engleski

Glycoprotein YKL40 : a Novel Biomarker of Chronic Graft Versus Host Disease Activity?

Introduction: Even though considerable effort has been invested into identifying a reliable biomarker for chronic Graft vs Host Disease (cGVHD), thus far the search has not been successful. Glycoprotein YKL40 has been investigated in various conditions and has been found to be a marker of an ongoing inflammation as well as oncogenic transformation. In a cross-sectional study we investigated the level of YKL-40 in patients suffering from cGVHD in reference to transplanted patients without cGVHD (controls). Material (or patients) and methods: The study was conducted in UHC Zagreb from July 2013 to October 2015. A total of 56 transplanted patients were included, 35 cGVHD patients and 21 controls. Median age was 45 years (range 9- 60) in patient group and 40 years (range 16-59) in control group, there were 18 and 10 females and 17 and 11 males, respectively. Median time from transplant to study enrollment was 463 days (range 61-7853) in patient group, and 428 days (range 190-1770) for controls. Median time from cGVHD diagnosis to enrollment was 154 days (range 1-7125). There were 17 and 8 patients that received myeloablative, 18 and 13 received reduced conditioning in patient and control group, respectively. There was no difference between the source of transplanted cells between groups, 15 and 8 patients that received bone marrow, 20 and 13 received PBSC in patient and control group, respectively. Using global NIH score to estimate disease severity 4 patients were considered to have mild, 15 moderate and 16 severe cGVHD. YKL-40 levels were measured by ELISA and compared between cGVHDpatients and controls. We also tested for correlation in reference to disease severity and activity in cGVHD patients (estimated using Global NIH score, Clinicians impression of activity and Intensity of immunosuppression). Results: YKL- 40 levels were found to be significantly higher in cGVHD patients in reference to controls (median 707 (71-4000) and 314 ng/ml (105-2790) respectively, (P = 0.003). Even if patients with myelofibrosis (condition shown to increase the level of YKL-40) were excluded from analysis (total 6 patients, 3 in cGVHD group and 3 controls), the difference between groups remained statistically significant (P = 0.017). Furthermore, YKL-40 levels were found to correlate significantly with disease severity estimated using global NIH score. YKL-40 levels also positively correlated with Clinician’s impression of activity (P = 0.016) but not with Intensity of immunosuppression (P = 0.085). When tested for correlation with CRP as a measure of active inflammation, no statistically significant correlation was found. Conclusion: Although the number of patients included in this cross-sectional study is limited, our results show that YKL-40 glycoprotein might be a simple and inexpensive biomarker of cGVHD and its activity. However, further investigation is warranted with validation in a larger group of patients, as well as longitudinal testing of YKL-40 glycoprotein levels in patients at risk of developing cGVHD.

chronic graft versus host disease ; biomarker ; glycoprotein YKL40

nije evidentirano