Glycoprotein YKL-40: a novel biomarker of chronic graft-vs-host disease activity and severity?

Duraković, Nadira and Krečak, Ivan and Perić, Zinaida and Milošević, Milan and Desnica, Lana and Pulanić, Dražen and Pusic, Iskra and Kušec, Vesna and Vrhovac, Radovan and Pavletic, Steven Z. and Nemet, Damir (2016) Glycoprotein YKL-40: a novel biomarker of chronic graft-vs-host disease activity and severity? Croatian Medical Journal, 57 (3). pp. 239-246. ISSN 0353-9504

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Abstract

AIM: To investigate whether increased YKL-40 levels positively correlate with graft-vs-host disease (cGVHD) activity and severity and if YKL-40 could serve as a disease biomarker. ----- METHODS: This case-control study was conducted at the University Hospital Centre Zagreb from July 2013 to October 2015. 56 patients treated with hematopoietic stem cell transplantation (HSCT) were included: 35 patients with cGVHD and 21 without cGVHD. There was no difference between groups in age, sex, median time from transplant to study enrollment, intensity of conditioning, type of donor, or source of stem cells. Blood samples were collected at study enrollment and YKL-40 levels were measured with ELISA. Disease activity was estimated using Clinician's Impression of Activity and Intensity of Immunosuppression scales and disease severity using Global National Institutes of Health (NIH) score. ----- RESULTS: YKL-40 levels were significantly higher in cGVHD patients than in controls (P=0.003). The difference remained significant when patients with myelofibrosis were excluded from the analysis (P=0.017). YKL-40 level significantly positively correlated with disease severity (P<0.001; correlation coefficient 0.455), and activity estimated using Clinician's Impression of Activity (P=0.016; correlation coefficient 0.412) but not using Intensity of Immunosuppression (P=0.085; correlation coefficient 0.296). ----- CONCLUSION: YKL-40 could be considered a biomarker of cGVHD severity and activity. However, validation in a larger group of patients is warranted, as well as longitudinal testing of YKL-40 levels in patients at risk of developing cGVHD.

Abstract in Croatian

Glikoprotein YKL-40: novi biomarker aktivnosti i težine kronične bolesti presatka protiv domaćina? ----- Cilj: Utvrditi koreliraju li povišene razine YKL-40 pozitivno s aktivnošću i težinom kronične bolesti presatka protiv domaćina (prema engl. chronic graft versus host disease cGVHD) i može li YKL-40 poslužiti kao biomarker za ovu bolest. ----- Postupci: Ova studija parova provedena je u Kliničko-bolničkom centru “Zagreb” u razdoblju od srpnja 2013. do listopada 2015. Uključili smo 56 pacijenata podvrgnutih transplantaciji krvotvornih matičnih stanica (prema engl. hematopoietic stem cell transplantation, HSCT): 35 pacijenata sa cGVHD i 21 bez cGVHD. Među skupinama nije bilo razlika u dobi, spolu, medijanu vremena od transplantacije do uključenja u istraživanje, intenzitetu kondicioniranja, tipu davatelja ili izvoru matičnih stanica. Uzorci krvi prikupljeni su pri uključenju u istraživanje, a razine YKL-40 mjerene su metodom ELISA. Aktivnost bolesti ocijenjena je uz pomoć ljestvica Aktivnost prema dojmu kliničara (prema engl. Clinician’s Impression of Activity) i Intenzitet imunosupresije (prema engl. Intensity of Immunosuppression), a težina bolesti uz pomoć ukupnog izračuna Nacionalnih instituta za zdravlje SAD-a (prema engl. National Institutes of Health, NIH). ----- Rezultati: Razina YKL-40 bila je značajno viša kod pacijenata s cGVHD nego kod kontrolnih ispitanika (P=0,003). Razlika je ostala značajna nakon što su iz analize isključeni pacijenti s mijelofibrozom (P=0,017). Razina YKL-40 značajno je pozitivno korelirala s težinom bolesti (P<0,001; korelacijski koeficijent 0,455), i aktivnošću procijenjenom ljestvicom Aktivnosti prema dojmu kliničara (P=0,016; korelacijski koeficijent 0,412), ali ne i s aktivnošću procijenjenom ljestvicom Intenziteta imunosupresije (P=0.085; korelacijski koeficijent 0,296). ----- Zaključak: Iako je naše istraživanje pokazalo da se YKL-40 može smatrati biomarkerom aktivnosti i težine cGVHD, naše rezultate potrebno je validirati na većoj skupini pacijenata koristeći longitudinalno testiranje YKL-40 razina kod pacijenata kod kojih postoji rizik obolijevanja od cGVHD.

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