Soluble CTLA-4 in autoimmune thyroid diseases: Relationship with clinical status and possible role in the immune response dysregulation

• Published in: Clinical Immunology 2007-05, Vol.123 (2), p.190-198
• Main Authors: Saverino, Daniele, Brizzolara, Renata, Simone, Rita, Chiappori, Alessandra, Milintenda-Floriani, Francesca, Pesce, Giampaola, Bagnasco, Marcello
• Format: Article
• Language: English
• Subjects: Adult; Allergy and Immunology; Antigens, CD - blood; Antigens, CD - metabolism; Antigens, CD - pharmacology; Antigens, Differentiation - blood; Antigens, Differentiation - metabolism; Antigens, Differentiation - pharmacology; Autoimmune Diseases - blood; Autoimmune Diseases - immunology; Autoimmune Diseases - metabolism; Autoimmunity; B-Lymphocytes - metabolism; B7-1 Antigen - metabolism; B7-2 Antigen - metabolism; Biological and medical sciences; CD28 Antigens - blood; Cell Line, Transformed; Cell Proliferation - drug effects; CTLA-4; CTLA-4 Antigen; Dose-Response Relationship, Drug; Female; Fundamental and applied biological sciences. Psychology; Fundamental immunology; Graves Disease - blood; Graves Disease - immunology; Graves Disease - metabolism; Hashimoto Disease - blood; Hashimoto Disease - immunology; Hashimoto Disease - metabolism; Humans; Immunopathology; Lymphocyte Activation - drug effects; Lymphocyte Activation - immunology; Lymphocyte Culture Test, Mixed; Male; Medical sciences; Middle Aged; Models, Immunological; Protein Binding; T-Lymphocytes - drug effects; T-Lymphocytes - immunology; Thyroid disease; Thyroid Diseases - blood; Thyroid Diseases - immunology; Thyroid Diseases - metabolism; Thyrotoxicosis - blood; Time Factors
• ISSN: 1521-6616; 1521-7035; 1365-2567
• DOI: 10.1016/j.clim.2007.01.003

Abstract CTLA-4 molecule, expressed by activated T and B lymphocytes, transduces an inhibitory signal. Increasing evidence showed CTLA-4 gene as an important susceptibility locus for autoimmune endocrinopathies and other autoimmune disorders. The aim is to evaluate the augmented sCTLA-4 serum levels in different autoimmune thyroid diseases when compared with normal donors or with non-autoimmune hyperthyroidism and to investigate the functional activities and suggest the possible pathogenetic role of sCTLA-4. We demonstrate the presence of a soluble form of CTLA-4 in 59/90 sera from patients with autoimmune thyroid diseases (both Graves’ disease and autoimmune thyroiditis). sCTLA-4 levels were not related to specific clinical manifestations, such as clinical thyroid status (hypo- or hyperthyroidism), circulating thyroid hormones, or other clinical features (ophthalmopathy). sCTLA-4 production does not seem to be affected by disease evolution during time. We showed that sCTLA-4 from sera of patients with thyroid autoimmunity is able to bind its physiological ligands CD80/CD86 and displays functional activities on different in vitro systems (T-cell proliferation induced by specific soluble antigens, bi-directional mixed lymphocyte reaction). In conclusion, we demonstrate an increment of sCTLA-4 in serum of patients with autoimmune thyroid diseases. Its possible pathogenetic role during autoimmune processes can be speculated: sCTLA-4 can specifically inhibit the early T-cell activation by blocking the interaction of CD80/CD86 with the co-stimulatory receptor CD28. Conversely, higher levels of sCTLA-4 could compete with membrane-bound CTLA-4 for CD80/CD86, in later T lymphocytes activation phase, causing a reduction of inhibitory signaling.