Background/Purpose: Midkine (MK) is a heparin-binding growth factor, promotes growth, survival, and migration of various cells. Recently several reports show that MK may also play an important role in chronic inflammatory disorders including, kidney diseases, hypoxia-induced angiogenesis and rheumatoid arthritis. To evaluate the role of MK in vasculitis syndrome, we measured the serum level of MK in patients with vasculitis and detected the expression of MK in vasculitis tissues.Methods: Thirty-two patients with active vasculitis syndrome (17 microscopic polyangiitis; MPA, 3 granulomatosis with polyangiits; GPA, 3 eosinophilic granulomatosis with polyangitis; EGPA, 4 giant cell arteritis; GCA, 3 Takayasu arteritis; TA and 2 polyarteritis nodosa; PAN) before treatment, and 10 healthy subjects as control were included in this study. Serum level of MK was measured by enzyme-linked immunosorbent assay (ELISA). Expression of MK was detected by immunohistchemical methods in several biopsy tissues of patients with vasculitis syndrome.Results: Serum levels of MK in patients with vasculitis syndrome were significantly higher than that of healthy control (Vasculitis syndrome, 2014 (mean)±1839 (S.D.) pg/ml; Control 284 ± 57 pg/ml, (P <0.01). Mean age of vasculitis patients was 65.6±17.4, and disease duration was 2.2±1.6 months. Mean disease activity of these patients expressed by vsculitis activity score (BVAS) was 16.5±9.1 and mean vasculitis damage index (VDI) of these patients was 1.8±1.3. Both of BVAS and VDI of patients with vasculitis syndrome were not correlated with serum MK levels. Serum levels of MK in these patients with were; MPA :3615±4080,GPA: 960±23, EGPA: 989±698, GCA:1080±997,TA:495±272, and PAN:507±102pg/ml. Levels of serum MK in patients with poor prognosis were significantly higher than that of patients with good prognosis (dead: 4608.0±4406.1pg/ml, survival: 1891.9±2933.4pg/ml, Mann-Whitney U test p<0.05). Optimal cut off value of serum MK as indicator of prognosis was 1797 pg/ml in patients with vasculitis syndrome using receiver operating characteristic curve analysis (high MK group n=22, low MK group n=10). Life table analysis of these patients by Kaplan-Meier method revealed that survival rate of high MK group was significantly shorter than that of low MK group (log-rank test P <0.05). All dead patients were complicated with pulmonary involvements. MK was detected in renal tubular epithelial cells, mesangial cells, but not in inflammatory cells and vascular cells in renal tissues of vasculitis patients. MK also highly expressed in dermal epithelial cells of vasculitis skin biopsy specimens.Conclusion: It is suggested that MK might play an important role in pathogenesis of vasculitis syndrome. Since increased serum MK level was associated with poor prognosis, it might also be a novel prognostic factor of vasculitis syndrome.
Disclosure:
Y. Kusunoki,
None;
Y. Okano,
None;
N. Kusunoki,
None;
N. Fujio,
None;
M. Kawazoe,
None;
E. Shindo,
None;
K. Shikano,
None;
M. Kaburaki,
None;
S. Muraoka,
None;
K. Kitahara,
None;
K. Kaneko,
None;
N. Tanaka,
None;
T. Yamamoto,
None;
K. Takagi,
None;
T. Hasunuma,
None;
H. Endo,
None;
S. Kawai,
None.
« Back to 2013 ACR/ARHP Annual Meeting
ACR Meeting Abstracts - https://acrabstracts.org/abstract/midkine-is-a-novel-prognostic-factor-in-patients-with-vasculitis-syndrome/