Osteoprotegerin and tumor necrosis factor-related apoptosis-inducing ligand as prognostic factors in rheumatoid arthritis: results from the ESPOIR cohort

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Abstract

Introduction

We previously reported that low ratio of osteoprotegerin (OPG) to tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) was associated with Disease Activity Score in 28 joints (DAS28) remission at 6 months in patients with early rheumatoid arthritis (RA). Here, we aimed to evaluate the value of baseline OPG/TRAIL ratio in predicting clinical and radiological outcomes in patients with early RA in the ESPOIR cohort.

Methods

OPG and TRAIL serum concentrations were assessed in the ESPOIR cohort patients. Patients with definite RA were included in this study. Patients were excluded if they had high erosion score at baseline (>90 ^th percentile) or received biological therapy during the first 2 years of follow-up. Data were analyzed by univariate analysis and multivariate logistic regression to predict 1-year DAS28 remission and 2-year radiographic disease progression.

Results

On univariate analysis of 399 patients, OPG/TRAIL ratio at baseline was significantly lower in patients with than without remission at 1 year ( p = 0.015). On multivariate logistic regression including age, gender, body mass index and DAS28, low OPG/TRAIL ratio was independently associated with remission at 1 year (odds ratio 1.68 [95 % confidence interval 1.01–2.79]). On univariate analysis, high OPG/TRAIL ratio at baseline was associated with rapid progression of erosion at 2 years ( p = 0.041), and on multivariate logistic regression including age, anti-citrullinated protein antibody positivity and C-reactive protein level, OPG/TRAIL ratio independently predicted rapid progression of erosion at 2 years.

Conclusions

OPG/TRAIL ratio at baseline was an independent predictor of 1-year remission and 2-year rapid progression of erosion for patients with early rheumatoid arthritis. Thus, OPG/TRAIL ratio could be included in matrix prediction scores to predict rapid radiographic progression. Further confirmation in an independent cohort is warranted.

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Most cited references 22

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Anticitrullinated protein/peptide antibody assays in early rheumatoid arthritis for predicting five year radiographic damage.

O. Meyer, C Labarre, M Dougados … (2003)

To study the value of antibodies to citrullinated proteins/peptides for predicting joint outcomes in patients with recent onset rheumatoid arthritis (RA). 191 patients with RA onset within the past year were followed up prospectively for five years. Serum samples obtained from 145 patients at baseline before disease modifying antirheumatic drug treatment were examined using three anticitrullinated protein/peptide antibody assays: antiperinuclear factor (APF) by indirect immunofluorescence (IIF), antikeratin antibodies (AKA) by IIF, and anti-cyclic citrullinated peptide (CCP) antibodies by enzyme linked immunosorbent assay (ELISA). Radiographs of the hands and feet taken at baseline and after three and five years were evaluated using Sharp scores modified by van der Heijde. Anti-CCP ELISA was positive in 58.9% of patients. APF/anti-CCP agreement was 77%. The likelihood of a total Sharp score increase after five years was significantly greater among patients with anti-CCP antibodies (67%; odds ratio (OR) 2.5; 95% confidence interval (95% CI) 1.2 to 5.0) or APF (57%; OR 2.4; 95% CI 1.2 to 4.9) but not rheumatoid factor (RF; OR 0.7; 95% CI 0.3 to 1.5). Mean values for radiographic damage, erosion, and joint narrowing scores at the three times were significantly higher in patients with anti-CCP or APF than in those without. AKA did not significantly predict radiographic damage. In separate analyses of patients with and without RF, anti-CCP or APF was better than RF for predicting total joint damage and joint damage progression after five years. Antibodies to citrullinated proteins/peptides determined early in the course of RA by APF IIF or anti-CCP ELISA are good predictors of radiographic joint damage. Further studies of clinical, laboratory, and genetic parameters are needed to improve RA outcome prediction in clinical practice.

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A new member of tumor necrosis factor ligand family, ODF/OPGL/TRANCE/RANKL, regulates osteoclast differentiation and function.

N Takahashi, N Udagawa, T Suda (1999)

Osteoclasts, the multinucleated giant cells that resorb bone, develop from monocyte-macrophage lineage cells. Osteoblasts or bone marrow stromal cells have been suggested to be involved in osteoclastic bone resorption. The recent discovery of new members of the tumor necrosis factor (TNF) receptor-ligand family has elucidated the precise mechanism by which osteoblasts/stromal cells regulate osteoclast differentiation and function. Osteoblasts/stromal cells express a new member of the TNF-ligand family "osteoclast differentiation factor(ODF)/osteoprotegerin ligand (OPGL)/TNF-related activation-induced cytokine (TRANCE)/receptor activator of NF-kB ligand (RANKL)" as a membrane associated factor. Osteoclast precursors which possess RANK, a TNF receptor family member, recognize ODF/OPGL/TRANCE/RANKL through cell-to-cell interaction with osteoblasts/stromal cells, and differentiate into osteoclasts in the presence of macrophage colony-stimulating factor. Mature osteoclasts also express RANK, and their bone-resorbingactivity is also induced by ODF/OPGL/TRANCE/RANKL which osteoblasts/stromal cells possess. Osteoprotegerin (OPG)/osteoclastogenesis inhibitory factor (OCIF)/TNF receptor-like molecule 1 (TR1) is a soluble decoy receptor for ODF/OPGL/TRANCE/RANKL. Activation of NF-kB and c-Jun N-terminal kinase through the RANK-mediated signaling system appears to be involved in differentiation and activation of osteoclasts. Copyright 1999 Academic Press.

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Radiographic progression on radiographs of hands and feet during the first 3 years of rheumatoid arthritis measured according to Sharp's method (van der Heijde modification).

D van der Heijde, M A van Leeuwen, P. van Riel … (1995)

To determine the development rate of erosions and joint space narrowing in a cohort of patients during the first 3 years of rheumatoid arthritis (RA). All consecutive patients fulfilling the American Rheumatism Association criteria and seen within the 1st year of the disease were followed prospectively with biannual radiographs of hands and feet. One hundred and forty-seven patients were followed for 2 years and 90 patients for 3 years. Erosions and joint space narrowing were scored with a modified version of Sharp's method (van der Heijde modification). Wilcoxon's rank sum test was used to test differences between joints and between erosions and joint space narrowing. On average, at 3 year followup most groups of joints showed about 8% of the maximum possible score. In most groups of joints about 20% of the joints were affected. At the start more foot joints were affected than hand joints. However, the increase in the number of affected joints and in the radiographic damage was similar in hands and feet. Consequently, the predominance of affected foot joints was still present after 3 years. The progression in the 3rd year was statistically significantly less compared to the 1st year. This was more pronounced for the number of affected joints than for radiographic damage. We found that 70% of the patients showed radiographic damage after 3 years and this group could already be selected after 1 year. Overall, +/- 18-20% of the joints were affected after 3 years, with relatively few abnormalities per joint (+/- 8% of the maximum possible score was reached). The rate of progression in the 1st year was significantly more than in the 2nd and 3rd years, indicating a flattening of the curve of radiographic progression.

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Author and article information

Contributors

Rachel Audo: rachel.audo@igmm.cnrs.fr

Claire Daien: c-daien@chu-montpellier.fr

Laura Papon: laura.papon@igmm.cnrs.fr

Cédric Lukas: c-lukas@chu-montpellier.fr

Olivier Vittecoq: olivier.vittecoq@univ-rouen.fr

Michael Hahne: Michael.hahne@igmm.cnrs.fr

Bernard Combe: b-combe@chu-montpellier.fr

Jacques Morel: j-morel@chu-montpellier.fr

Journal

Journal ID (nlm-ta): Arthritis Res Ther

Title: Arthritis Research & Therapy

Publisher: BioMed Central (London )

ISSN (Print): 1478-6354

ISSN (Electronic): 1478-6362

Publication date (Electronic): 29 July 2015

Publication date PMC-release: 29 July 2015

Publication date (Print): 2015

Volume: 17

Issue: 1

Electronic Location Identifier: 193

Affiliations

[ ]Department of Rheumatology, Lapeyronie Hospital, Montpellier University, 371 avenue doyen Giraud, 34295 Montpellier, France

[ ]Montpellier University, 163 rue Auguste Broussonnet, 34000 Montpellier, France

[ ]Institut de Génétique Moléculaire de Montpellier, CNRS-UMR 5535, 1919 Route de Mende, 34293 Montpellier, France

[ ]Department of Rheumatology and CIC/CRB 1404, Rouen University Hospital, Inserm U 905, Institute for Research and Innovation in Biomedicine, 1, rue de Germont, 76031 Rouen, France

[ ]Academic Medical Center, University of Amsterdam, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands

Article

Publisher ID: 705

DOI: 10.1186/s13075-015-0705-3

PMC ID: 4518710

SO-VID: 60acf4b0-3f82-4eff-a9f2-33a08dcb26da

License:

This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

History

Date received : 27 January 2015

Date accepted : 2 July 2015

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ScienceOpen disciplines: Orthopedics

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ScienceOpen disciplines: Orthopedics

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Osteoprotegerin and tumor necrosis factor-related apoptosis-inducing ligand as prognostic factors in rheumatoid arthritis: results from the ESPOIR cohort

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Abstract

Introduction

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Orthopedics

Most cited references 22

Anticitrullinated protein/peptide antibody assays in early rheumatoid arthritis for predicting five year radiographic damage.

A new member of tumor necrosis factor ligand family, ODF/OPGL/TRANCE/RANKL, regulates osteoclast differentiation and function.

Radiographic progression on radiographs of hands and feet during the first 3 years of rheumatoid arthritis measured according to Sharp's method (van der Heijde modification).

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