Details:

• Alternative Title:
  Osteoarthritis Cartilage
• Personal Author:
  Kraus, Virginia Byers ; Reed, Alexander ; Soderblom, Erik J ; Golightly, Yvonne M. ; Nelson, Amanda E. ; ... More +

  Kraus, Virginia Byers ; Reed, Alexander ; Soderblom, Erik J ; Golightly, Yvonne M. ; Nelson, Amanda E. ; Li, Yi-Ju Less -
• Description:
  Objective:
  
  To better understand the pathogenesis of knee osteoarthritis (OA) through identification of serum diagnostics.
  
  Design:
  
  We conducted multiple reaction monitoring mass spectrometry analysis of 107 peptides in baseline sera of two cohorts: the Foundation for NIH (n=596 Kellgren-Lawrence (KL) grade 1–3 knee OA participants); and the Johnston County Osteoarthritis Project (n=127 multi-joint controls free of radiographic OA of the hands, hips, knees (bilateral KL=0), and spine). Data were split into (70%) training and (30%) testing sets. Diagnostic peptide and clinical data predictors were selected by random forest (RF); selection was based on association (p<0.05) with OA status in multivariable logistic regression models. Model performance was based on area under the curve (AUC) of receiver operating characteristic and precision-recall (PR) curves.
  
  Results:
  
  RF selected 23 peptides (19 proteins) and BMI as diagnostic of OA. BMI weakly diagnosed OA (ROC-AUC 0.57, PR-AUC 0.812) and only symptomatic OA cases. ACTG was the strongest univariable predictor (ROC-AUC 0.705, PR-AUC 0.897). The final model (8 serum peptides) was highly diagnostic (ROC-AUC 0.833, 95% CI 0.751, 0.905; PR-AUC 0.929, 95% CI 0.876, 0.973) in the testing set and equally diagnostic of non-symptomatic and symptomatic cases (AUCs 0.830–0.835), and not significantly improved with addition of BMI. The STRING database predicted multiple high confidence interactions of the 19 diagnostic OA proteins.
  
  Conclusions:
  
  No more than 8 serum protein biomarkers were required to discriminate knee OA from non-OA. These biomarkers lend strong support to the involvement and cross-talk of complement and coagulation pathways in the development of OA.
  
  
• Subjects:
  [+]

  Biomarkers Humans Knee Joint Osteoarthritis, Knee Peptides Proteomics
• Keywords:
  [+]

  Coagulation Complement Diagnostic Knee Marker Mass Spectrometry Osteoarthritis Proteomics Serum
• Source:
  Osteoarthritis Cartilage. 32(3):329-337
• Pubmed ID:
  37734705
• Pubmed Central ID:
  PMC10925913
• Document Type:
  Journal Article
• Funding:
  P60 AR049465/AR/NIAMS NIH HHSUnited States/ ; P60 AR030701/AR/NIAMS NIH HHSUnited States/ ; R01 AR071450/AR/NIAMS NIH HHSUnited States/ ; P60 AR064166/AR/NIAMS NIH HHSUnited States/ ; U01 DP003206/DP/NCCDPHP CDC HHSUnited States/ ; ... More +

  P60 AR049465/AR/NIAMS NIH HHSUnited States/ ; P60 AR030701/AR/NIAMS NIH HHSUnited States/ ; R01 AR071450/AR/NIAMS NIH HHSUnited States/ ; P60 AR064166/AR/NIAMS NIH HHSUnited States/ ; U01 DP003206/DP/NCCDPHP CDC HHSUnited States/ ; U01DP003206/ACL/ACL HHSUnited States/ ; P30 AG028716/AG/NIA NIH HHSUnited States/ ; P30 AR072580/AR/NIAMS NIH HHSUnited States/ Less -
• Volume:
  32
• Issue:
  3
• Collection(s):
  CDC Public Access
• Main Document Checksum:
  [+]

  urn:sha-512:01f1c0ff847bb6574996197f1a18ef7a13df6add2db415445f3b80c276e9302cad41f1f56580f9d91637bd39d5721820b3e5781a7fbd48069c755c09f571ed7f
• File Type:

• Supporting Files:
  No Additional Files