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Low‐Grade Inflammation in Symptomatic Knee Osteoarthritis: Prognostic Value of Inflammatory Plasma Lipids and Peripheral Blood Leukocyte Biomarkers
Author(s) -
Attur Mukundan,
Krasnokutsky Svetlana,
Statnikov Alexander,
Samuels Jonathan,
Li Zhiguo,
Friese Olga,
Hellio Le GraverandGastineau MariePierre,
Rybak Leon,
Kraus Virginia B.,
Jordan Joanne M.,
Aliferis Constantin F.,
Abramson Steven B.
Publication year - 2015
Publication title -
arthritis and rheumatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.106
H-Index - 314
eISSN - 2326-5205
pISSN - 2326-5191
DOI - 10.1002/art.39279
Subject(s) - medicine , osteoarthritis , inflammation , gastroenterology , pathogenesis , confidence interval , area under the curve , prospective cohort study , pathology , alternative medicine
Objective Inflammatory mediators, such as prostaglandin E 2 (PGE 2 ) and interleukin‐1β (IL‐1β), are produced by osteoarthritic (OA) joint tissue, where they may contribute to disease pathogenesis. We undertook the present study to examine whether inflammation, evidenced in plasma and peripheral blood leukocytes (PBLs), reflects the presence, progression, or specific symptoms of symptomatic knee OA. Methods Patients with symptomatic knee OA were enrolled in a 24‐month prospective study of radiographic progression. Standardized knee radiographs were obtained at baseline and 24 months. At baseline, levels of the plasma lipids PGE 2 and 15‐hydroxyeicosatetraenoic acid (15‐HETE) were measured, and transcriptome analysis of PBLs was performed by microarray and quantitative polymerase chain reaction. Results Baseline PGE 2 synthase (PGES) levels determined by PBL microarray gene expression and plasma PGE 2 levels distinguished patients with symptomatic knee OA from non‐OA controls (area under the receiver operating characteristic curve [AUC] 0.87 and 0.89, respectively, P < 0.0001). Baseline plasma 15‐HETE levels were significantly elevated in patients with symptomatic knee OA versus non‐OA controls ( P < 0.0195). In the 146 patients who completed the 24‐month study, elevated baseline expression of IL‐1β, tumor necrosis factor α, and cyclooxygenase 2 (COX‐2) messenger RNA in PBLs predicted higher risk of radiographic progression as evidenced by joint space narrowing (JSN). In a multivariate model, AUC point estimates of models containing COX‐2 in combination with demographic traits overlapped the confidence interval of the base model in 2 of the 3 JSN outcome measures (JSN >0.0 mm, JSN >0.2 mm, and JSN >0.5 mm; AUC 0.62–0.67). Conclusion The inflammatory plasma lipid biomarkers PGE 2 and 15‐HETE identify patients with symptomatic knee OA, and the PBL inflammatory transcriptome identifies a subset of patients with symptomatic knee OA who are at increased risk of radiographic progression. These findings may reflect low‐grade inflammation in OA and may be useful as diagnostic and prognostic biomarkers in clinical development of disease‐modifying OA drugs.