title: CCL3 serves as a potential plasma biomarker in knee degeneration (osteoarthritis).
abstract: OBJECTIVE
  To explore the ability of chemokines in plasma to detect the presence of pre-X-rays defined knee degeneration and the extent (burden).
  
  
  METHODS
  A total of 181 subjects (75 control subjects, 47 pre-X-KD patients and 50 X-KOA patients) were included and subdivided into three subgroups. Articular cartilage loss in pre-X-KD patients were scored on the basis of the ICRS classification during the arthroscopy or documented on MRI with chondral WORMS. The severity of X-KOA was graded using the Kellgren-Lawrence classification through the posterior-anterior knee X-rays. The concentrations of the inflammatory cytokines and chemokines in plasma were quantified using Luminex microbead-based suspension array (SA) and were cross-validated by enzyme-linked immunosorbent assay (ELISA).
  
  
  RESULTS
  CCL3 in plasma showed the highest ability to discriminate pre-X-KD patients from the controls with an AUC of 0.799. At a cutoff value of 0.168 pg/ml, the sensitivity was 70.21%, the specificity was 96.00%, the positive predictive value was 91.67% and the negative predictive value was 83.72%. As to define disease burden, the plasma levels of resistin, IL6, IL8, CCL3 and CCL4 showed significant association with the severity of X-rays defined knee OA, with regard to the KL classification. Moreover, significant elevation of IL6, IL8, CCL3 and CCL4 levels in plasma were observed in severe knee OA patients (KL grade IV) compared with those with pre-X-KD (KL grade 0-I).
  
  
  CONCLUSIONS
  We firstly showed that the plasma CCL3 could be potential serum biomarker for knee OA with the capacity to detect pre-X-rays defined changes and stage the severity of damage in knee.
authors.affiliation: Department of Orthopaedic Surgery, First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong 510080, PR China.
authors.forename: X Y
authors.initials: XY
authors.lastname: Zhao
authors.affiliation: Department of Orthopaedic Surgery, First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong 510080, PR China.
authors.forename: Z B
authors.initials: ZB
authors.lastname: Yang
authors.affiliation: Department of Orthopaedic Surgery, First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong 510080, PR China.
authors.forename: Z J
authors.initials: ZJ
authors.lastname: Zhang
authors.affiliation: Department of Orthopaedic Surgery, First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong 510080, PR China. Electronic address: Zhiqi_zh@163.com.
authors.forename: Z Q
authors.initials: ZQ
authors.lastname: Zhang
authors.affiliation: Department of Orthopaedic Surgery, First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong 510080, PR China.
authors.forename: Y
authors.initials: Y
authors.lastname: Kang
authors.affiliation: Department of Orthopaedic Surgery, First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong 510080, PR China.
authors.forename: G X
authors.initials: GX
authors.lastname: Huang
authors.affiliation: Department of Thyroid and Breast Surgery, First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong 510080, PR China.
authors.forename: S W
authors.initials: SW
authors.lastname: Wang
authors.affiliation: Department of Laboratory Medicine, First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong 510080, PR China.
authors.forename: H
authors.initials: H
authors.lastname: Huang
authors.affiliation: Department of Orthopaedic Surgery, First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong 510080, PR China. Electronic address: liaoweiming29@163.com.
authors.forename: W M
authors.initials: WM
authors.lastname: Liao
mesh_terms: D000328:Adult; D015415:Biomarkers / Q000097:blood; D016022:Case-Control Studies; D054405:Chemokine CCL3 / Q000097:blood*; D054407:Chemokine CCL4 / Q000097:blood; D005260:Female; D006801:Humans; D015850:Interleukin-6 / Q000097:blood; D016209:Interleukin-8 / Q000097:blood; D008297:Male; D008875:Middle Aged; D020370:Osteoarthritis, Knee / Q000097:blood* / Q000000981:diagnostic imaging*; D011237:Predictive Value of Tests; D011859:Radiography; D052243:Resistin / Q000097:blood; D012680:Sensitivity and Specificity; D012720:Severity of Illness Index
chemical_list: D015415:Biomarkers; C515429:CCL3 protein, human; C066507:CCL4 protein, human; D054405:Chemokine CCL3; D054407:Chemokine CCL4; D015850:Interleukin-6; D016209:Interleukin-8; D052243:Resistin
keywords: Biomarker; Chemokines; Knee degeneration (osteoarthritis); Plasma