Although osteoarthritis (OA) was formerly considered a non-inflammatory joint disease, it’s now well-appreciated that inflammatory mediators, such as PGE2 and IL-1β, are produced by osteoarthritic joint tissues and have been implicated in its pathogenesis. These researchers examined whether inflammation, as reflected by the gene expression profile of peripheral blood leukocytes (PBLs), was indicative of OA progression or symptoms in patients with 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. Biomarkers assessed at baseline included plasma lipids PGE2 and 15-HETE, and transcriptome analysis of peripheral blood leukocytes by microarray and qPCR.
Results: Baseline PGE synthase expression by peripheral blood leukocytes, as assessed by microarray gene profiling, and plasma PGE2 distinguished symptomatic knee OA patients from non-OA controls (AUCs 0.87 and 0.89 respectively, p<0.0001). Baseline plasma 15-HETE was significantly elevated in symptomatic knee OA compared with non-OA controls (p<0.019). In the 146 patients who completed the 24-month study, elevated baseline expression of IL-1β, TNFα and COX-2 mRNA in peripheral blood leukocytes predicted higher risk for radiographic progression by joint space narrowing. In a multivariate model, AUC point estimates of models containing COX-2 in combination with demographic traits overlap the confidence interval of the base model in two out of the three JSN outcome measures (JSN >0.0mm, >0.2mm and >0.5mm, AUC=0.62–0.67).
Conclusion: Increased plasma levels of the inflammatory biomarkers PGE2 and 15-HETE, as well as peripheral blood leukocyte transcriptome analyses, hold promise as early diagnostic and prognostic tests for OA. Further, inflammatory biomarkers can be used to identify subgroups among subjects with clinical knee OA in whom the disease progresses at different rates. Inflammatory biomarkers may be useful in the future to stratify patients and develop personalized care for OA.
Excerpted and adapted from:
Attur M, Krasnokutsky S, Statnikov A, et al. Low-grade inflammation in symptomatic knee osteoarthritis: Prognostic value of inflammatory plasma lipids and peripheral blood leukocyte biomarkers. Arthritis Rheumatol. 2015 Nov;67(11):2905–2915.