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Pregled bibliografske jedinice broj: 818480

Epigenetic deregulation of genes responsible for IgG glycosylation might be an important mechanism involved in pathogenesis of inflammatory bowel disease


Klasić, Marija; Markulin, Dora; Krištić, Jasminka; Biruš, Ivan; Vojta, Aleksandar; Lauc, Gordan; Zoldoš, Vlatka
Epigenetic deregulation of genes responsible for IgG glycosylation might be an important mechanism involved in pathogenesis of inflammatory bowel disease // 6th Clinical Epigenetics International Meeting
Dusseldorf, 2016. str. 14-14 (poster, međunarodna recenzija, sažetak, znanstveni)


CROSBI ID: 818480 Za ispravke kontaktirajte CROSBI podršku putem web obrasca

Naslov
Epigenetic deregulation of genes responsible for IgG glycosylation might be an important mechanism involved in pathogenesis of inflammatory bowel disease

Autori
Klasić, Marija ; Markulin, Dora ; Krištić, Jasminka ; Biruš, Ivan ; Vojta, Aleksandar ; Lauc, Gordan ; Zoldoš, Vlatka

Vrsta, podvrsta i kategorija rada
Sažeci sa skupova, sažetak, znanstveni

Izvornik
6th Clinical Epigenetics International Meeting / - Dusseldorf, 2016, 14-14

Skup
6th Clinical Epigenetics International Meeting

Mjesto i datum
Dusseldorf, Njemačka, 3.-4.3.2016

Vrsta sudjelovanja
Poster

Vrsta recenzije
Međunarodna recenzija

Ključne riječi
IBD ; N-glycosylation ; immunoglobulin G ; DNA methylation

Sažetak
Inflammatory bowel disease (IBD) is an immune-related disorder of gastrointestinal tract that includes ulcerative colitis and Crohn's disease. The mechanisms leading to IBD are complex and not yet well understood. The new evidence suggests that IBD results from an inappropriate inflammatory response and aberrant immune response to gut microbiota in genetically susceptible individuals. A meta-analysis of genome-wide association studies (GWAS) identified 163 IBD susceptibility loci, many of them being involved in pathways of protein glycosylation. Glycosylation is a post-translational modification of proteins where carbohydrate structures (glycans) are added by specific enzymes – glycosyltransferases. Some of the IBD GWAS loci show pleiotropy with the glycosylation of immunoglobulin G (IgG), one of the main components of the immune system. Alternative glycosylation of IgG defines its function converting IgG from anti- to pro-inflammatory antibody. We analysed promoter methylation of the five loci previously associated with both IBD and IgG glycosylation and showed that two of them, the BACH2 and MGAT3 genes, were differentially methylated in blood of IBD patients compared with healthy controls (HC). The MGAT3 is a glycosyltransferase involved in formation of bisecting GlcNAc structure on bianntenary glycans (of the Fc region of IgG), while the BACH2 is a transcription factor involved in maturation of B cells and their differentiation into plasma cells that excrete IgG. We also analysed IgG glycosylation in plasma of the same patients and revealed change in IgG galactosylation, sialylation and fucosylation – all modifications related to anti- inflammatory character of IgG. These results are concordant with decreased immunosuppressive and anti- inflammatory potential of IBD patients. The promoter methylation status of the MGAT3 and BACH2 in whole blood was positively correlated with IgG glycosylation in plasma of the same IBD patients. Our results strongly suggest that aberrant IgG glycosylation as a result of changed promoter methylation of relevant genes could be one of the important mechanisms involved in pathogenesis of IBD.

Izvorni jezik
Engleski

Znanstvena područja
Biologija



POVEZANOST RADA


Projekt / tema
315997
FP7-305479

Ustanove
Prirodoslovno-matematički fakultet, Zagreb

Citiraj ovu publikaciju

Klasić, Marija; Markulin, Dora; Krištić, Jasminka; Biruš, Ivan; Vojta, Aleksandar; Lauc, Gordan; Zoldoš, Vlatka
Epigenetic deregulation of genes responsible for IgG glycosylation might be an important mechanism involved in pathogenesis of inflammatory bowel disease // 6th Clinical Epigenetics International Meeting
Dusseldorf, 2016. str. 14-14 (poster, međunarodna recenzija, sažetak, znanstveni)
Klasić, M., Markulin, D., Krištić, J., Biruš, I., Vojta, A., Lauc, G. & Zoldoš, V. (2016) Epigenetic deregulation of genes responsible for IgG glycosylation might be an important mechanism involved in pathogenesis of inflammatory bowel disease. U: 6th Clinical Epigenetics International Meeting.
@article{article, year = {2016}, pages = {14-14}, keywords = {IBD, N-glycosylation, immunoglobulin G, DNA methylation}, title = {Epigenetic deregulation of genes responsible for IgG glycosylation might be an important mechanism involved in pathogenesis of inflammatory bowel disease}, keyword = {IBD, N-glycosylation, immunoglobulin G, DNA methylation}, publisherplace = {Dusseldorf, Njema\v{c}ka} }