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

Abstract

Objective We examined gene expression profiles in peripheral blood leukocytes (PBL) of patients with osteoarthritis (OA) in comparison with non-OA controls to evaluate whether gene expression profiles could serve as biomarkers of symptomatic knee OA. We also determined whether candidate genomic biomarkers (PBL expression of inflammatory genes) predict increased risk of disease progression in subjects with symptomatic radiographic knee OA Methods Three independent cohorts of patients with knee OA and non-OA controls were studied: two cohorts (“learning cohort” and “validation cohort”) recruited at New York University Hospital for Joint Diseases (NYUHJD) and one (“validation cohort”) at Duke University Medical Center. PBL gene expression was assessed using Affymetrix microarray and confirmed by QPCR. Radiographic progression at 2 years was assessed in 86 patients Results We identified 173 genes significantly up- or down-regulated (≥1.5-fold change) in OA PBL, at a False Discovery Rate (FDR) of 5%. Cluster analysis revealed two distinct subclasses among these OA patients: those with increased expression (≥2-fold) of IL-1β compared to controls, and those with expression comparable to controls. Overexpression of IL-1β in OA subclasses was validated using QPCR (p<0.0001) in all three cohorts. Patients with the inflammatory “IL-1β signature” had higher pain scores, decreased function and were at higher risk for radiographic progression. Conclusion PBLs from patients with symptomatic knee OA display a characteristic transcriptome profile. Moreover, increased expression of IL-1β identifies a subset of OA patients with increased pain who are at higher risk for radiographic progression.

Influence of IL13 on Periostin Secretion by Synoviocytes in Osteoarthritis

“…OA is the most common form of arthritis and most commonly affects the peripheral joints, particularly the knee. The number of patients with painful knee due to OA continues to increase dramatically with the aging of society: the estimated number of patients exceeds 25 million in the United States (1) and 8 million in Japan (2). The main symptom of OA is pain, which is also the leading factor for patients making lifestyle changes and seeking medical intervention (3).…”

Cross‐Sectional and Longitudinal Associations Between Serum Levels of High‐Sensitivity C‐Reactive Protein, Knee Bone Marrow Lesions, and Knee Pain in Patients With Knee Osteoarthritis

“…Serum levels of interleukin-6 (IL-6), an inflammatory cytokine, predicts radiographic knee OA progression over 5-10 years in women (4) and increased knee cartilage volume loss over 3 years in older adults (5). Similarly, increased serum levels of inflammatory cytokines IL-1b and tumor necrosis factor are associated with increased risk of knee OA progression (6).…”

Effects of Natural Eggshell Membrane (NEM) on Cytokine Production in Cultures of Peripheral Blood Mononuclear Cells: Increased Suppression of Tumor Necrosis Factor-α Levels After In Vitro Digestion

“…through exposure to locally produced mediators of inflammation (i.e., IL-1b, TNF-a, etc.). 16 We were therefore interested in studying cytokine production in peripheral blood mixed cultures including monocytes. This was accomplished through an extended proliferation/cytokine assay, where both digested and undigested NEM preparations with appropriate controls were tested in serial dilutions in the presence and absence of mitogens.…”