Vol.22 No.1

Original Article

Abrogation of Treg function deteriorates rheumatoid arthritis

Authors

Tokuyoshi Yamagiwa1 , Shigeo Fukunishi1 , Toshiya Tachibana1 , Haruki Okamura2 , Shinichi Yoshiya1 , Shin-ichiro Kashiwamura3

  • Department of Orthopaedic Surgery, Hyogo College of Medicine, 1-1 Mukogawa-cho, Nishinomiya, Hyogo, 663-8501, Japan
  • Laboratory for Host Defense, Institute for Advanced Medical Sciences, Hyogo College of Medicine, Nishinomiya, Hyogo, 663-8501, Japan
  • Department of Biology, Hyogo College of Medicine, Nishinomiya, Hyogo, 663-8501, Japan
Received:

10 March 2011

Accepted:

16 May 2011

Published online:

14 June 2011

Full Text

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Abstract

An early prognostic indicator which warns of progressive joint destruction of rheumatoid arthritis (RA) was explored using a novel suspension-array technique in moderate (Steinbrocker stage I and II) and severe (Steinbrocker stage IV) RA patients. DNA microarray analysis of peripheral blood lymphocytes showed significant increase of interleukin (IL)-2 receptor α-chain (CD25) gene expression, a regulatory T cell (Treg) surface marker in severe RA patients. In contrast, suspension array, a comprehensive bead-based enzyme-linked immunosorbent assay (ELISA), revealed decreased production of IL-10 and increased production of interferon (IFN)-γ in sera in the incipient stage of the aggressive disease process. Both in moderate and in severe RA patients, the IFN-γ/IL-10 ratio indicated deterioration of the disease with universal validity. Fluorescence-activated cell sorting (FACS) and reverse-transcription polymerase chain reaction (RT-PCR) analysis showed extant CD4+CD25+ regulatory T cells in severe RA patients, however Foxp3, a regulatory T cellspecific transcription factor, gene expression was absent, while glucocorticoid-induced tumor necrosis factor (TNF) receptor family-related protein (GITR), which transmits a signal that abrogates regulatory T cell functions, was elevated. In the current study, we showed the validity of suspension-array analysis for enabling more complete understanding of RA, and showed that IFN-γ/IL-10 ratio can be a prognostic tool for early lesion and more aggressive RA.

Key words

Rheumatoid arthritis - Regulatory T cell - Glucocorticoid-induced TNF receptor family-related protein (GITR) - DNA microarray analysis - Suspensionarray analysis