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A matrix metalloproteinase-generated neoepitope of CRP can identify knee and multi-joint inflammation in osteoarthritis
Arthritis Research & Therapy ( IF 4.9 ) Pub Date : 2021-08-31 , DOI: 10.1186/s13075-021-02610-y
Louie C Alexander 1 , Grant McHorse 1 , Janet L Huebner 1 , Anne-Christine Bay-Jensen 2 , Morten A Karsdal 2 , Virginia B Kraus 1, 3
Affiliation  

To compare C-reactive protein (CRP) and matrix metalloproteinase-generated neoepitope of CRP (CRPM) as biomarkers of inflammation and radiographic severity in patients with knee osteoarthritis. Participants with symptomatic osteoarthritis (n=25) of at least one knee underwent knee radiographic imaging and radionuclide etarfolatide imaging to quantify inflammation of the knees and other appendicular joints. For purposes of statistical analysis, semi-quantitative etarfolatide and radiographic imaging scores were summed across the knees; etarfolatide scores were also summed across all joints to provide a multi-joint synovitis measure. Multiple inflammation and collagen-related biomarkers were measured by ELISA including CRP, CRPM, MMP-generated neoepitopes of type I collagen and type III collagen in serum (n=25), and CD163 in serum (n=25) and synovial fluid (n=18). BMI was associated with CRP (p=0.001), but not CRPM (p=0.753). Adjusting for BMI, CRP was associated with radiographic knee osteophyte score (p=0.002), while CRPM was associated with synovitis of the knee (p=0.017), synovitis of multiple joints (p=0.008), and macrophage marker CD163 in serum (p=0.009) and synovial fluid (p=0.03). CRP correlated with MMP-generated neoepitope of type I collagen in serum (p=0.045), and CRPM correlated with MMP-generated neoepitope of type III collagen in serum (p<0.0001). No biomarkers correlated with age, knee pain, or WOMAC pain. To our knowledge, this is the first time that CRPM has been shown to be associated with knee and multi-joint inflammation based on objective imaging (etarfolatide) and biomarker (CD163) measures. These results demonstrate the capability of biomarker measurements to reflect complex biological processes and for neoepitope markers to more distinctly reflect acute processes than their precursor proteins. CRPM is a promising biomarker of local and systemic inflammation in knee OA that is associated with cartilage degradation and is independent of BMI. CRPM is a potential molecular biomarker alternative to etarfolatide imaging for quantitative assessment of joint inflammation.

中文翻译:

基质金属蛋白酶产生的 CRP 新表位可识别骨关节炎中的膝关节和多关节炎症

比较 C 反应蛋白 (CRP) 和基质金属蛋白酶产生的 CRP 新表位 (CRPM) 作为膝骨关节炎患者炎症和影像学严重程度的生物标志物。至少有一个膝盖有症状性骨关节炎的参与者 (n = 25) 接受了膝关节放射成像和放射性核素依他叶肽成像,以量化膝盖和其他附肢关节的炎症。出于统计分析的目的,半定量 etarfolatide 和放射影像学评分在膝盖上相加;还对所有关节的依他叶肽评分求和,以提供多关节滑膜炎测量。通过ELISA测量多种炎症和胶原相关生物标志物,包括血清中的CRP、CRPM、MMP产生的I型胶原和III型胶原的新表位(n=25),以及血清 (n=25) 和滑液 (n=18) 中的 CD163。BMI 与 CRP(p=0.001)相关,但与 CRPM 无关(p=0.753)。校正 BMI 后,CRP 与影像学膝关节骨赘评分相关(p=0.002),而 CRPM 与膝关节滑膜炎(p=0.017)、多关节滑膜炎(p=0.008)和血清中巨噬细胞标志物 CD163 相关。 p=0.009) 和滑液 (p=0.03)。CRP与血清中MMP产生的I型胶原新表位相关(p=0.045),而CRPM与血清中MMP产生的III型胶原新表位相关(p<0.0001)。没有与年龄、膝关节疼痛或 WOMAC 疼痛相关的生物标志物。据我们所知,这是第一次基于客观成像(etarfolatide)和生物标志物(CD163)测量显示 CRPM 与膝关节和多关节炎症相关。这些结果证明了生物标志物测量反映复杂生物过程的能力,以及新表位标志物比它们的前体蛋白更清楚地反映急性过程的能力。CRPM 是膝关节 OA 局部和全身炎症的一种有前途的生物标志物,与软骨退化有关,并且与 BMI 无关。CRPM 是一种潜在的分子生物标志物,可替代 etarfolatide 成像,用于关节炎症的定量评估。
更新日期:2021-08-31
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