van Vulpen L F D, van Meegeren M E R, Roosendaal G, Jansen N W D, van Laar J M, Schutgens R E G, Mastbergen S C, Lafeber F P J G
Van Creveldkliniek, University Medical Center (UMC) Utrecht, Utrecht, The Netherlands; Department of Rheumatology & Clinical Immunology, University Medical Center (UMC) Utrecht, Utrecht, The Netherlands.
Van Creveldkliniek, University Medical Center (UMC) Utrecht, Utrecht, The Netherlands.
Osteoarthritis Cartilage. 2015 Jan;23(1):63-9. doi: 10.1016/j.joca.2014.09.008. Epub 2014 Sep 16.
Evaluation whether biomarkers of joint damage are sensitive to change shortly after a joint bleed in hemophilia patients and in a canine model of blood-induced joint damage.
Blood and urine samples were collected from 10 hemophilia patients after they reported a joint bleed: within 2 days, after 3-5 days, and 12-14 days. Additionally, 90 days after the bleed a blood and urine sample was taken and considered to represent baseline condition. Commercial serum and urine biomarker assays were performed: urinary C-terminal telopeptide of type II collagen (uCTX-II), serum cartilage oligomeric matrix protein (sCOMP), serum cartilage cleavage product C1,2C, and serum chondroitin sulfate 846 (sCS846). The same panel of biomarkers was explored in dogs (n = 7) after induction of a first joint bleed by intra-articular blood injections. Biosamples were collected at baseline, day 2, 1 and 2 weeks later.
In hemophilia patients, levels of uCTX-II and sCS846 increased 5 days after joint bleeding when compared with baseline (+52%; P = 0.021 and +14%; P = 0.011, respectively). In dogs, uCTX-II increased statistically significant from day 2 to day 7 (from 75% to 155% of baseline; P = 0.018), and sCOMP from baseline to day 2 (+46%; P = 0.028).
This study demonstrates that biochemical markers of joint tissue damage increase shortly after a single joint bleed, both in humans with established hemophilic arthropathy (HA) and in an animal model of joint damage upon a first joint bleed. Biomarkers might be useful in monitoring the impact of a joint bleed and in evaluation of treatment of such bleeds.
评估关节损伤生物标志物在血友病患者关节出血后不久以及在血液诱导性关节损伤犬模型中对变化的敏感性。
在10名血友病患者报告关节出血后采集血液和尿液样本：在2天内、3 - 5天后以及12 - 14天后。此外，出血90天后采集血液和尿液样本并视为代表基线情况。进行了商业血清和尿液生物标志物检测：尿II型胶原C端肽（uCTX-II）、血清软骨寡聚基质蛋白（sCOMP）、血清软骨裂解产物C1,2C以及血清硫酸软骨素846（sCS846）。通过关节内注射血液诱导首次关节出血后，在犬（n = 7）中探究了同一组生物标志物。在基线、第2天、1周和2周后采集生物样本。
在血友病患者中，与基线相比，关节出血5天后uCTX-II和sCS846水平升高（分别为+52%；P = 0.021和+14%；P = 0.011）。在犬中，uCTX-II从第2天到第7天有统计学显著升高（从基线的75%升至155%；P = 0.018），sCOMP从基线到第2天升高（+46%；P = 0.028）。
本研究表明，在患有已确诊血友病性关节病（HA）的人类以及首次关节出血后的关节损伤动物模型中，单次关节出血后不久关节组织损伤的生化标志物都会升高。生物标志物可能有助于监测关节出血的影响以及评估此类出血的治疗效果。
