Rheumatoid arthritis synovial fibroblasts produce a soluble form of the interleukin-7 receptor in response to pro-inflammatory cytokines

被引：38

作者：

Badot, V. ^{[1
,2
]}

Durez, P. ^{[1
]}

Van den Eynde, B. J. ^{[3
,4
]}

Nzeusseu-Toukap, A. ^{[1
]}

Houssiau, F. A. ^{[1
]}

Lauwerys, B. R. ^{[1
]}

机构：

[1] Catholic Univ Louvain, Clin Univ St Luc, Dept Rheumatol, B-1200 Brussels, Belgium

[2] CHU Brugmann, Dept Rheumatol, Brussels, Belgium

[3] De Duve Inst, Brussels, Belgium

[4] Ludwig Inst Canc Res, Brussels, Belgium

来源：

JOURNAL OF CELLULAR AND MOLECULAR MEDICINE | 2011年 / 15卷 / 11期

关键词：

rheumatoid arthritis; TNF blockade; biomarker; interleukin-7 receptor a-chain; ANTITUMOR NECROSIS FACTOR; MONOCLONAL-ANTIBODY; HUMAN PLASMA; DOUBLE-BLIND; ALPHA; METHOTREXATE; EXPRESSION; ADALIMUMAB; TRIAL; IDENTIFICATION;

D O I：

10.1111/j.1582-4934.2010.01228.x

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

We previously demonstrated that baseline synovial overexpression of the interleukin-7 receptor a-chain (IL-7R) is associated with poor response to tumour necrosis factor (TNF) blockade in rheumatoid arthritis (RA). We found that IL-7R gene expression is induced in fibroblast-like synovial cells (FLS) by the addition of TNF-a, IL-1 beta and combinations of TNF-a+ IL-1 beta or TNF-a+ IL-17, thereby suggesting that these cytokines play a role in the resistance to TNF blockade in RA. Because FLS and CD4 T cells also produce a soluble form of IL-7R (sIL-7R), resulting from an alternative splicing of the full-length transcript, we wondered whether expression of sIL-7R is similarly regulated by pro-inflammatory cytokines. We also investigated whether sIL-7R is detectable in the serum of RA patients and associated with response to TNF blockade. RA FLS were cultured in the presence of pro-inflammatory cytokines and sIL-7R concentrations were measured in culture supernatants. Similarly, sIL-7R titres were measured in sera obtained from healthy individuals, early untreated RA patients with active disease and disease-modifying anti-rheumatic drug (DMARD)-resistant RA patients prior to initiation of TNF-blockade. Baseline serum sIL-7R titres were correlated with validated clinical measurements of disease activity. We found that exposure of RA FLS to pro-inflammatory cytokines (TNF-a, IL-1 beta and combinations of TNF-a and IL-1 beta or TNF-a and IL-17) induces sIL-7R secretion. Activated CD4 T cells also produce sIL-7R. sIL-7R serum levels are higher in RA patients as compared to controls. In DMARD-resistant patients, high sIL-7R serum concentrations are strongly associated with poor response to TNF-blockade. In conclusion, sIL-7R is induced by pro-inflammatory cytokines in RA FLS. sIL-7R could qualify as a new biomarker of response to therapy in RA.

引用

页码：2335 / 2342

页数：8

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