Transforming growth factor beta-1 and gene polymorphisms in oriental ankylosing spondylitis

Abstract

Objectives. To study serum levels of transforming growth factor beta-1 (TGFβ1) and the expression of TGFβ1 in in vitro peripheral blood mononuclear cell (PBMC) cultures in oriental ankylosing spondylitis (AS) patients, and to determine their association with codon 10 and 25 TGFB1 gene polymorphisms. Methods. Serum levels of TGFβ1 were measured by enzyme-linked immunosorbent assay (ELISA). The ability of PBMCs to synthesize TGFβ 1 and other cytokines was assessed by in vitro cultures stimulated with mitogen. Genomic DNA was extracted from PBMCs of AS patients (n = 72) or unrelated healthy controls (n = 96). The codon 10 and 25 polymorphisms in the TGFB1 gene were analysed using standard polymerase chain reaction-based methods. Results. AS patients had significantly higher serum TGFβ1 levels than controls (P<0.001). There was no difference in the distribution of codon 10 and 25 TGFB1 genotypes between AS patients and controls. Incubation of AS and control PBMC with phytohaemagglutinin (PHA) led to upregulation of TGFP1, interleukin-10, tumour necrosis factor-alpha (TNFα) and interferon-γ (IFNγ) assessed by ELISA. Importantly, PHA-induced TGFβ1 production was significantly enhanced in AS patients compared with normal controls whereas the production of the pro-inflammatory cytokines TNFα and IFNγ was reduced. Conclusions. Our results show that AS patients express significantly higher levels of serum TGFβ1 independent of the codon 10 and 25 genotype. Activation of AS PBMCs led to enhanced TGFβ1 production accompanied by reduction of TNFα and IFNγ while the converse was observed in normal controls. © British Society for Rheumatology 2004; all rights reserved.