A matrix metalloproteinase-generated neoepitope of CRP can identify knee and multi-joint inflammation in osteoarthritis

Arthritis Research & Therapy

Louie C. Alexander¹  Janet L. Huebner¹  Grant McHorse¹  Virginia B. Kraus²  Anne-Christine Bay-Jensen³  Morten A. Karsdal³ 

[1] Duke Molecular Physiology Institute, Duke University School of Medicine, PO Box 104775, Carmichael Building, 300 N. Duke St, 27701, Durham, NC, USA;Duke Molecular Physiology Institute, Duke University School of Medicine, PO Box 104775, Carmichael Building, 300 N. Duke St, 27701, Durham, NC, USA;Department of Medicine, Duke University School of Medicine, PO Box 104775, Carmichael Building, 300 N. Duke St, 27701, Durham, NC, USA;ImmunoScience, Nordic Bioscience, Herlev, Denmark;

关键词: C-reactive protein (CRP);    Inflammation;    Synovitis;    Osteoarthritis;    Biomarkers;   

DOI  :  10.1186/s13075-021-02610-y

来源: Springer

【 摘 要 】

ObjectiveTo 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.MethodsParticipants 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).ResultsBMI 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.ConclusionsTo 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.

【 授权许可】

CC BY