Plasma levels of interleukin-1 receptor antagonist (IL1Ra) predict radiographic progression of symptomatic knee osteoarthritis

Abstract

Objective Pro- and anti-inflammatory mediators, such as IL-1β and IL1Ra, are produced by joint tissues in osteoarthritis (OA), where they may contribute to pathogenesis. We examined whether inflammatory events occurring within joints are reflected in plasma of patients with symptomatic knee osteoarthritis (SKOA). Design 111 SKOA subjects with medial disease completed a 24-month prospective study of clinical and radiographic progression, with clinical assessment and specimen collection at 6-month intervals. The plasma biochemical marker IL1Ra was assessed at baseline and 18 months; other plasma biochemical markers were assessed only at 18 months, including IL-1β, TNFα, VEGF, IL-6, IL-6Rα, IL-17A, IL-17A/F, IL-17F, CRP, sTNF-RII, and MMP-2. Results In cross-sectional studies, WOMAC (total, pain, function) and plasma IL1Ra were modestly associated with radiographic severity after adjustment for age, gender and BMI. In addition, elevation of plasma IL1Ra predicted joint space narrowing (JSN) at 24 months. BMI did associate with progression in some but not all analyses. Causal graph analysis indicated a positive association of IL1Ra with JSN; an interaction between IL1Ra and BMI suggested either that BMI influences IL1Ra or that a hidden confounder influences both BMI and IL1Ra. Other protein biomarkers examined in this study did not associate with radiographic progression or severity. Conclusions Plasma levels of IL1Ra were modestly associated with the severity and progression of symptomatic knee osteoarthritis in a causal fashion, independent of other risk factors. The findings may be useful in the search for prognostic biomarkers and development of disease-modifying OA drugs.

Review of Prospects of Biological Fluid Biomarkers in Osteoarthritis

“…Moreover, soluble TNF receptors (TNF-Rs) in serum from older obese patients with knee OA show a positive correlation with pain, joint stiffness and radiographic severity [79]. For IL-1, it has been demonstrated that the level of a natural antagonist of interleukin-1 (IL-1Ra) in plasma is associated with the severity and progression of symptomatic knee OA as evaluated by JSN, suggesting IL-1Ra as a predictive marker for radiographic OA progression [77]. …”

Association of periodontitis with radiographic knee osteoarthritis

“…Another study reported that serum IL‐6 and TNF‐α levels were associated with radiographic knee OA and cartilage loss of the knee joints . Additionally, plasma interleukin‐1 receptor antagonist (IL‐1Ra) levels can predict joint space narrowing in knee OA . Baseline and increasing levels of IL‐6 and TNF‐α in synovial fluid were also related to the progression of radiographic knee OA .…”

Osteoarthritis Year in Review 2016: biomarkers (biochemical markers)

“…In a 24 month prospective cohort of symptomatic knee OA patients, the authors confirmed that elevated baseline levels of IL-1b, TNF-a and COX-2 peripheral blood transcripts predicted a higher risk of JSW narrowing 57 . In another study that analyzed samples from the same 24-month prospective cohort of symptomatic knee OA patients, the authors found that plasma levels of interleukin-1 receptor antagonist (IL-1Ra) were positively associated with the severity and progression of knee OA 59 .…”