Synovial membrane cytokine expression is predictive of joint damage progression in rheumatoid arthritis: A two‐year prospective study (the DAMAGE study cohort)

Kirkham, Bruce W.; Lassere, Marissa N.; Edmonds, John P.; Juhasz, Katherine M.; Bird, Paul A.; Lee, C. Soon; Shnier, Ron; Portek, Ian J.

doi:10.1002/art.21749

Cited by 336Rheumatoid Arthritis Research and TherapiesAutoimmune and Inflammatory Disorders ResearchOsteoarthritis Treatment and Mechanisms

Synovial membrane cytokine expression is predictive of joint damage progression in rheumatoid arthritis: A two‐year prospective study (the DAMAGE study cohort)

Kirkham, Bruce W., Lassere, Marissa N., Edmonds, John P., Juhasz, Katherine M., Bird, Paul A., Lee, C. Soon, Shnier, Ron, Portek, Ian J.·2006·Arthritis & Rheumatism

DOI 10.1002/art.21749

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Abstract

Objective: The primary aim of this prospective 2‐year study was to explain the wide variability in joint damage progression in patients with rheumatoid arthritis (RA) from measures of pathologic changes in the synovial membrane. Methods: Patients underwent clinical measurements and joint damage assessments by magnetic resonance imaging (MRI) and radiography at enrollment and at year 2. Synovial membrane was obtained by knee biopsy and assessed histologically by hematoxylin and eosin staining. Interleukin‐1β (IL‐1β), IL‐10, IL‐16, IL‐17, RANKL, tumor necrosis factor α (TNFα), and interferon‐γ (IFNγ) messenger RNA (mRNA) expression was determined by quantitative reverse transcription–polymerase chain reaction. The relationship of synovial measurements to joint damage progression was determined by multivariate analysis. Results: Sixty patients were enrolled. Histologic features had no relationship to damage progression. Multivariate analysis by several different methods consistently demonstrated that synovial membrane mRNA levels of IL‐1β, TNFα, IL‐17, and IL‐10 were predictive of damage progression. IL‐17 was synergistic with TNFα. TNFα and IL‐17 effects were most pronounced with shorter disease duration, and IL‐1β effects were most pronounced with longer disease duration. IFNγ was protective. These factors explained 57% of the MRI joint damage progression over 2 years. Conclusion: We have demonstrated for the first time in a prospective study that synovial membrane cytokine mRNA expression is predictive of joint damage progression in RA. The findings for IL‐1β and TNFα are consistent with results of previous clinical research, but the protective role of IFNγ, the differing effects of disease duration, and IL‐17–cytokine interactions had only been demonstrated previously by animal and in vitro research. These findings explain some of the variability of joint damage in RA and identify new targets for therapy.

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“the transfer of in vitro differentiated pathogenic Th17 cells expressing a transgenic TCR specific for the MOG35–55 peptide (2D2 cells [114]) is sufficient to induce severe disease in recipient mice”
From TH17 cell heterogeneity and its role in tissue inflammation (2023) · cites this paper as [115]

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Authors: Kirkham, B. W., Lassere, M. N., Edmonds, J. P., Juhasz, K. M., Bird, P. A., Lee, C. S., Shnier, R., & Portek, I. J.
Affiliations: Guy's Hospital (GB)
St George Hospital (AU)
Royal Prince Alfred Hospital (AU)
ORCID: Kirkham, Bruce W.
Bird, Paul A.
Venue: Arthritis & Rheumatism
Publisher: Wiley
Published: 2006-03-29
Volume: 54
Issue: 4
Pages: 1122-1131
ISSN: 0004-3591 (ISSN-L)
1529-0131
DOI: 10.1002/art.21749
OpenAlex: W2014830732
Cited by: 336
References: 40
Citations by year: 2025: 7 · 2024: 4 · 2023: 9 · 2022: 10 · 2021: 7 · 2020: 8 · 2019: 16 · 2018: 11 · 2017: 15 · 2016: 21 · 2015: 20 · 2014: 18 · 2013: 22 · 2012: 29
FWCI: 14.50
Type: journal article
Language: en
Open access: closed
Licence: onlinelibrary.wiley.com/termsAndConditions#vor (vor)
Locations: Arthritis & Rheumatism (publishedVersion)
PubMed (publishedVersion)
Topics: Health Sciences › Medicine › Rheumatology › Rheumatoid Arthritis Research and Therapies
Health Sciences › Medicine › Hematology › Autoimmune and Inflammatory Disorders Research
Health Sciences › Medicine › Rheumatology › Osteoarthritis Treatment and Mechanisms
Keywords: rheumatoid arthritis, joint damage progression, synovium, cytokine mRNA expression, IL-1β, TNF-α, IL-17, IL-10, interferon-gamma, disease duration, synovial biopsy, predictive biomarkers
MeSH terms: Adult, Aged, Aged, 80 and over, Arthritis, Rheumatoid, Female, Humans, Magnetic Resonance Imaging, Male, Middle Aged, Prognosis, Prospective Studies, RNA, Messenger, Synovial Membrane, Time Factors, Cytokines, Disease Progression

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Synovial membrane cytokine expression is predictive of joint damage progression in rheumatoid arthritis: A two‐year prospective study (the DAMAGE study cohort)

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