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Serum proteomic biomarkers diagnostic of knee osteoarthritis.

Publication ,  Conference
Kraus, VB; Reed, A; Soderblom, EJ; Golightly, YM; Nelson, AE; Li, Y-J
Published in: Osteoarthritis Cartilage
March 2024

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 National Institutes of Health (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 (ROC) and precision-recall (PR) curves. RESULTS: RF selected 23 peptides (19 proteins) and body mass index (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% confidence interval [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.

Duke Scholars

Published In

Osteoarthritis Cartilage

DOI

EISSN

1522-9653

Publication Date

March 2024

Volume

32

Issue

3

Start / End Page

329 / 337

Location

England

Related Subject Headings

  • Proteomics
  • Peptides
  • Osteoarthritis, Knee
  • Knee Joint
  • Humans
  • Biomarkers
  • Arthritis & Rheumatology
  • 4207 Sports science and exercise
  • 3202 Clinical sciences
  • 1106 Human Movement and Sports Sciences
 

Citation

APA
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ICMJE
MLA
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Kraus, V. B., Reed, A., Soderblom, E. J., Golightly, Y. M., Nelson, A. E., & Li, Y.-J. (2024). Serum proteomic biomarkers diagnostic of knee osteoarthritis. Osteoarthritis Cartilage, 32(3), 329–337. https://doi.org/10.1016/j.joca.2023.09.007
Kraus, Virginia Byers, Alexander Reed, Erik J. Soderblom, Yvonne M. Golightly, Amanda E. Nelson, and Yi-Ju Li. “Serum proteomic biomarkers diagnostic of knee osteoarthritis.Osteoarthritis Cartilage 32, no. 3 (March 2024): 329–37. https://doi.org/10.1016/j.joca.2023.09.007.
Kraus VB, Reed A, Soderblom EJ, Golightly YM, Nelson AE, Li Y-J. Serum proteomic biomarkers diagnostic of knee osteoarthritis. Osteoarthritis Cartilage. 2024 Mar;32(3):329–37.
Kraus, Virginia Byers, et al. “Serum proteomic biomarkers diagnostic of knee osteoarthritis.Osteoarthritis Cartilage, vol. 32, no. 3, Mar. 2024, pp. 329–37. Pubmed, doi:10.1016/j.joca.2023.09.007.
Kraus VB, Reed A, Soderblom EJ, Golightly YM, Nelson AE, Li Y-J. Serum proteomic biomarkers diagnostic of knee osteoarthritis. Osteoarthritis Cartilage. 2024 Mar;32(3):329–337.
Journal cover image

Published In

Osteoarthritis Cartilage

DOI

EISSN

1522-9653

Publication Date

March 2024

Volume

32

Issue

3

Start / End Page

329 / 337

Location

England

Related Subject Headings

  • Proteomics
  • Peptides
  • Osteoarthritis, Knee
  • Knee Joint
  • Humans
  • Biomarkers
  • Arthritis & Rheumatology
  • 4207 Sports science and exercise
  • 3202 Clinical sciences
  • 1106 Human Movement and Sports Sciences