Kotela Andrzej, Wojdasiewicz Piotr, Łęgosz Paweł, Sarzyńska Sylwia, Drela Katarzyna, Pulik Łukasz, Kaleta Beata, Kniotek Monika, Borysowski Jan, Poniatowski Łukasz A, Kotela Ireneusz
Department of Orthopaedics and Traumatology, 1st Faculty of Medicine, Medical University of Warsaw, Warsaw, Poland.
Department of Orthopaedics and Traumatology, Central Clinical Hospital of the Ministry of the Interior and Administration, Warsaw, Poland.
Clin Exp Pharmacol Physiol. 2019 Apr;46(4):373-379. doi: 10.1111/1440-1681.13054. Epub 2018 Dec 21.
Haemophilia A and B are rarely occurring X chromosome-linked congenital coagulation disorders dominated by spontaneous joint bleedings and chronic synovitis, leading to development of haemophilic arthropathy (HA). Progranulin (PGRN) is a growth factor with anti-inflammatory and immunomodulatory properties. PGRN is an important molecule in the pathogenesis of osteoarthritis (OA) and rheumatological disorders. This study was aimed at investigating the potential role of PGRN in the mechanisms underlying the pathogenesis of HA. The serum levels of PGRN were measured by enzyme-linked immunosorbent assay (ELISA) in patients with end-stage knee joint HA (n = 20) and end-stage primary knee joint OA (n = 20) who met the inclusion and exclusion criteria. The clinical and radiological assessment of disease severity was evaluated by the Knee Society Score (KSS) and Kellgren-Lawrence scale. Median PGRN levels in HA patients was 349.1 ng/mL (232.8-415.6 ng/mL) and in OA patients 148.3 ng/mL (112.1-275.3 ng/mL) with statistically significant differences between both groups (P < 0.015). Further analysis revealed no correlation between PGRN levels and any of the patient demographics and clinical parameters. This study demonstrates increased PGRN serum levels in patients with HA and provides new insights into the mechanisms underlying the pathogenesis of HA indicating a new potential target for therapeutic intervention.
甲型和乙型血友病是罕见的X染色体连锁先天性凝血障碍,以自发性关节出血和慢性滑膜炎为主,可导致血友病性关节病(HA)的发展。颗粒蛋白前体(PGRN)是一种具有抗炎和免疫调节特性的生长因子。PGRN是骨关节炎(OA)和风湿性疾病发病机制中的重要分子。本研究旨在探讨PGRN在HA发病机制中的潜在作用。采用酶联免疫吸附测定(ELISA)法测定符合纳入和排除标准的终末期膝关节HA患者(n = 20)和终末期原发性膝关节OA患者(n = 20)的血清PGRN水平。采用膝关节协会评分(KSS)和凯尔格伦-劳伦斯量表对疾病严重程度进行临床和影像学评估。HA患者的PGRN水平中位数为349.1 ng/mL(232.8 - 415.6 ng/mL),OA患者为148.3 ng/mL(112.1 - 275.3 ng/mL),两组间差异有统计学意义(P < 0.015)。进一步分析显示,PGRN水平与患者的任何人口统计学和临床参数均无相关性。本研究表明HA患者血清PGRN水平升高,并为HA发病机制提供了新的见解,提示了一个新的潜在治疗干预靶点。