Analiza glikolizacije imunoglobulina G u upalnoj bolesti crijeva tekućinskom kromatografijom

doctoral thesis

• Title (english): Glycosylation analysis of immunoglobulin G in inflammatory bowel disease by liquid chromatography
• Author: Irena Trbojević Akmačić; MBZ: 351184
• Mentor: Gordan Lauc (mentor)
• Committee member: Boris Mildner (predsjednik povjerenstva)
• Committee member: Olga Gornik (član povjerenstva)
• Committee member: Vlasta Drevenkar (član povjerenstva)
• Granter: University of Zagreb; Faculty of Science; (Department of Chemistry); Zagreb
• Defense date and country: 2015-11-27, Croatia
• Scientific / art field, discipline and subdiscipline: NATURAL SCIENCES; Chemistry
• Universal decimal classification (UDC): 54 - Chemistry. Crystallography. Mineralogy

Abstract

Sažetak Upalna bolest crijeva je kroniĉni upalni poremećaj gastrointestinalnog trakta za koji se smatra da je rezultat meĊudjelovanja genskih i okolišnih ĉimbenika. Genetiĉka israţivanja su pokazala da postoji povezanost gena koji sudjeluju u regulaciji glikozilacije IgG-a i upalne bolesti crijeva. N-glikozilacija IgG-a utjeĉe na njegovu strukturu i imunološku funkciju. U ovoj disertaciji analizirana je N-glikozilacija IgG-a kod 804 pacijenta s upalnom bolesti crijeva i zdravih ispitanika, što je dosad najveće istraţivanje glikana u upalnoj bolesti crijeva. Pokazano je da su galaktozilirane glikoforme IgG-a statistiĉki znaĉajno manje zastupljene kod pacijenata koji boluju od Crohnove bolesti i ulceroznog kolitisa u odnosu na zdrave ispitanike. Monosijalinizirane glikoforme su statistiĉki znaĉajno manje zastupljene kod pacijenata koji boluju od Crohnove bolesti. Uoĉena je veća zastupljenost glikoformi s raĉvajućim GlcNAc-om u upalnoj bolesti crijeva u odnosu na zdrave ispitanike. IgG ima potencijal kao dijagnostiĉki i prognostiĉki biomarker za upalnu bolest crijeva. Tijekom studije evaluirana je metoda HILIC-UPLC, te je razvijena, optimirana i validirana nova visoko-protoĉna metoda priprave N-glikana za analizu tekućinskom kromatografijom. Poboljšanje metodologije će omogućiti toĉniju i informativniju analizu N-vezanih glikana u budućnosti.

Abstract (english)

Inflammatory bowel disease is chronic inflammatory disorder of the gastrointestinal tract which is considered to be the result of the interaction of genetic and environmental factors. Genetic studies have shown pleiotropy between IgG glycosylation and inflammatory bowel disease. IgG N-glycosylation affects its structure and immune function. IgG N-glycosylation in 804 inflammatory bowel disease patients and healthy controls was analyzed within this dissertation, which makes it the largest study of glycans in inflammatory bowel disease. The results demonstrated statistically significant decrease in IgG galactosylation in Crohn's disease and ulcerative colitis compared to healthy controls, as well as statistically significant decrease in IgG monosialylation in Crohns disease. Increase in proportion of structures with bisecting GlcNAc was observed in inflammatory bowel disease patients compared to healthy controls. Therefore, IgG has a potential as diagnostic and prognostic biomarker for inflammatory bowel disease. Within this dissertation HILIC-UPLC method was validated, and new high-throughput preparation method for N-glycan analysis by liquid chromatography was developed, optimized, and validated. Improved methodology will enable more accurate and informative N-glycan analysis in the future.

• Keywords: Crohnova bolest; HILIC; imunoglobulin G; N-glikozilacija; tekućinska kromatografija; ulcerozni kolitis; upalna bolest crijeva
• Keywords (english): Crohn's disease; HILIC; immunoglobulin G; inflammatory bowel disease; liquid chromatography; N-glycosylation; ulcerative colitis
• Language: croatian
• URN:NBN: urn:nbn:hr:217:966604
• Study programme: Title: Doctoral study in chemistry; Study programme type: university; Study level: postgraduate; Academic / professional title: doktor/doktorica znanosti, područje prirodnih znanosti, polje kemija (doktor/doktorica znanosti, područje prirodnih znanosti, polje kemija)
• Type of resource: Text
• Extent: 175 str. ; 30 cm
• File origin: Born digital
• Access conditions: Open access
• Created on: 2017-02-13 11:37:04