- Paper Report
- Open Access
Graves' disease immunoglobulins induce expression of T-cell chemoattractants in fibroblasts
- Elena Neumann1
© Biomed Central Ltd 2002
- Received: 4 February 2002
- Accepted: 5 February 2002
- Published: 8 February 2002
- fibroblast activation
- Graves' disease
Graves' disease (GD) is an autoimmune disease of the thyroid gland. Extrathyroidal manifestations of GD include ophthalmopathy and dermopathy, which are characterised by infiltration of inflammatory cells such as T lymphocytes and accumulation of hyaluronan. Infiltration and activation of T cells are most likely mediated by chemokines and T-cell activators, however, the mechanisms by which immunocompetent cells traffic to affected tissues in GD and by which fibroblasts are activated are still unknown. Similar to the situation in rheumatoid arthritis, it is hypothesised that inflammatory mediators play an important role in fibroblast activation at the sites of disease manifestation. A self-antigen expressed only at the sites of GD manifestations could account for the distribution of GD leading directly to the activation of fibroblasts followed by production of chemoattractants and activators of inflammatory cells. Moreover, some reports have suggested direct effects of IgG isolated from patients with GD (GD-IgG) on human fibroblasts. Therefore, the authors investigated whether IgG from patients with GD activate the expression and release of T-cell chemoattractants such as IL-16 and RANTES from fibroblasts.
GD-IgG upregulated T-cell chemoattractant activity in fibroblasts from the thyroid gland and from areas with extrathyroidal GD manifestations, but not in fibroblasts from donors without thyroid disease. The protein levels of IL-16 and RANTES were increased by GD-IgG in GD fibroblasts from the affected regions. T-cell migration could be partially reduced by neutralisation with anti-IL-16 and anti-RANTES antibodies. The authors excluded GD-IgG induced T-cell chemoattractant activity by ligation of the key autoantigen, thyroid-stimulating hormone receptor (TSHR). It is concluded that autoantibodies present in the IgG fraction from patients with GD induce T-cell chemoattractant activity in fibroblasts from patients with GD through a yet unknown antigen.
Chemotaxis assay, IgG preparation, immunoprecipitation, western blot analysis
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