TY - JOUR
T1 - Glycosylation of Immunoglobulin G Associates With Clinical Features of Inflammatory Bowel Diseases
AU - Šimurina, Mirna
AU - de Haan, Noortje
AU - Vučković, Frano
AU - Kennedy, Nicholas A.
AU - Štambuk, Jerko
AU - Falck, David
AU - Trbojević-Akmačić, Irena
AU - Clerc, Florent
AU - Razdorov, Genadij
AU - Khon, Anna
AU - Latiano, Anna
AU - D'Incà, Renata
AU - Danese, Silvio
AU - Targan, Stephan
AU - Landers, Carol
AU - Dubinsky, Marla
AU - Campbell, Harry
AU - Zoldoš, Vlatka
AU - Permberton, Iain K.
AU - Kolarich, Daniel
AU - Fernandes, Daryl L.
AU - Theorodorou, Evropi
AU - Merrick, Victoria
AU - Spencer, Daniel I.
AU - Gardner, Richard A.
AU - Doran, Ray
AU - Shubhakar, Archana
AU - Boyapati, Ray
AU - Rudan, Igor
AU - Lionetti, Paolo
AU - Krištić, Jasminka
AU - Novokmet, Mislav
AU - Pučić-Baković, Maja
AU - Gornik, Olga
AU - Andriulli, Angelo
AU - Cantoro, Laura
AU - Sturniolo, Giancarlo
AU - Fiorino, Gionata
AU - Manetti, Natalia
AU - Arnott, Ian D.
AU - Noble, Colin L.
AU - Lees, Charlie W.
AU - Shand, Alan G.
AU - Ho, Gwo Tzer
AU - Dunlop, Malcolm G.
AU - Murphy, Lee
AU - Gibson, Jude
AU - Evenden, Louise
AU - Wrobel, Nicola
AU - Gilchrist, Tamara
AU - Fawkes, Angie
AU - Kammeijer, Guinevere S.M.
AU - Vojta, Aleksandar
AU - Samaržija, Ivana
AU - Markulin, Dora
AU - Klasić, Marija
AU - Dobrinić, Paula
AU - Aulchenko, Yurii
AU - van den Heuve, Tim
AU - Jonkers, Daisy
AU - Pierik, Marieke
AU - McGovern, Dermot P.B.
AU - Annese, Vito
AU - Wuhrer, Manfred
AU - Lauc, Gordan
AU - The Inflammatory Bowel Disease Biomarkers Consortium
PY - 2018/4/1
Y1 - 2018/4/1
N2 - Background and Aims: Causes of inflammatory bowel diseases are not well understood and the most prominent forms, Crohn's disease (CD) and ulcerative colitis (UC), are sometimes hard to distinguish. Glycosylation of IgG has been associated with CD and UC. IgG Fc-glycosylation affects IgG effector functions. We evaluated changes in IgG Fc-glycosylation associated with UC and CD, as well as with disease characteristics in different patient groups. Methods: We analyzed 3441 plasma samples obtained from 2 independent cohorts of patients with CD (874 patients from Italy and 391 from the United States) or UC (1056 from Italy and 253 from the US and healthy individuals [controls]; 427 in Italy and 440 from the United States). IgG Fc-glycosylation (tryptic glycopeptides) was analyzed by liquid chromatography coupled to mass spectrometry. We analyzed associations between disease status (UC vs controls, CD vs controls, and UC vs CD) and glycopeptide traits, and associations between clinical characteristics and glycopeptide traits, using a logistic regression model with age and sex included as covariates. Results: Patients with CD or UC had lower levels of IgG galactosylation than controls. For example, the odds ratio (OR) for IgG1 galactosylation in patients with CD was 0.59 (95% confidence interval [CI], 0.51–0.69) and for patients with UC was 0.81 (95% CI, 0.71–0.92). Fucosylation of IgG was increased in patients with CD vs controls (for IgG1: OR, 1.27; 95% CI, 1.12–1.44), but decreased in patients with UC vs controls (for IgG23: OR, 0.72; 95% CI, 0.63–0.82). Decreased galactosylation associated with more severe CD or UC, including the need for surgery in patients with UC vs controls (for IgG1: OR, 0.69; 95% CI, 0.54–0.89) and in patients with CD vs controls (for IgG23: OR, 0.78; 95% CI, 0.66–0.91). Conclusions: 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. These findings could increase our understanding of mechanisms of CD and UC pathogenesis and be used to develop diagnostics or guide treatment.
AB - Background and Aims: Causes of inflammatory bowel diseases are not well understood and the most prominent forms, Crohn's disease (CD) and ulcerative colitis (UC), are sometimes hard to distinguish. Glycosylation of IgG has been associated with CD and UC. IgG Fc-glycosylation affects IgG effector functions. We evaluated changes in IgG Fc-glycosylation associated with UC and CD, as well as with disease characteristics in different patient groups. Methods: We analyzed 3441 plasma samples obtained from 2 independent cohorts of patients with CD (874 patients from Italy and 391 from the United States) or UC (1056 from Italy and 253 from the US and healthy individuals [controls]; 427 in Italy and 440 from the United States). IgG Fc-glycosylation (tryptic glycopeptides) was analyzed by liquid chromatography coupled to mass spectrometry. We analyzed associations between disease status (UC vs controls, CD vs controls, and UC vs CD) and glycopeptide traits, and associations between clinical characteristics and glycopeptide traits, using a logistic regression model with age and sex included as covariates. Results: Patients with CD or UC had lower levels of IgG galactosylation than controls. For example, the odds ratio (OR) for IgG1 galactosylation in patients with CD was 0.59 (95% confidence interval [CI], 0.51–0.69) and for patients with UC was 0.81 (95% CI, 0.71–0.92). Fucosylation of IgG was increased in patients with CD vs controls (for IgG1: OR, 1.27; 95% CI, 1.12–1.44), but decreased in patients with UC vs controls (for IgG23: OR, 0.72; 95% CI, 0.63–0.82). Decreased galactosylation associated with more severe CD or UC, including the need for surgery in patients with UC vs controls (for IgG1: OR, 0.69; 95% CI, 0.54–0.89) and in patients with CD vs controls (for IgG23: OR, 0.78; 95% CI, 0.66–0.91). Conclusions: 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. These findings could increase our understanding of mechanisms of CD and UC pathogenesis and be used to develop diagnostics or guide treatment.
KW - Biomarker
KW - Glycans
KW - Glycopeptides
KW - IBD
UR - http://www.scopus.com/inward/record.url?scp=85044617800&partnerID=8YFLogxK
U2 - 10.1053/j.gastro.2018.01.002
DO - 10.1053/j.gastro.2018.01.002
M3 - Article
C2 - 29309774
AN - SCOPUS:85044617800
SN - 0016-5085
VL - 154
SP - 1320-1333.e10
JO - Gastroenterology
JF - Gastroenterology
IS - 5
ER -