systemic levels of VEGF-A, C, D, R1 (VEGFreceptor 1), R2, R3, Ang-1, Ang-2 and TIE2 (tyrosine kinase with immunoglobulin-like and epidermal growth factor-like domains 2) levels in TBL, latent tuberculous infection (LTBI) and lymph node culture supernatants (VEGF-A, C and Ang-2) of the same TBL patients.

Results: Circulating levels of VEGF-A and VEGF-C were significantly diminished, whereas VEGF-R2, R3, Ang-2 and TIE2 levels were significantly increased, in TBL. Likewise, VEGF-A, C and Ang-2 levels were significantly increased in lymph node supernatants compared with plasma in individuals with TBL. Receiver operating characteristic curve analysis showed that VEGF-C and VEGF-R2 markers clearly distinguished TBL from LTBI. Following treatment, VEGF-C and Ang-1 levels were significantly altered. No association was observed between angiogenic factors and culture grade or lymph node size, except for VEGF-A. VEGF-A was also significantly decreased in multiple lymph nodes compared with single lymph nodes.

Conclusions: Our data suggest that altered levels of circulating angiogenic factors in TBL might reflect underlying vasculo-endothelial dysfunction. Reversal of angiogenic markers after anti-tuberculosis treatment suggests that these angiogenic markers may serve as biomarkers of disease severity or response to treatment in TBL.

Keywords: Tuberculous lymphadenitis; ELISA; VEGF; Angiopoietin; Circulating biomarker

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