Identification and characterisation of osteoarthritis patients with inflammation derived tissue turnover.
OBJECTIVE
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).


CONCLUSIONS
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.
Rheumatology, Biomarkers and Research, Nordic Bioscience, Herlev, Denmark. Electronic address: aso@nordicbioscience.com.
A S
AS
Siebuhr
Center for Sensory-Motor Interaction (SMI), Department of Health Science and Technology, Faculty of Medicine, Aalborg University, Denmark; Aalborg University Hospital, Department of Orthopaedic Surgery, Aalborg, Denmark.
K K
KK
Petersen
Center for Sensory-Motor Interaction (SMI), Department of Health Science and Technology, Faculty of Medicine, Aalborg University, Denmark.
L
L
Arendt-Nielsen
Center for Sensory-Motor Interaction (SMI), Department of Health Science and Technology, Faculty of Medicine, Aalborg University, Denmark.
L L
LL
Egsgaard
Center for Clinical and Basic Research and C4Pain, Aalborg, Denmark.
T
T
Eskehave
Rheumatology, Biomarkers and Research, Nordic Bioscience, Herlev, Denmark; Center for Clinical and Basic Research and C4Pain, Aalborg, Denmark.
C
C
Christiansen
Aalborg University Hospital, Department of Orthopaedic Surgery, Aalborg, Denmark.
O
O
Simonsen
Center for Clinical and Basic Research and C4Pain, Aalborg, Denmark.
H C
HC
Hoeck
Rheumatology, Biomarkers and Research, Nordic Bioscience, Herlev, Denmark.
M A
MA
Karsdal
Rheumatology, Biomarkers and Research, Nordic Bioscience, Herlev, Denmark.
A C
AC
Bay-Jensen
D000368:Aged; D019645:Arthroplasty, Replacement, Knee; D015415:Biomarkers / Q000097:blood; D024042:Collagen Type I / Q000097:blood; D024043:Collagen Type II / Q000097:blood; D024061:Collagen Type III / Q000097:blood; D003430:Cross-Sectional Studies; D005260:Female; D006801:Humans; D008297:Male; D020782:Matrix Metalloproteinases / Q000097:blood; D008875:Middle Aged; D020370:Osteoarthritis, Knee / Q000097:blood / Q000150:complications* / Q000175:diagnosis / Q000601:surgery; D012016:Reference Values; D012720:Severity of Illness Index; D013585:Synovitis / Q000097:blood / Q000175:diagnosis / Q000209:etiology*
D015415:Biomarkers; D024042:Collagen Type I; D024043:Collagen Type II; D024061:Collagen Type III; D020782:Matrix Metalloproteinases
Biochemical markers of inflammation and collagen turnover; Inflammation; Matrix metalloproteinases; Osteoarthritis; Selection of the right patients for the right treatment