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

Saverino, Danièle; Brizzolara, R.; Simone, Rita; Chiappori, Alessandra; Milintenda-Floriani, Francesca; Pesce, Giampaola; Bagnasco, Marcello

doi:10.1016/j.clim.2007.01.003

Cited by 85 publications

(102 citation statements)

References 38 publications

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“…In contrast, 6 of 45 serum samples from healthy controls had detectable sCTLA-4 (from 0.1 to 36.1 ng/ml) [49]. In addition, we observed that 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).…”

Section: Sctla-4 and Autoimmune Diseasescontrasting

confidence: 56%

“…A sCTLA-4, namely a functional molecule with specific CD80 and CD86 binding ability, generated by alternatively spliced mRNA has been described [10,13,20,[49][50][51][52][53]. The mRNA encoding sCTLA-4 consists of three exons: exon 1 encoding the leader peptide, exon 2 the ligand-binding domain, and exon 4 the cytoplasmic tail, but it lacks exon 3 encoding the transmembrane domain [10,20,53].…”

Section: Soluble Form Of Ctla-4mentioning

confidence: 99%

“…Detectable levels of sCTLA-4 have been demonstrated in human serum by immunometric assays and western blot analysis [10,11,13,20,49,51,53,[55][56][57][58][59][60]. Recently, however, on the basis of mass spectrometry and biochemical evaluation, the possibility that at least some of the B7 binding material isolated from serum by means of CTLA4 antibodies is not a product of the CTLA4 gene has been considered [61].…”

Section: Soluble Form Of Ctla-4mentioning

confidence: 99%

“…Increased serum levels of sCTLA-4 have been reported in patients with several autoimmune diseases significantly more often than in healthy individuals [20, 33, 49-51, 60, 62]. Patients with GD [20,33,49], HT [20,49], MG [50], systemic lupus erythematosus [55], systemic sclerosis (SSc) [54], CD [51], autoimmune pancreatitis (AIP) [62] and spondyloarthropathies and RA [60] have been investigated. The first studies on sCTLA-4 serum levels in autoimmune disease were performed 10 years ago [20] in 17 patients with GD and 3 patients with HT.…”

Section: Sctla-4 and Autoimmune Diseasesmentioning

confidence: 99%

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The soluble CTLA-4 receptor and its role in autoimmune diseases: an update

Saverino

Simone

Bagnasco

et al. 2010

Autoimmun Highlights

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CTLA-4, initially described as a membranebound molecule, is a costimulatory receptor transducing a potent inhibitory signal. Increasing evidence shows the CTLA-4 gene to be an important susceptibility locus for autoimmune endocrinopathies and other autoimmune disorders. A soluble form of cytotoxic T-lymphocyte-associated antigen-4 (sCTLA-4) has been established and shown to possess CD80/CD86 binding activity and in vitro immunoregulatory functions. sCTLA-4 is generated by alternatively spliced mRNA. Whereas low levels of sCTLA-4 are detected in normal human serum, increased serum levels are observed in several autoimmune diseases (e.g. Graves’ disease, myasthenia gravis, systemic lupus erythematosus, type 1 diabetes, systemic sclerosis, coeliac disease, autoimmune pancreatitis and primary biliary cirrhosis). The biological significance of increased sCTLA-4 serum levels is not fully clarified yet. On the one hand, it can be envisaged that sCTLA-4 specifically inhibits early T-cell activation by blocking the interaction of CD80/CD86 with the costimulatory receptor CD28. On the other hand, higher levels of sCTLA-4 could compete for the binding of the membrane form of CTLA-4 with CD80/CD86 in the later phases of T-lymphocyte activation, causing a reduction in inhibitory signalling. This double-edged nature of sCTLA-4 to block the binding of CD28 to CD80/CD86 may result in different outcomes during the clinical course of an autoimmune disease.

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Section: Sctla-4 and Autoimmune Diseasescontrasting

confidence: 56%

Section: Soluble Form Of Ctla-4mentioning

confidence: 99%

Section: Soluble Form Of Ctla-4mentioning

confidence: 99%

Section: Sctla-4 and Autoimmune Diseasesmentioning

confidence: 99%

See 2 more Smart Citations

The soluble CTLA-4 receptor and its role in autoimmune diseases: an update

Saverino

Simone

Bagnasco

et al. 2010

Autoimmun Highlights

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“…It is therefore not surprising that the abnormal function of the molecule has been implicated in the aetiology of several autoimmune diseases including vitiligo [46][47][48]. Indeed, both soluble (sCTLA-4) and full-length (flCTLA-4) CTLA-4 mRNA have been found at decreased levels in vitiligo patients, which could perturb the normal suppressive capacity of Tregs [46].…”

Section: Cytotoxic T Lymphocyte Antigen-4mentioning

confidence: 99%

Regulatory T cells in vitiligo: Implications for pathogenesis and therapeutics

Dwivedi

Kemp

Laddha

et al. 2015

Autoimmunity Reviews

111

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Vitiligo is a hypomelanotic autoimmune skin disease arising from a breakdown in immunological self-tolerance, which leads to aberrant immune responses against melanocytes.Regulatory T cells (Tregs) are crucial to the development of self-tolerance and so are major foci in the study of autoimmune pathogenesis of vitiligo. This review will summarise recent findings concerning the role of Tregs in the pathogenesis of vitiligo. In addition, as antigen-specific Tregs are a potential route for the reinstatement of immune tolerance, new strategies that expand or induce de novo generation of Tregs and which are currently being investigated as therapies for other autoimmune diseases, will be discussed. These approaches will highlight the opportunities for Treg cell-based therapeutics in vitiligo.4

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