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A functional soluble form of CTLA-4 is present in the serum of celiac patients and correlates with mucosal injury.
Simone, Rita; Brizzolara, Renata; Chiappori, Alessandra; Milintenda-Floriani, Francesca; Natale, Clelia; Greco, Luigi; Schiavo, Mara; Bagnasco, Marcello; Pesce, Giampaola; Saverino, Daniele.
Afiliação
  • Simone R; Section of Human Anatomy, Department of Experimental Medicine, University of Genova, Genova, Italy.
Int Immunol ; 21(9): 1037-45, 2009 Sep.
Article em En | MEDLINE | ID: mdl-19625381
Celiac disease (CD) is a multifactorial disorder influenced by environmental, genetic and immunological factors. Increasing evidence showed CTLA-4 gene as an important susceptibility locus for autoimmune disorders. A native soluble cytotoxic T-lymphocyte-associated protein-4 (sCTLA-4), lacking of transmembrane sequence, has been described in several autoimmune diseases. We aimed to evaluate the presence of increased sCTLA-4 concentration in the serum of patients with CD and the possible immunoregulatory function. Blood samples were collected from 160 CD patients; sCTLA-4 levels were evaluated by ELISA, western blot and reverse transcription-PCR. The capability of serum sCTLA-4 to modulate T-lymphocyte proliferation in vitro was evaluated by two-way mixed leukocyte reaction assay. We demonstrated high levels of sCTLA-4 in serum of untreated celiac patients. Additionally, we observed that sCTLA-4 concentrations are related to gluten intake and that a correlation between autoantibodies to tissue transglutaminase and sCTLA-4 concentration exists. Moreover, sCTLA-4 levels correlate with the degree of mucosal damage. Conversely, no correlation between sCTLA4 levels and the HLA-related risk was observed. Finally, we show that sCTLA-4 from sera of CD patients displays functional activities. These results strongly suggest a regulation of sCTLA-4 synthesis depending on the presence or absence of dietary gluten and imply a possible immunomodulatory effect on cytotoxic T lymphocyte functions. In gluten-exposed patients, serum sCTLA-4 levels might provide insight about mucosal injury.
Assuntos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Antígenos CD / Doença Celíaca / Mucosa Intestinal Limite: Adolescent / Adult / Aged / Child / Child, preschool / Humans / Infant / Middle aged Idioma: En Revista: Int Immunol Assunto da revista: ALERGIA E IMUNOLOGIA Ano de publicação: 2009 Tipo de documento: Article País de afiliação: Itália

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Antígenos CD / Doença Celíaca / Mucosa Intestinal Limite: Adolescent / Adult / Aged / Child / Child, preschool / Humans / Infant / Middle aged Idioma: En Revista: Int Immunol Assunto da revista: ALERGIA E IMUNOLOGIA Ano de publicação: 2009 Tipo de documento: Article País de afiliação: Itália