Increased serum vascular endothelial growth factor levels in microscopic poly angiitis with pulmonary involvement.
Microscopic polyangiitis (MPA) is a systemic necrotizing vasculitis that affects small vessels, resulting in a wide spectrum of organ involvement including the lungs. However, there are little serological markers that predict its prognosis or severity of pulmonary involvement. Vascular endothelial growth factor (VEGF) is an angiogenic mediator, which has been reported to be elevated in systemic vasculitis. In this study, we measured serum VEGF levels in 22 MPA patients with pulmonary involvement. We also investigated VEGF expression in pulmonary cells using flow cytometry analysis. We found that serum VEGF levels in MPA patients were significantly higher than those in respiratory or urinary tract infection. The serum VEGF levels decreased in parallel with the improvement of MPA symptoms. The serum VEGF levels in MPA patients who died within 5 years were significantly higher than those who survived more than 5 years. The sensitivity of VEGF levels to distinguish MPA patient with poor prognosis from those with good prognosis was 90.9%, and specificity was 81.8% (cutoff value = 802.5 pg/ml). The serum VEGF levels showed significant positive correlation with the composite physiological index, which indicates the severity of pulmonary lesion. In flow cytometry analysis, CD11b positive bronchoalveolar lavage fluid cells expressed VEGF. Immunohistochemically, alveolar macrophages, tissue infiltrating inflammatory cells and alveolar epithelial cells stained positive for VEGF. Measurement of serum VEGF levels in MPA might become one of the markers for prognosis and the severity of pulmonary involvement in MPA. VEGF might contribute to the development of pulmonary lesion of MPA.
Division of Respiratory Medicine, Respiratory and Stress Care Center, Kagoshima University Hospital, Sakuragaoka 8-35-1, Kagoshima 890-8520, Japan.
Jun
J
Iwakawa
Wataru
W
Matsuyama
Shingo
S
Kubota
Hideo
H
Mitsuyama
Takayuki
T
Suetsugu
Masaki
M
Watanabe
Ikkou
I
Higashimoto
Mitsuhiro
M
Osame
Kimiyoshi
K
Arimura
D000368:Aged; D000704:Analysis of Variance; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D049109:Cell Proliferation; D016207:Cytokines / Q000378:metabolism; D004847:Epithelial Cells / Q000473:pathology; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008171:Lung Diseases / Q000150:complications / Q000175:diagnosis* / Q000473:pathology; D008264:Macrophages / Q000473:pathology; D008297:Male; D008833:Microcirculation / Q000502:physiology; D010488:Polyarteritis Nodosa / Q000150:complications / Q000175:diagnosis* / Q000473:pathology; D011379:Prognosis; D011652:Pulmonary Circulation / Q000502:physiology; D012189:Retrospective Studies; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism*
D016207:Cytokines; D042461:Vascular Endothelial Growth Factor A