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Increased interleukin-1β gene expression in peripheral blood leukocytes is associated with increased pain and predicts risk for progression of symptomatic knee osteoarthritis.

Publication ,  Journal Article
Attur, M; Belitskaya-Lévy, I; Oh, C; Krasnokutsky, S; Greenberg, J; Samuels, J; Smiles, S; Lee, S; Patel, J; Al-Mussawir, H; McDaniel, G ...
Published in: Arthritis Rheum
July 2011

OBJECTIVE: To evaluate whether gene expression profiles could serve as biomarkers of symptomatic knee osteoarthritis (OA) by examining gene expression profiles in peripheral blood leukocytes (PBLs) from patients with OA compared with those from non-OA controls, and to determine whether candidate genomic biomarkers (PBL expression of inflammatory genes) predict an increased risk of disease progression in patients with symptomatic radiographic knee OA. METHODS: Three independent cohorts of patients with knee OA and non-OA control subjects were studied. Two cohorts (a learning cohort and a validation cohort) were recruited at New York University Hospital for Joint Diseases (NYUHJD), and 1 cohort (a validation cohort) was recruited at Duke University Medical Center. PBL gene expression was assessed using Affymetrix microarray and was confirmed by quantitative polymerase chain reaction (qPCR). Radiographic progression at 2 years was assessed in 86 patients. RESULTS: We identified 173 genes that were significantly up-regulated or down-regulated (≥1.5-fold change) in OA PBLs, at a false discovery rate of 5%. Cluster analysis revealed 2 distinct subgroups among the patients with OA: those in whom the expression of interleukin-1β (IL-1β) was increased ≥2-fold compared with controls, and those in whom the expression of IL-1β was comparable with that in controls. Overexpression of IL-1β in these OA subclasses was validated using qPCR in all 3 cohorts. Patients with the inflammatory "IL-1β signature" had higher pain scores and decreased function and were at higher risk of radiographic progression of OA. CONCLUSION: PBLs from patients with symptomatic knee OA display a characteristic transcriptome profile. Moreover, increased expression of IL-1β identifies a subset of patients with OA who have increased pain and are at higher risk of radiographic progression of OA.

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Published In

Arthritis Rheum

DOI

EISSN

1529-0131

Publication Date

July 2011

Volume

63

Issue

7

Start / End Page

1908 / 1917

Location

United States

Related Subject Headings

  • Reverse Transcriptase Polymerase Chain Reaction
  • Radiography
  • Pain Measurement
  • Pain
  • Osteoarthritis, Knee
  • Oligonucleotide Array Sequence Analysis
  • Middle Aged
  • Male
  • Leukocytes
  • Knee Joint
 

Citation

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Attur, M., Belitskaya-Lévy, I., Oh, C., Krasnokutsky, S., Greenberg, J., Samuels, J., … Abramson, S. B. (2011). Increased interleukin-1β gene expression in peripheral blood leukocytes is associated with increased pain and predicts risk for progression of symptomatic knee osteoarthritis. Arthritis Rheum, 63(7), 1908–1917. https://doi.org/10.1002/art.30360
Attur, Mukundan, Ilana Belitskaya-Lévy, Cheongeun Oh, Svetlana Krasnokutsky, Jeffrey Greenberg, Jonathan Samuels, Stephen Smiles, et al. “Increased interleukin-1β gene expression in peripheral blood leukocytes is associated with increased pain and predicts risk for progression of symptomatic knee osteoarthritis.Arthritis Rheum 63, no. 7 (July 2011): 1908–17. https://doi.org/10.1002/art.30360.
Attur M, Belitskaya-Lévy I, Oh C, Krasnokutsky S, Greenberg J, Samuels J, et al. Increased interleukin-1β gene expression in peripheral blood leukocytes is associated with increased pain and predicts risk for progression of symptomatic knee osteoarthritis. Arthritis Rheum. 2011 Jul;63(7):1908–17.
Attur, Mukundan, et al. “Increased interleukin-1β gene expression in peripheral blood leukocytes is associated with increased pain and predicts risk for progression of symptomatic knee osteoarthritis.Arthritis Rheum, vol. 63, no. 7, July 2011, pp. 1908–17. Pubmed, doi:10.1002/art.30360.
Attur M, Belitskaya-Lévy I, Oh C, Krasnokutsky S, Greenberg J, Samuels J, Smiles S, Lee S, Patel J, Al-Mussawir H, McDaniel G, Kraus VB, Abramson SB. Increased interleukin-1β gene expression in peripheral blood leukocytes is associated with increased pain and predicts risk for progression of symptomatic knee osteoarthritis. Arthritis Rheum. 2011 Jul;63(7):1908–1917.
Journal cover image

Published In

Arthritis Rheum

DOI

EISSN

1529-0131

Publication Date

July 2011

Volume

63

Issue

7

Start / End Page

1908 / 1917

Location

United States

Related Subject Headings

  • Reverse Transcriptase Polymerase Chain Reaction
  • Radiography
  • Pain Measurement
  • Pain
  • Osteoarthritis, Knee
  • Oligonucleotide Array Sequence Analysis
  • Middle Aged
  • Male
  • Leukocytes
  • Knee Joint