Clinical relevance of circulating midkine in ulcerative colitis

Abstract

Background: Non-invasive biochemical markers are needed to support the diagnosis of ulcerative colitis (UC), an incurable disease of unknown pathology. Midkine is an angiogenic cytokine, chemotactic towards neutrophils and macrophages, and a T-regulatory cell suppressor. Methods: Serum midkine was measured immunoenzymatically in 93 UC patients and 108 healthy subjects, and evaluated with respect to disease status, endoscopic, inflammatory and angiogenic activity. The diagnostic value of midkine was compared to Creactive protein (CRP) using receiver operating characteristics (ROC) analysis. Results: Midkine was higher (p-0.0001) in inactive (199 ng/L) and active UC (351 ng/L) compared with controls (93 ng/L), and reflected disease activity (rs0.427, p-0.001). Midkine was correlated with CRP, erythrocyte sedimentation rate (ESR), leukocytes, platelets, interleukin-6, paraoxonase-1, albumin, transferrin, iron, hemoglobin, and hematocrit. Midkine correlated with angiogenic factors: vascular endothelial growth factor-A and platelet-derived growth factor-BB. As a marker of UC, midkine showed a diagnostic accuracy of 85%, sensitivity of 72%, specificity of 82%, whereas CRP showed 83%, 65% and 91%, respectively. As a marker of active UC, midkine showed a diagnostic accuracy of 87%, sensitivity of 84%, specificity of 75%, whereas CRP showed 75%, 63% and 83%, respectively. Combined assessment of midkine and CRP improved sensitivity but substantially decreased specificity. Conclusions: UC is associated with increased circulating midkine, which corresponds with clinical, endoscopic, inflammatory and angiogenic activity, and anemia. Performance of midkine as a marker of UC or active UC was comparable to that of CRP. Clin Chem Lab Med 2009;47:1085-90.

Circulating midkine in malignant and non-malignant colorectal diseases

“…Accordingly, IBD remains one of the key risk factors for CRC [6]. Confirming our previous findings [17,18], we showed midkine to be elevated in IBD patients in the association with the disease exacerbation. Taking into account midkine capability to induce malignant transformation in NIH 3T3 cells [11], it is possible that its recurring elevation in active disease might participate in triggering neoplastic transformation in inflamed colonic mucosa of IBD patients.…”

“…However, available data on circulating midkine in CRC are scanty and limited to small group studies (reviewed in: [16]). Yet, it has been shown to be elevated in IBD, where it correlates with the disease severity [17,18]. This study was designed to compare circulating midkine in patients with malignant and non-malignant conditions of colorectum, assess its association with clinico-pathological features of CRC and compare its potential as disease biomarker with that of CEA as well as to evaluate whether midkine might be an asset for multimarker panels.…”

Elevated plasma midkine and pleiotrophin levels in patients with systemic lupus erythematosus

“…Moreover, midkine may also stimulate inflammatory responses [8], since it has been demonstrated to induce the migration of inflammatory cells [9–11] and suppresses the expansion of regulatory T cell (Treg) by blocking the development of tolerogenic dendritic cells (DCs) [12]. Recently, there is increasing evidence that midkine is implicated in autoimmune and inflammatory diseases, such as rheumatoid arthritis (RA) [13–15], multiple sclerosis (MS) [12, 16–18] and inflammatory bowel disease (IBD) [19, 20]. The serum midkine level could serve as a marker of disease activity in RA and an indicator of a poor prognosis [15].…”

The inflammatory phase of fracture healing is influenced by oestrogen status in mice

“…Mdk was expressed less in sham-operated animals. Because it is known that Mdk expression is associated with IL-6 expression [40] and because IL-6 is a potent inducer for neutrophil recruitment [41], IL-6 expression was evaluated by immunostaining. In sham-mice, IL-6 was expressed in muscle tissue and endosteal cells, but was expressed less in periosteal cells, whereas OVX-mice showed increased expression in periosteal cells adjacent to the fracture gap (Fig.…”

“…Therefore, we suggest that increased IL-6 expression due to the lack of oestrogen might contribute to the increased number of neutrophils in the fracture callus of OVX-mice. In addition, there is some evidence in the literature that Mdk expression may be associated with IL-6 [40, 74]. …”