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T-cell restriction in thyroid eye disease

A E Heufelder1

  • 1Division of Endocrinology, Klinikum Innenstadt, Ludwig-Maximilians-University, München, Germany.

Thyroid : Official Journal of the American Thyroid Association
|June 12, 1998
PubMed
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In thyroid eye disease (TED), T cells in the eyes and skin show similar genetic markers, suggesting a shared autoimmune target. This indicates a potential common antigen driving inflammation in Graves’ disease (GD) with extrathyroidal manifestations.

Area of Science:

  • Immunology
  • Endocrinology
  • Ophthalmology

Background:

  • Thyroid eye disease (TED) involves immune cells attacking orbital tissues.
  • The specific antigens targeted by these T cells, especially in Graves' disease (GD) with extrathyroidal manifestations like pretibial dermopathy (PTD), remain unclear.
  • It's unknown if T cells in different affected tissues (thyroid, orbit, pretibial area) target shared antigens.

Purpose of the Study:

  • To investigate whether T cells infiltrating orbital tissues in TED are directed against specific orbital antigens.
  • To determine if T cells in the thyroid, orbit, and pretibial tissues of patients with GD, TED, and PTD target shared antigenic determinants.
  • To analyze the T-cell receptor (TcR) gene usage in different affected tissues to understand the immune response.

Main Methods:

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  • Polymerase chain reaction (PCR)-based molecular analysis of T-cell antigen receptor (TcR) variable (V) region genes.
  • Analysis of TcR V genes in orbital connective/fatty tissue, extraocular muscles, thyroid gland, pretibial tissue, and peripheral blood.
  • Sequencing of complementarity determining regions 3 (CDR3) and junctional domains of TcR Vbeta genes.

Main Results:

  • Marked restriction of TcR Valpha and Vbeta genes was observed in orbital and pretibial tissues of patients with active TED and PTD.
  • Similar TcR V gene usage was found in paired samples of extraocular muscle and orbital connective/fatty tissue.
  • TcR gene restriction was less pronounced in patients with longstanding TED and PTD.
  • Comparison of TcR V genes across thyroid, orbital, pretibial tissues, and peripheral blood revealed marked restriction and similarities in active GD, TED, and PTD.
  • Sequencing confirmed T-cell oligoclonality and identified conserved junctional motifs shared between thyroid and extrathyroidal infiltrating T cells.

Conclusions:

  • The data suggest that similar antigenic determinants may be responsible for the recruitment and oligoclonal expansion of T cells in both the thyroid gland and extrathyroidal sites in patients with GD and extrathyroidal manifestations.
  • This implies a common autoimmune basis for the diverse clinical presentations of Graves' disease.
  • Further research into these shared antigens could lead to targeted therapies for TED and related conditions.