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Open Access Research article

Follistatin-like protein 1 is elevated in systemic autoimmune diseases and correlated with disease activity in patients with rheumatoid arthritis

Dawei Li1*, Yuji Wang12*, Nanwei Xu2, Qianghua Wei3, Min Wu4, Xiaofeng Li5, Ping Zheng6, Sai Sun1, Yuli Jin3, Gailian Zhang5, Ruomin Liao7 and Ping Zhang8

Author Affiliations

1 State Key Laboratory of Genetic Engineering, Institute of Genetics, School of Life Sciences, Fudan University, 220 Handan Road, Shanghai, 200433, People's Republic of China

2 Department of Orthopaedics, the Affiliated Hospital of Nanjing Medical University, Changzhou second People's Hospital, 29 Xinglong Alley, Changzhou, 213003, People's Republic of China

3 Department of Rheumatology, Shanghai First People's Hospital Affiliated to Shanghai Jiaotong University, 85 Wujin Road, Shanghai, 200080, People's Republic of China

4 Department of Rheumatology and Immunology, The Third Affiliated Hospital, Suzhou University, Changzhou first People's Hospital, 185 Juqian Street, Changzhou, 213003, People's Republic of China

5 Department of Rheumatology, the Second Hospital, Shanxi Medical University, 382 Wuyi Road, Taiyuan, 030001, People's Republic of China

6 Department of Gastroenterology, Shanghai First People's Hospital Affiliated to Shanghai Jiaotong University, 85 Wujin Road, Shanghai, 200080, People's Republic of China

7 Department of Respiratory Medicine, Shanghai First People's Hospital Affiliated to Shanghai Jiaotong University, 85 Wujin Road, Shanghai, 200080, People's Republic of China

8 Clinical laboratory, the Affiliated Hospital of Nanjing Medical University, Changzhou Second People's Hospital, 29 Xinglong Alley, Changzhou, 213003, People's Republic of China

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Arthritis Research & Therapy 2011, 13:R17  doi:10.1186/ar3241

Published: 8 February 2011

Abstract

Introduction

Follistatin-like protein 1 (FSTL1) is a proinflammation mediator implicated in arthritis in rodent animal models. The present study is aimed at assessing FSTL1 levels in systemic autoimmune diseases and correlating them with disease activity in patients with rheumatoid arthritis (RA).

Methods

Serum FSTL1 levels from 487 patients with systemic autoimmune diseases and 69 healthy individuals were measured by enzyme-linked immunosorbent assay (ELISA). FSTL1 expression in synovial fluid (SF) and synovial tissues (STs) was determined by ELISA, immunohistochemistry, real-time polymerase chain reaction (RT-PCR) and western blot analysis in RA patients and trauma controls. FSTL1 levels in fibroblast-like synoviocytes (FLSs) from RA patients were determined by real-time PCR and western blot analysis.

Results

Serum FSTL1 levels were significantly elevated in patients with RA, ulcerative colitis, systemic lupus erythematosus, Sjögren's syndrome (SS), systemic sclerosis and polymyositis/dermatomyositis. Serum FSTL1 levels in the RA and secondary SS patients were substantially higher than those in other patients. Serum FSTL1 levels were increased in early RA, rheumatoid factor (RF)- and anti-cyclic citrullinated peptide antibody (ACPA)-negative patients compared to healthy controls. Moreover, serum FSTL1 concentrations were significantly higher in long-standing RA patients than in early RA patients and in the RF- and ACPA-positive RA patients than in RF- and ACPA-negative RA patients. Elevated FSTL1 levels in the STs and SF of RA patients were also observed. FSTL1 levels in serum were markedly higher than those in SF in RA patients. The strongest FSTL1 staining was detected in the cytoplasm of synovial and capillary endothelial cells from RA synovium. Furthermore, FSTL1 was induced in FLSs by inflammatory mediators. Importantly, serum FSTL1 levels were correlated with several important biologic and clinical markers of disease activity, including erythrocyte sedimentation rate, C-reactive protein, RF, ACPA, swollen joint count, patient global visual analogue scale score and Disease Activity Score 28 in the adult RA patient population. Notably, serum FSTL1 levels were significantly diminished following successful treatment and clinical improvement.

Conclusions

Elevated FSTL1 levels reflect not only joint diseases but also inflammation and tissue degradation in systemic autoimmune diseases. Serum FSTL1 levels may thus serve as a serological inflammatory marker of disease activity in RA patients.