Concentration of serum vascular endothelial growth factor D and its correlation with functional and clinical variables in patients with lymphangioleiomyomatosis from a Brazilian reference centre

Background: Serum vascular endothelial growth factor D (VEGF-D) has been proposed as a diagnostic and a prognostic biomarker in patients with lymphangioleiomyomatosis (LAM). Objectives: To compare VEGF-D serum levels between LAM patients and healthy women and to define its correlation with clinical and functional parameters. Methods: A cross-sectional study that included patients with sporadic (86%) and tuberous sclerosis complex associated LAM (14%) followed in a Brazilian reference centre. Results: Seventy-one LAM patients and 10 healthy women paired for age (42 ± 11 vs. 36 ± 10 years, respectively, p=0.1) were enrolled. Serum VEGF-D levels were higher in LAM patients than in health women [862 pg/mL (429-1383 pg/mL) vs. 185 pg/mL (132-258 pg/mL), respectively, p<0.001], and were associated with carbon monoxide diffusion capacity (DLCO) (r=-0.34, p=0.005) and there was a trend of correlation with FEV1 (r=-0.21, p=0.08). There were 40 patients (56%) with serum VEGF-D levels >800pg/mL and such subgroup had a higher prevalence of lymphatic involvement (chylothorax, chylous ascites and/or lymphangioleiomyoma) compared with patients with <800pg/mL (35% vs. 10%, respectively, p=0.02), but with similar prevalence of renal angiomyolipoma. Conclusions: This study reinforced that VEGF-D is a valuable diagnostic biomarker in LAM and is associated with reduced carbon monoxide diffusion capacity and with lymphatic abnormalities. On behalf of the Tuberous Sclerosis, Lymphangioleiomyomatosis and Angiomyolipoma Study Group from The University of Sao Paulo Medical School, Brazil