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

Abstract

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. 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 (VEGF-receptor 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. 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. 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.