ACR Meeting Abstracts

ACR Meeting Abstracts

Abstract Number: 217

Circulating Levels of Neo-Epitopes Reflecting Connective Tissue Turnover As Biomarkers of Gout and Frequent Gout Attacks in Men

Ana Valdes1, Tina Manon-Jensen2, Wendy Jenkins3, Anne Sofie Siebuhr4, Morten Asser Karsdal4, Sally Doherty5, Abhishek Abhishek3, Helen Richardson3, Weiya Zhang6, Michael Doherty7 and Anne C. Bay-Jensen8, 1Division of Rheumatology, Orthopaedics and Dermatology, University of Nottingham, Nottingham, United Kingdom, 2Antibody Research Unit, Nordic Bioscience, 2370, Denmark, 3Devision of Rheumatology, University of Nottingham, NG5 1PB, England, 4Biomarkers and Research, Nordic Bioscience, Herlev, Denmark, 5Division of ROD, University of Nottingham, Nottingham, United Kingdom, 6Academic Rheumatology, School of Clinical Sciences, University of Nottingham, Nottingham, United Kingdom, 7Academic Rheumatology, City Hospital, Nottingham, United Kingdom, 8Biomarkers and Research, Rheumatology, Nordic Bioscience, Herlev, Denmark

Meeting: 2015 ACR/ARHP Annual Meeting

Date of first publication: September 29, 2015

Keywords: , ,

Session Information

Date: Sunday, November 8, 2015

Title: Metabolic and Crystal Arthropathies Poster I

Session Type: ACR Poster Session A

Session Time: 9:00AM-11:00AM

Background/Purpose: Recurrent flares constitute
the main clinical burden of gout. The neo-epitope blood-based biomarkers, C1M
and C3M, measuring matrix metalloproteinases (MMP)-mediated connective
tissue degradation, have previously been shown to be associated with
joint inflammation in rheumatoid arthritis and osteoarthritis. The aim of
present study was to evaluate the level of C1M and C3M in gout patients
compared to matched controls, to  investigate the discriminating power of these biomarkers
for frequent gout flares.

Methods: Fasting plasma
samples from 112 men with gout and 170 age-sex matched controls men
without gout (case-control study), and baseline serum samples from 447 community-derived
men with gout (RCT) were analysed by ELISA for neo-epitopes from MMP
degradation of collagens type I (C1M) and type III (C3M). The log10 of
C1M and C3M levels were compared between cases and controls, and between gout
patients with three or more gout attacks in the past year (frequent gout
flares) and those with two or less attacks, giving the odds ratio (OR[95%-CI)
and area under the curve.  

Results: The blood levels of the C1M and C3M
were significantly associated with gout status in the case-control study:
OR=4.1  log10C1M, and OR=82.8 for
log10C3M (table). The level of C3M was associated with frequent gout flares; in
the case-control participants with an OR=34.4 and in the RCT participants with
an OR=5.2 after adjustment for age, BMI and age at first attack (table). C1M
was also significantly associated with frequent flares in the RCT participants with
OR=2.8. The combination of available clinical variables gives an area under the
curve (AUC) of 0.68 and 0.60 for frequent gout attacks in the case-control and RCT
groups using a receiver operating characteristic (ROC) analysis. The AUC values
increase to 0.74 [0.63-0.84] and 0.66 [0.61-0.71] with the inclusion of
log10C1M and log10C3M in the model.

Conclusion: C1M and C3M were strongly
associated with gout status in a case-control study in men and with frequent
gout flares in two independent groups of men with ongoing gout, suggesting that
increased connective tissue turnover predispose to frequent gout flares, and
that biomarkers of connective tissue turnover may aid in identifying people at
risk of frequent attacks of gout

Table. Association between connective tissue degradation neo-epitopes and gout and frequent gout flares, odds ratios [95% confidence intervals] and p-values are shown for each of the associations tested

case-control

RCT

Association with:

log10C1M

log10C3M

log10C1M

log10C3M

Gout

OR=4.10 [1.51  -11.1]

p <0.0056

OR=82.8 [9.9-695]

p <2.4 x 10-5

—

—

≥3 gout flares unadjusted

OR=5.19 [0.99-27.1]

p< 0.051

OR=56.9 [1.26-2564]

p<0.037

OR=2.88 [1.22-6.80]

p< 0.016

OR=6.51 [2.22-19.1]

p< 0.0006

≥3 gout flares adj. age, BMI, age at first attack

OR=4.96 [0.86-28.8]

p<0.074

34.3 [0.65-1803]

p<0.080

OR=2.83 [1.17-6.81]

p< 0.020

OR=5.21 [2.05-18.7]

p< 0.0012

≥3 gout flares adj. age, BMI, age at first attack, SUA, tophi, num sites with tophi

—

—

OR=2.70 [1.11-6.51]

p< 0.027

OR=5.21 [1.71-15.87]

p< 0.0036

Meta-analysis of both cohorts

≥3 gout flares adj. age, BMI, age at first attack

OR=3.11 [1.42-6.81]

p=0.0056

OR=6.70 [2.33-19.3]

p=0.00053

Disclosure: A. Valdes, None; T. Manon-Jensen, Nordic Bioscience, 3; W. Jenkins, None; A. S. Siebuhr, None; M. A. Karsdal, Nordic Bioscience Diagnostic, 1,Nordic Bioscience Diagnostic, 3; S. Doherty, None; A. Abhishek, None; H. Richardson, None; W. Zhang, None; M. Doherty, None; A. C. Bay-Jensen, Nordic Bioscience Diagnostic, 1,Nordic Bioscience Diagnostic, 3.

To cite this abstract in AMA style:

Valdes A, Manon-Jensen T, Jenkins W, Siebuhr AS, Karsdal MA, Doherty S, Abhishek A, Richardson H, Zhang W, Doherty M, Bay-Jensen AC. Circulating Levels of Neo-Epitopes Reflecting Connective Tissue Turnover As Biomarkers of Gout and Frequent Gout Attacks in Men [abstract]. Arthritis Rheumatol. 2015; 67 (suppl 10). https://acrabstracts.org/abstract/circulating-levels-of-neo-epitopes-reflecting-connective-tissue-turnover-as-biomarkers-of-gout-and-frequent-gout-attacks-in-men/. Accessed .

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