The value of synovial cytokine expression in predicting the clinical response to TNF antagonist therapy (infliximab)

被引:30
作者
Buch, M. H. [1 ]
Reece, R. J. [1 ]
Quinn, M. A. [1 ]
English, A. [1 ]
Cunnane, G. [1 ]
Henshaw, K. [1 ]
Bingham, S. J. [1 ]
Bejarano, V. [1 ]
Isaacs, J. [1 ]
Emery, P. [1 ]
机构
[1] Univ Leeds, Acad Unit Musculoskeletal Dis, Leeds, W Yorkshire, England
关键词
rheumatoid arthritis; infliximab; synovial biopsy; tumour necrosis factor; cytokine;
D O I
10.1093/rheumatology/ken261
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Objectives. Clinical response to TNF-alpha blockade in the treatment of RA is heterogeneous. The study aims were to determine whether pre-treatment synovial cytokine expression predicted infliximab response and whether synovial changes after therapy correlated with response. Methods. Fifty-one patients had arthroscopic biopsies of the knee joint prior to infliximab (3 mg/kg) treatment. Synovial tissue cell numbers (CD68 and CD3 positive) and cytokine expression (TNF-alpha, lymphotoxin-alpha, IL-1 alpha, -beta and receptor antagonist, and IL-6) pre-treatment was assessed using semi-quantitative immunohistochemistry. Changes in these parameters were assessed 16 weeks after infliximab in 32 patients who underwent repeat arthroscopic biopsy. Results. Of the total patients, 47 (n = 24) achieved an ACR20 response; 53 (n = 27) did not. Baseline synovial TNF-alpha, IL-1 alpha and -beta expression did not differ between the two groups. No differences in baseline TNF-alpha levels were observed with ACR levels of response (ACR20 and ACR50/70 groups). Post-treatment biopsies (17 ACR responders, 15 ACR non-responders) revealed significant reductions in sub-lining layer TNF-alpha expression in both response and non-response groups with significant reduction in vascularity and membrane proliferation scores. The worst ACR non-responders (<20% CRP suppression) demonstrated no reduction in any of the parameters. Conclusion. Pre-treatment synovial TNF-alpha or IL-1 expression does not predict TNF blockade response. Both ACR response and non-response was associated with reduction in synovial TNF-alpha-level expression. Suppression in TNF-alpha levels was not observed in the worst non-responders. The improvements (including in vascularity), independent of ACR clinical response, are compatible with the reduced structural damage documented in all groups of patients independent of response.
引用
收藏
页码:1469 / 1475
页数:7
相关论文
共 22 条
[1]   THE AMERICAN-RHEUMATISM-ASSOCIATION 1987 REVISED CRITERIA FOR THE CLASSIFICATION OF RHEUMATOID-ARTHRITIS [J].
ARNETT, FC ;
EDWORTHY, SM ;
BLOCH, DA ;
MCSHANE, DJ ;
FRIES, JF ;
COOPER, NS ;
HEALEY, LA ;
KAPLAN, SR ;
LIANG, MH ;
LUTHRA, HS ;
MEDSGER, TA ;
MITCHELL, DM ;
NEUSTADT, DH ;
PINALS, RS ;
SCHALLER, JG ;
SHARP, JT ;
WILDER, RL ;
HUNDER, GG .
ARTHRITIS AND RHEUMATISM, 1988, 31 (03) :315-324
[2]   Effects of treatment with a fully human anti-tumour necrosis factor α monoclonal antibody on the local and systemic homeostasis of interleukin 1 and TNFα in patients with rheumatoid arthritis [J].
Barrera, P ;
Joosten, LAB ;
den Broeder, AA ;
van de Putte, LBA ;
van Riel, PLCM ;
van den Berg, WB .
ANNALS OF THE RHEUMATIC DISEASES, 2001, 60 (07) :660-669
[3]  
BRENNAN FM, 1989, LANCET, V2, P244
[4]  
*BRIT SOC RHEUM, 2001, WHO COLL CTR CONS M
[5]   C-reactive protein as a predictor of infliximab treatment outcome in patients with rheumatoid arthritis - Defining subtypes of nonresponse and subsequent response to etanercept [J].
Buch, MH ;
Seto, Y ;
Bingham, SJ ;
Bejarano, V ;
Bryer, D ;
White, J ;
Emery, P .
ARTHRITIS AND RHEUMATISM, 2005, 52 (01) :42-48
[6]   True infliximab resistance in rheumatoid arthritis:: a role for lymphotoxin α? [J].
Buch, MH ;
Conaghan, PG ;
Quinn, MA ;
Bingham, SJ ;
Veale, D ;
Emery, P .
ANNALS OF THE RHEUMATIC DISEASES, 2004, 63 (10) :1344-1346
[7]   Lack of response to anakinra in rheumatoid arthritis following failure of tumor necrosis factor α blockade [J].
Buch, MH ;
Bingham, SJ ;
Seto, Y ;
McGonagle, D ;
Bejarano, V ;
White, J ;
Emery, P .
ARTHRITIS AND RHEUMATISM, 2004, 50 (03) :725-728
[8]   Role of cytokines in rheumatoid arthritis [J].
Feldmann, M ;
Brennan, FM ;
Maini, RN .
ANNUAL REVIEW OF IMMUNOLOGY, 1996, 14 :397-440
[9]   Synovial tissue macrophages: a sensitive biomarker for response to treatment in patients with rheumatoid arthritis [J].
Haringman, JJ ;
Gerlag, DM ;
Zwinderman, AH ;
Smeets, TJM ;
Kraan, MC ;
Baeten, D ;
McInnes, IB ;
Bresnihan, B ;
Tak, PP .
ANNALS OF THE RHEUMATIC DISEASES, 2005, 64 (06) :834-838
[10]  
Klimiuk PA, 1997, AM J PATHOL, V151, P1311