Background: A noninvasive marker facilitating differential diagnosis in Crohn's disease (CD) is sought after. Midkine is a heparin-binding growth factor of angiogenic and chemotactic properties, positively evaluated as a tumor marker, and a possible association with CD has not yet been investigated.
Methods:
Circulating midkine was measured in 91 CD patients and 108 controls and related to disease clinical and biochemical activity, inflammation severity, and angiogenesis. Midkine diagnostic value in comparison with C-reactive protein (CRP) was evaluated by receiver operating characteristic (ROC) analysis.
Results: Circulating midkine was elevated both in quiescent and active disease compared to controls (147, 506, and 93 pg/mL, respectively), and corresponded well with disease activity (r ΒΌ 0.49, P < 0.001). Midkine significantly correlated with inflammatory indices: CRP (r ΒΌ 0.49), erythrocyte sedimentation rate (r ΒΌ 0.31), leukocytes (r ΒΌ 0.48), platelets (r ΒΌ 0.52), albumin (r ΒΌ Γ0.49), transferrin (r ΒΌ Γ0.47), and IL-6 (r ΒΌ 0.54); hematological variables: hemoglobin (r ΒΌ Γ0.38), hematocrit (r ΒΌ Γ0.43), and iron (r ΒΌ Γ0.58); angiogenic factors: vascular endothelial growth factor-A (r ΒΌ 0.42), fibroblast growth factor-2 (r ΒΌ 0.54), and platelet-derived growth factor-BB (r ΒΌ 0.57). Midkine elevation corresponded well (r ΒΌ Γ0.41) with the drop in paraoxonase-1 activity-a quorum-quenching factor. Midkine as a marker of active CD had sensitivity and specificity of 86% and 97%, respectively, whereas CRP was 83% and 92%.
Conclusions: CD is associated with an elevation of midkine, which corresponds well with disease activity and reflects the severity of inflammatory response and exacerbation of pathological angiogenesis. Midkine performance as a disease marker was slightly better than that of CRP. Its high specificity and likelihood ratios for positive test results might recommend midkine as a possible ''ruling in'' marker in CD.