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

Wiley - Tập 54 Số 4 - Trang 1122-1131 - 2006
Bruce Kirkham1,2, Marissa Lassere3, John Edmonds3, Katherine M. Juhasz3, Paul Bird3, C. Soon Lee4, Ron Shnier3, Ian Portek3
1Department of Rheumatology, 4th Floor Thomas Guy House, Guy's Hospital, London SE1 9RT, UK
2Guy's and St Thomas' Hospital, London, UK
3St. George Hospital, Sydney, New South Wales, Australia
4Royal Prince Alfred Hospital, Sydney, New South Wales, Australia

Tóm tắt

AbstractObjectiveThe 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.MethodsPatients 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.ResultsSixty 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.ConclusionWe 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.

Từ khóa


Tài liệu tham khảo

10.1002/1529-0131(200109)44:9<2009::AID-ART349>3.0.CO;2-L

10.1002/1529-0131(199909)42:9<1854::AID-ANR9>3.0.CO;2-F

10.1002/art.1780270805

10.1002/1529-0131(199809)41:9<1571::AID-ART7>3.0.CO;2-R

10.1002/1529-0131(200012)43:12<2619::AID-ANR1>3.0.CO;2-V

10.1002/art.1780390116

10.1016/S0049-0172(96)80041-2

Katrib A, 2003, Reduced chemokine and matrix metalloproteinase expression in patients with rheumatoid arthritis achieving remission, J Rheumatol, 30, 10

10.1038/46303

10.1016/S0889-857X(03)00073-5

10.7326/0003-4819-130-6-199903160-00004

10.1093/rheumatology/40.11.1243

10.1136/ard.53.1.39

10.1186/ar79

10.1002/art.1780310302

Lassere M, 1997, Reference curves of radiographic damage in patients with rheumatoid arthritis: application of quantile regression and fractional polynomials, J Rheumatol, 24, 1288

10.1002/art.1780230202

10.1177/028418517701800415

Conaghan P, 2001, Magnetic resonance imaging in rheumatoid arthritis: summary of OMERACT activities, current status, and plans, J Rheumatol, 28, 1158

Edmonds J, 1999, Introduction to reading radiographs by the Scott modification of the Larsen method, J Rheumatol, 26, 740

Kirkham B, 1999, Intraarticular variability of synovial membrane histology, immunohistology, and cytokine mRNA expression in patients with rheumatoid arthritis, J Rheumatol, 26, 777

10.1002/art.1780310803

Klimiuk PA, 1997, Tissue cytokine patterns distinguish variants of rheumatoid synovitis, Am J Pathol, 151, 1311

StataCorp, 2001, Stata statistical software: release 7.0

Hamilton LC, 1991, How robust is robust regression?, Stata Technical Bulletin, 2, 21

Joosten LA, 1999, IL‐1α/β blockade prevents cartilage and bone destruction in murine type II collagen‐induced arthritis whereas TNF‐α blockade only ameliorates joint inflammation, J Immunol, 163, 5049, 10.4049/jimmunol.163.9.5049

10.1002/1529-0131(200106)44:6<1293::AID-ART221>3.0.CO;2-T

10.1084/jem.179.5.1517

10.1002/art.1780400209

10.1002/art.11160

10.1038/35046102

10.1046/j.1365-2249.2001.01469.x

Kumar V, 1998, Induction or protection from experimental autoimmune encephalomyelitis depends on the cytokine profile of TCR peptide‐specific regulatory CD4 T cells, J Immunol, 161, 6585, 10.4049/jimmunol.161.12.6585

10.1002/art.10556

10.1136/bmj.328.7441.702

10.1002/art.20165

Thông tin
Thông tin xuất bản

Wiley

Tập 54 Số 4

1122-1131

Thông tin tác giả