Glikozilacija imunoglobulina G u osoba s Downovim sindromom

master's thesis

• Title (english): Immunoglobulin G glycosylation in people with Down syndrome
• Author: Ana Cindrić
• Mentor: Gordan Lauc (mentor)
• Mentor: Damjan Franjević (mentor)
• Committee member: Damjan Franjević (predsjednik povjerenstva)
• Committee member: Sven Jelaska (član povjerenstva)
• Committee member: Biljana Balen (član povjerenstva)
• Committee member: Inga Marijanović (član povjerenstva)
• Granter: University of Zagreb; Faculty of Science; (Department of Biology); Zagreb
• Defense date and country: 2019-02-19, Croatia
• Scientific / art field, discipline and subdiscipline: NATURAL SCIENCES; Biology

Abstract

Glikozilacija je posttranslacijska modifikacija koja utječe na strukturu i funkciju proteina. Promjene u glikozilaciji imunoglobulina G (IgG), važne efektorske molekule imunološkog sustava, usko koreliraju s kronološkom dobi, a uočene su i kod brojnih bolesti. Jedan od simptoma Downovog sindroma je preuranjeno starenje, koje se posebno očituje u promjenama središnjeg živčanog sustava i imunološkog sustava. Cilj istraživanja bio je utvrditi imaju li osobe s Downovim sindromom različit profil glikozilacije IgG-a u odnosu na njihove zdrave vršnjake te, ukoliko imaju, u smislu IgG-a kao biomarkera starenja, ustanoviti očitava li se preuranjeno starenje karakteristično za osobe s Downovim sindromom u njihovom glikolizacijskom profilu IgG-a. Također, zbog prisutnosti treće kopije gena B3GALT5 u osoba s Downovom sindromom, istraženo je imaju li glikani IgG-a osoba s Downovim sindromom u svom sastavu galaktozu vezanu β-1,3 vezom. Analizom tekućinskom kromatografijom ultravisoke djelotvornosti otkriveno je da u osoba s Downovim sindromom postoje značajne razlike u udjelu pojedinih glikana IgG-a u odnosu na zdrave kontrole, te je ustanovljeno da te razlike odražavaju postojanje preuranjenog starenja u osoba s Downovim sindromom. Nadalje, pomoću digestija glikozidazama u osoba s Downovim sindromom unatoč prisutnosti treće kopije gena B3GALT5 nisu opažene mjerljive količine glikana IgG-a u čijem je sastavu galaktoza vezana β-1,3 vezom.

Abstract (english)

Glycosylation is a posttranslational modification that impacts the structure and function of proteins. Changes in immunoglobulin G (IgG) glycosylation correlate to age and the onset of many diseases. An important symptom of Down syndrome (DS) are premature signs of aging, which have notable consequences for the central nervous system and the immune system. The goal of this research was to determine whether people with DS show a different IgG glycan composition to their healthy peers and, if so, using IgG glycans as biomarkers of age, to see if these changes are connected to the symptom of premature aging. Also, due to the presence of a third copy of the B3GALT5 gene in DS, the existence of β-1,3 linked galactose in DS IgG glycans was researched. Ultra performance liquid chromatography analysis of IgG glycans of people with DS and their healthy peers clarified that there are significant differences in the composition of their IgG glycans, and also that these differences in composition correlate to premature aging. Furthermore, despite the presence of the third copy of the B3GALT5 gene, the use of glycosidase digestions did not detect measurable quantities of glycans containing β-1,3 linked galactose.

• Keywords: glikani; profil glikozilacije; preuranjeno starenje; B3GALT5
• Keywords (english): glycans; glycoprofile; premature aging; B3GALT5
• Language: croatian
• URN:NBN: urn:nbn:hr:217:978119
• Study programme: Title: Molecular Biology; Study programme type: university; Study level: graduate; Academic / professional title: magistar/magistra molekularne biologije (magistar/magistra molekularne biologije)
• Type of resource: Text
• File origin: Born digital
• Access conditions: Open access; Embargo expiration date: 2021-02-19
• Created on: 2019-04-02 08:23:28