Serum titres of anti-glutamic acid decarboxylase-65 and anti-IA-2 autoantibodies are associated with different immunoregulatory milieu in newly diagnosed type 1 diabetes patients

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dc.contributor.authorAndrade Lima Gabbay, M.
dc.contributor.authorSato, M. N. [UNESP]
dc.contributor.authorDuarte, A. J. S. [UNESP]
dc.contributor.authorDib, S. A.
dc.contributor.institutionUniversidade Federal de São Paulo (UNIFESP)
dc.contributor.institutionUniversidade Estadual Paulista (Unesp)
dc.date.accessioned2014-05-20T15:33:41Z
dc.date.available2014-05-20T15:33:41Z
dc.date.issued2012-04-01
dc.description.abstractSeveral studies correlated genetic background and pancreatic islet-cell autoantibody status (type and number) in type 1A diabetes mellitus (T1AD), but there are no data evaluating the relationship among these markers with serum cytokines, regulatory T cells and beta cell function. This characterization has a potential importance with regard to T1AD patients' stratification and follow-up in therapeutic prevention. In this study we showed that peripheral sera cytokines [interleukin (IL)-12, IL-6, II-1 beta, tumour necrosis factor (TNF)-a, IL-10] and chemokines (CXCL10, CXCL8, CXCL9, CCL2) measured were significantly higher in newly diagnosed T1AD patients when compared to healthy controls (P < 0.001). Among T1AD, we found a positive correlation between CXCL10 and CCL-2 (r = 0.80; P = 0.000), IL-8 and TNF-alpha (r = 0.60; P = 0.000); IL-8 and IL-12 (r = 0.57; P = 0.001) and TNF-alpha and IL-12 (r = 0.93; P = 0.000). Glutamic acid decarboxylase-65 (GAD-65) autoantibodies (GADA) were associated negatively with CXCL10 (r = -0.45; P = 0.011) and CCL2 (r = -0.65; P = 0.000), while IA-2A showed a negative correlation with IL-10 (r = -0.38; P = 0.027). Human leucocyte antigen (HLA) DR3, DR4 or DR3/DR4 and PTPN22 polymorphism did not show any association with pancreatic islet cell antibodies or cytokines studied. In summary, our results revealed that T1AD have a proinflammatory cytokine profile compared to healthy controls and that IA-2A sera titres seem to be associated with a more inflammatory peripheral cytokine/chemokine profile than GADA. A confirmation of these data in the pre-T1AD phase could help to explain the mechanistic of the well-known role of IA-2A as a more specific marker of beta-cell damage than GADA during the natural history of T1AD.en
dc.description.affiliationUniv Fed São Paulo, Ctr Diabet, Div Endocrinol, Dept Med, BR-04039032 São Paulo, Brazil
dc.description.affiliationSão Paulo State Univ, Immunol Lab, São Paulo, Brazil
dc.description.affiliationUnespSão Paulo State Univ, Immunol Lab, São Paulo, Brazil
dc.description.sponsorshipFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
dc.description.sponsorshipCoordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)
dc.format.extent60-67
dc.identifierhttp://dx.doi.org/10.1111/j.1365-2249.2011.04538.x
dc.identifier.citationClinical and Experimental Immunology. Malden: Wiley-blackwell, v. 168, n. 1, p. 60-67, 2012.
dc.identifier.doi10.1111/j.1365-2249.2011.04538.x
dc.identifier.issn0009-9104
dc.identifier.urihttp://hdl.handle.net/11449/42249
dc.identifier.wosWOS:000300974800010
dc.language.isoeng
dc.publisherWiley-Blackwell
dc.relation.ispartofClinical and Experimental Immunology
dc.relation.ispartofjcr3.542
dc.relation.ispartofsjr1,431
dc.rights.accessRightsAcesso restrito
dc.sourceWeb of Science
dc.subjectcytokineen
dc.subjectpancreatic autoantibodiesen
dc.subjectregulatory T cellsen
dc.subjecttype 1 diabetesen
dc.titleSerum titres of anti-glutamic acid decarboxylase-65 and anti-IA-2 autoantibodies are associated with different immunoregulatory milieu in newly diagnosed type 1 diabetes patientsen
dc.typeArtigo
dcterms.licensehttp://olabout.wiley.com/WileyCDA/Section/id-406071.html
dcterms.rightsHolderWiley-blackwell

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