Defective function of Fas in T cells from paediatric patients with autoimmune thyroid diseases

G. Bona, S. Defranco, A. Chiocchetti, M. Indelicato, A. Biava, D. Difranco, I. Dianzani, U. Ramenghi, A. Corrias, G. Weber, V. De Sanctis, L. Iughetti, G. Radetti, Umberto Dianzani

Research output: Contribution to journalArticle

21 Citations (Scopus)

Abstract

Triggering of the Fas receptor induces T cell apoptosis and is involved in shutting-off the immune response. Inherited defects impairing Fas function cause the autoimmune lymphoproliferative syndrome, and may play a role in other autoimmune diseases. The aim of this work was to analyse the Fas function in paediatric patients with thyroid autoimmunities. We found that T cells from 24/28 patients with Graves' disease (GD) and 12/35 patients with Hashimoto's thyroiditis (HT) displayed defective Fas function. In HT, the defect was more frequent in patients requiring replacement therapy (11/20) than in those not requiring (1/15); moreover, in untreated HT the highest defect was displayed by patients with the highest levels of autoantibodies. Fas was always expressed at normal levels and no Fas mutations were detected. Analysis of the healthy parents of seven Fas-resistant patients showed that several of them were Fas-resistant, which suggests a genetic component. Fusion of Fas-resistant T cells with the Fas-sensitive HUT78 T cell line generated Fas-resistant hybrid cells, which suggests the presence of molecules exerting a dominant negative effect on Fas function. Analysis of Fas-induced activation of caspase-8 and -9 showed decreased activity of both caspases in HT, whereas activity of caspase-9 was increased and that of caspase-8 was decreased in GD. These data suggest that heterogeneous inherited defects impairing Fas function favour the development of thyroid autoimmunities.

Original languageEnglish
Pages (from-to)430-437
Number of pages8
JournalClinical and Experimental Immunology
Volume133
Issue number3
DOIs
Publication statusPublished - Sep 1 2003

Fingerprint

Thyroid Diseases
Autoimmune Diseases
Hashimoto Disease
Pediatrics
T-Lymphocytes
Caspase 9
Caspase 8
Graves Disease
Autoimmunity
Thyroid Gland
Autoimmune Lymphoproliferative Syndrome
CD95 Antigens
Hybrid Cells
Caspases
Autoantibodies
Parents
Apoptosis
Cell Line
Mutation

Keywords

  • Apoptosis
  • CD95
  • Fas
  • T cell

ASJC Scopus subject areas

  • Immunology

Cite this

Bona, G., Defranco, S., Chiocchetti, A., Indelicato, M., Biava, A., Difranco, D., ... Dianzani, U. (2003). Defective function of Fas in T cells from paediatric patients with autoimmune thyroid diseases. Clinical and Experimental Immunology, 133(3), 430-437. https://doi.org/10.1046/j.1365-2249.2003.02221.x

Defective function of Fas in T cells from paediatric patients with autoimmune thyroid diseases. / Bona, G.; Defranco, S.; Chiocchetti, A.; Indelicato, M.; Biava, A.; Difranco, D.; Dianzani, I.; Ramenghi, U.; Corrias, A.; Weber, G.; De Sanctis, V.; Iughetti, L.; Radetti, G.; Dianzani, Umberto.

In: Clinical and Experimental Immunology, Vol. 133, No. 3, 01.09.2003, p. 430-437.

Research output: Contribution to journalArticle

Bona, G, Defranco, S, Chiocchetti, A, Indelicato, M, Biava, A, Difranco, D, Dianzani, I, Ramenghi, U, Corrias, A, Weber, G, De Sanctis, V, Iughetti, L, Radetti, G & Dianzani, U 2003, 'Defective function of Fas in T cells from paediatric patients with autoimmune thyroid diseases', Clinical and Experimental Immunology, vol. 133, no. 3, pp. 430-437. https://doi.org/10.1046/j.1365-2249.2003.02221.x
Bona, G. ; Defranco, S. ; Chiocchetti, A. ; Indelicato, M. ; Biava, A. ; Difranco, D. ; Dianzani, I. ; Ramenghi, U. ; Corrias, A. ; Weber, G. ; De Sanctis, V. ; Iughetti, L. ; Radetti, G. ; Dianzani, Umberto. / Defective function of Fas in T cells from paediatric patients with autoimmune thyroid diseases. In: Clinical and Experimental Immunology. 2003 ; Vol. 133, No. 3. pp. 430-437.
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