1. N-glycosylation of immunoglobulin G in infalmmatory bowel disease
- Author
-
Šimurina, Mirna and Lauc, Gordan
- Subjects
glikopeptidi ,Pharmacology. Therapeutics. Toxicology ,glycopeptides ,nanoLC-MS ,BIOMEDICINE AND HEALTHCARE. Pharmacy. Medical Biochemistry ,udc:615(043.3) ,fukozilacija ,Chronova bolest ,immunoglobulin G ,Crohn's disease ,ulcerozni kolitis ,Fcglycosylation ,Fcglikozilacija ,inflammatory bowel disease ,Farmakologija. Terapeutika. Toksikologija ,fucosylation ,BIOMEDICINA I ZDRAVSTVO. Farmacija. Medicinska biokemija ,galactosylation ,upalna bolest crijeva ,galaktozilacija ,ulcerative colitis - Abstract
Uzrok upalne bolesti crijeva (eng. inflammatory bowel disease, IBD) nije još uvijek potpuno razjašnjen te je ponekad teško razlikovati najučestalije oblike, Crohnovu bolest (eng. Crohn’s disease, CD) i ulcerozni kolitis (eng. ulcerative colitis, UC). Glikozilacija imunoglobulina G (IgG) povezuje se s CD-om i UC-om. Fc-glikozilacija IgG-a (fragment koji kristalizira, eng. fragment crystallizable, Fc) utječe na njegove efektorske funkcije. Analizirane su promjene u Fc-glikozilaciji IgG-a povezane s UC-om i CD-om kao i s kliničkim obilježjima ovih bolesti u različitim skupinama ispitanika te je ovo prva studija upalne bolesti crijeva u kojoj je analizirana glikozilacija IgG-a po potklasama. U retrospektivnoj studiji prikupljeno je ukupno 2 357 uzoraka krvne plazme pacijenata oboljelih od UC-a (1056) i CD-a (874) te zdravih ispitanika (eng. healthy controls, HC, 427). Ovo je dosad najveće provedeno istraživanje glikozilacije IgG-a u IBD-u. Tekućinskom kromatografijom spregnutom sa spektrometrijom masa (eng. nano-liquid chromatography-mass spectrometry, nanoLC-MS) analizirana je Fc-glikozilacija IgG-a po potklasama (glikopeptidi dobiveni djelovanjem tripsina). Ispitivana je povezanost između pojedinih skupina (UC vs HC, CD vs HC i UC vs CD) i glikopeptida te povezanost između kliničkih obilježja bolesti i glikopeptida. Kod pacijenata oboljelih od CD-a i UC-a, zabilježena je niža razina galaktozilacije IgG-a u odnosu na kontrole. Fukozilacija IgG-a je bila povećana kod oboljelih od CD-a naspram HC-a, ali snižena kod oboljelih od UC-a naspram HC-a. Snižena galaktozilacija se povezuje s težim oblicima CD-a i UC-a, uključujući i potrebu za operacijom. U retrospektivnoj analizi uzoraka krvne plazme pacijenata oboljelih od CD-a i UC-a, IgG Fc-glikozilacija je povezana s navedenim bolestima (u usporedbi s kontrolama) i njihovim kliničkim obilježjima. Rezultati ovoga istraživanja bi mogli, kroz bolju klasifikaciju pacijenata, pridonijeti The cause of inflammatory bowel disease (IBD) is still poorly understood and the most prominent forms Crohn’s disease (CD) and ulcerative colitis (UC) are sometimes hard to distinguish. Glycosylation of immunoglobulin G (IgG) has been associated with CD and UC. IgG Fc-glycosylation affects IgG effector functions. The changes in IgG Fc-glycosylation associated with UC and CD, as well as with disease characteristics in different patient groups, were evaluated, and this is the first study of inflammatory bowel disease where subclass-specific IgG gycosylation was analyzed. A total of 2 357 plasma samples were collected in retrospective cohort that contained samples from UC (1056) and CD patients (874) as well as healthy controls (HC, 427). So far, this is the largest study of IgG glycosylation in IBD. Subclass-specific IgG Fc-glycosylation (tryptic glycopeptides) was analyzed by liquid chromatography coupled to mass spectrometry (nanoLC-MS). Associations between disease status (UC vs HC, CD vs HC, and UC vs CD) and glycopetide traits and associations between clinical characteristics and glycopeptide traits, was performed. Patients with CD or UC had lower levels of IgG galactosylation than controls. Fucosylation of IgG was increased in patients with CD vs controls but decreased in patients with UC vs controls. Decreased galactosylation associated with more severe CD or UC, including the need for surgery. In a retrospective analysis of plasma samples from patients with CD or UC, we associated levels of IgG Fc-glycosylation with disease (compared to controls) and its clinical features. Through better patient classification, these findings could increase our understanding of mechanisms of CD and UC pathogenesis and be used to develop diagnostics or guide treatment.
- Published
- 2018