Circulating midkine in Crohn's disease: clinical implications

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.

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.

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 = 0.49, P < 0.001). Midkine significantly correlated with inflammatory indices: CRP (r = 0.49), erythrocyte sedimentation rate (r = 0.31), leukocytes (r = 0.48), platelets (r = 0.52), albumin (r = -0.49), transferrin (r = -0.47), and IL-6 (r = 0.54); hematological variables: hemoglobin (r = -0.38), hematocrit (r = -0.43), and iron (r = -0.58); angiogenic factors: vascular endothelial growth factor-A (r = 0.42), fibroblast growth factor-2 (r = 0.54), and platelet-derived growth factor-BB (r = 0.57). Midkine elevation corresponded well (r = -0.41) 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%.

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.