Identification and characterisation of osteoarthritis patients with inflammation derived tissue turnover

Abstract

Objectives: Osteoarthritis (OA) is a degenerative disease with a subset of patients experiencing joint inflammation, but C-reactive protein (CRP) has shown limited use in OA as a diagnostic marker. The aim was to identify subpopulations of patients with high or low levels of acute (high sensitive CRP (hsCRP)) and/or matrix metalloproteinase (MMP) derived inflammation (CRPM) and investigate the subpopulations' association with biomarkers of collagen degradation and Kellgren-Lawrence (KL) score.

Methods: hsCRP, CRPM and MMP-degraded type I, II and III collagen (type I collagen degraded by MMP (C1M), type II collagen degraded by MMP (C2M) and type III collagen degraded by MMP (C3M)) were quantified by enzyme linked immunosorbent assays (ELISA) in serum of 342 patients with symptomatic knee OA of which 60 underwent total knee replacement (TKR). KL was obtained. Patients were divided into quartiles by hsCRP and CRPM levels, where Q1 and Q4 were low or high in both. The biomarker levels of healthy adults provided in the ELISA kits were used as reference level.

Results: hsCRP was elevated in TKR (5.9(3.6-8.2 95% confidence interval (CI)) μg/mL) compared to reference level (3 μg/mL), while CRPM was highly elevated with OA independent of KL (10-14 ng/mL) compared to reference level (5 ng/mL). Q4 had higher KL than Q1 (P < 0.001), Q2 (P = 0.017) and Q3 (P < 0.001). C1M, C2M and C3M were lowest in Q1. C1M was elevated in Q3 compared to Q2 (P < 0.001), whereas C3M was lower (P = 0.019).

Conclusion: A bigger proportion of patients were elevated in CRPM compared to hsCRP, indicating MMP-derived inflammation as a component of OA. Moreover, the levels of MMP-degraded collagens differed between the subgroups segregated by inflammation, indicating distinctively different subpopulation selected by inflammation.

Keywords: Biochemical markers of inflammation and collagen turnover; Inflammation; Matrix metalloproteinases; Osteoarthritis; Selection of the right patients for the right treatment.