title: Follistatin-like protein 1 is elevated in systemic autoimmune diseases and correlated with disease activity in patients with rheumatoid arthritis.
abstract: BACKGROUND
  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.
authors.affiliation: 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. ldw20319750826@hotmail.com
authors.forename: Dawei
authors.initials: D
authors.lastname: Li
authors.forename: Yuji
authors.initials: Y
authors.lastname: Wang
authors.forename: Nanwei
authors.initials: N
authors.lastname: Xu
authors.forename: Qianghua
authors.initials: Q
authors.lastname: Wei
authors.forename: Min
authors.initials: M
authors.lastname: Wu
authors.forename: Xiaofeng
authors.initials: X
authors.lastname: Li
authors.forename: Ping
authors.initials: P
authors.lastname: Zheng
authors.forename: Sai
authors.initials: S
authors.lastname: Sun
authors.forename: Yuli
authors.initials: Y
authors.lastname: Jin
authors.forename: Gailian
authors.initials: G
authors.lastname: Zhang
authors.forename: Ruomin
authors.initials: R
authors.lastname: Liao
authors.forename: Ping
authors.initials: P
authors.lastname: Zhang
mesh_terms: D000328:Adult; D001172:Arthritis, Rheumatoid / Q000276:immunology* / Q000378:metabolism; D001327:Autoimmune Diseases / Q000276:immunology / Q000378:metabolism; D015415:Biomarkers / Q000032:analysis* / Q000378:metabolism; D015153:Blotting, Western; D004797:Enzyme-Linked Immunosorbent Assay; D005347:Fibroblasts / Q000276:immunology / Q000378:metabolism; D038702:Follistatin-Related Proteins / Q000032:analysis / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D008875:Middle Aged; D060888:Real-Time Polymerase Chain Reaction; D055815:Young Adult
chemical_list: D015415:Biomarkers; D038702:Follistatin-Related Proteins; C448799:FSTL1 protein, human