titoli, abstracts, parole chiave >>>
Immunogenecity of Mycobacterium avium subsp. paratuberculosis epitopes cross-reacting with human ZnT8 and proinsulin peptides in autoimmune diabetes

Niegowska Conforti, Magdalena (2018) Immunogenecity of Mycobacterium avium subsp. paratuberculosis epitopes cross-reacting with human ZnT8 and proinsulin peptides in autoimmune diabetes. Doctoral Thesis.

[img]
Preview
Full text disponibile come PDF Richiede visualizzatore di PDF come GSview, Xpdf o Adobe Acrobat Reader
5Mb

Abstract

Although numerous studies put in evidence the increasing incidence of type 1 diabetes (T1D), its cause remains unclear. The role of Mycobacterium avium subsp. paratuberculosis (MAP) as a putative environmental agent triggering or accelerating the disease has been previously hypothesized in Sardinian and Italian T1D populations. The present thesis further sustains this association by reporting an elevated seroreactivity to MAP-derived epitopes and homologous human peptides corresponding to proinsulin and ZnT8 fragments in populations at different T1D stages and originating from distinct biogeographic backgrounds. Anti-MAP antibodies (Abs) resulted detectable in the first months of life before the appearance of classical autoantigens and, in most cases, were maintained in time making the selected peptides good candidates for early biomarkers. Likewise, Abs responses to the same antigens were observed among LADA patients and subjects affected by Hashimoto’s thyroiditis which frequently complicates T1D. Validation with a MAP-specific lipopentapeptide confirmed these results in coincidence with a stable Abs status. In PBMC primary culture, ZnT8 peptide and its MAP homolog induced the expression of proinflammatory cytokines along with increased cell-mediated responses and apoptosis. Good correlation between values obtained for the homologous MAP/human peptide pairs point at cross-reactivity through which mechanisms of self tolerance may be disrupted leading to autoimmunity.

Item Type:Doctoral Thesis
ID Code:11870
Contributors:Sechi, Leonardo Antonio
Publisher:Universita' degli studi di Sassari
Uncontrolled Keywords:Mycobacterium avium subsp. paratuberculosis, diabete, tiroidite Hashimoto, ZnT8, proinsulina
Subjects:Area 06 - Scienze mediche > MED/07 Microbiologia e microbiologia clinica
Divisions:001 Università di Sassari > 01-a Nuovi Dipartimenti dal 2012 > Scienze Biomediche
Cicli, scuole e corsi:Ciclo 30 > Life sciences and biotechnologies > Microbiologia e immunologia
Deposited On:07 Jun 2018 15:34

I documenti depositati in UnissResearch sono protetti dalle leggi che regolano il diritto d'autore

Repository Staff Only: item control page