B Hua1, E H N Olsen2, S Sun3, C N Gudme2, L Wang4, B Vandahl2, K Roepstorff2, M Kjelgaard-Hansen2, B B Sørensen2, Y Zhao1, M A Karsdal3, T Manon-Jensen3. 1. Department of Hematology, Chinese Academy of Medical Sciences (CAMS) & Peking Union Medical College (PUMC), Peking Union Medical College Hospital (PUMCH), Beijing, China. 2. Global Research, Novo Nordisk A/S, Måløv, Denmark. 3. Nordic Bioscience A/S, Herlev, Denmark. 4. Novo Nordisk Research Centre China, Beijing, China.
Abstract
INTRODUCTION: Progressive arthropathy caused by recurrent joint bleeds is a severe complication in haemophilia. AIM: We investigated whether biomarkers of cartilage and bone degradation, and inflammation were altered in haemophilia patients and whether these biomarkers could identify haemophilia patients with arthropathy. METHODS: Serum from 35 haemophilia patients with varying degrees of arthropathy and 43 age- and gender-matched control subjects were analysed. Biomarkers of cartilage degradation (C2M, COMP, CTX-II, ADAMTS5), cartilage formation (PRO-C2), bone formation (PINP), bone resorption (CTX-I) and inflammation (hsCRP, CRPM) were measured by ELISA. Arthropathy was assessed by radiological evaluation (Pettersson score) and physical examination (Gilbert score). RESULTS: In patients with haemophilia, cartilage degradation, measured by C2M, CTX-II and COMP, was increased by 25% (P < 0.05) compared with control subjects. Levels of the cartilage degradation enzyme, ADAMTS5, were 10% lower in haemophilia patients (P < 0.05). Bone formation (PINP) was reduced by 25% (P < 0.05) in haemophilia patients, whereas bone resorption (CTX-I) was increased by 30% (P < 0.001). Acute inflammation (hsCRP) was increased by 50% (P < 0.01), whereas chronic inflammation (CRPM) was decreased by 25% (P < 0.0001). The hsCRP/CRPM ratio was 60% higher (P < 0.001) in haemophilia patients relative to control subjects. A biomarker panel combining C2M, CRPM, and ADAMTS5 could distinguish haemophilia patients from control subjects with 85.3% accuracy (P < 0.0001). We found no strong correlation between biomarkers and radiological and physical examination of the joint. CONCLUSION: Biomarkers detect increased cartilage and bone degradation, and altered inflammatory activity in haemophilia patients with arthropathy. These biomarkers could potentially be used to identify patients with progressing joint disease.
INTRODUCTION: Progressive arthropathy caused by recurrent joint bleeds is a severe complication in haemophilia. AIM: We investigated whether biomarkers of cartilage and bone degradation, and inflammation were altered in haemophiliapatients and whether these biomarkers could identify haemophiliapatients with arthropathy. METHODS: Serum from 35 haemophiliapatients with varying degrees of arthropathy and 43 age- and gender-matched control subjects were analysed. Biomarkers of cartilage degradation (C2M, COMP, CTX-II, ADAMTS5), cartilage formation (PRO-C2), bone formation (PINP), bone resorption (CTX-I) and inflammation (hsCRP, CRPM) were measured by ELISA. Arthropathy was assessed by radiological evaluation (Pettersson score) and physical examination (Gilbert score). RESULTS: In patients with haemophilia, cartilage degradation, measured by C2M, CTX-II and COMP, was increased by 25% (P < 0.05) compared with control subjects. Levels of the cartilage degradation enzyme, ADAMTS5, were 10% lower in haemophiliapatients (P < 0.05). Bone formation (PINP) was reduced by 25% (P < 0.05) in haemophiliapatients, whereas bone resorption (CTX-I) was increased by 30% (P < 0.001). Acute inflammation (hsCRP) was increased by 50% (P < 0.01), whereas chronic inflammation (CRPM) was decreased by 25% (P < 0.0001). The hsCRP/CRPM ratio was 60% higher (P < 0.001) in haemophiliapatients relative to control subjects. A biomarker panel combining C2M, CRPM, and ADAMTS5 could distinguish haemophiliapatients from control subjects with 85.3% accuracy (P < 0.0001). We found no strong correlation between biomarkers and radiological and physical examination of the joint. CONCLUSION: Biomarkers detect increased cartilage and bone degradation, and altered inflammatory activity in haemophiliapatients with arthropathy. These biomarkers could potentially be used to identify patients with progressing joint disease.
Authors: Coline Haxaire; Narine Hakobyan; Tania Pannellini; Camila Carballo; David McIlwain; Tak W Mak; Scott Rodeo; Suchitra Acharya; Daniel Li; Jackie Szymonifka; Xiangqian Song; Sébastien Monette; Alok Srivastava; Jane E Salmon; Carl P Blobel Journal: Blood Date: 2018-05-18 Impact factor: 22.113