title: Association of systemic lupus erythematosus with decreased immunosuppressive potential of the IgG glycome.
abstract: OBJECTIVE
  Glycans attached to the Fc portion of IgG are important modulators of IgG effector functions. Interindividual differences in IgG glycome composition are large and they associate strongly with different inflammatory and autoimmune diseases. IKZF1, HLA-DQ2A/B, and BACH2 genetic loci that affect IgG glycome composition show pleiotropy with systemic lupus erythematosus (SLE), indicating a potentially causative role of aberrant IgG glycosylation in SLE. We undertook this large multicenter case-control study to determine whether SLE is associated with altered IgG glycosylation.
  
  
  METHODS
  Using ultra-performance liquid chromatography analysis of released glycans, we analyzed the composition of the IgG glycome in 261 SLE patients and 247 matched controls of Latin American Mestizo origin (the discovery cohort) and in 2 independent replication cohorts of different ethnicity (108 SLE patients and 193 controls from Trinidad, and 106 SLE patients and 105 controls from China).
  
  
  RESULTS
  Multiple statistically significant differences in IgG glycome composition were observed between patients and controls. The most significant changes included decreased galactosylation and sialylation of IgG (which regulate proinflammatory and antiinflammatory actions of IgG) as well as decreased core fucose and increased bisecting N-acetylglucosamine (which affect antibody-dependent cell-mediated cytotoxicity).
  
  
  CONCLUSIONS
  The IgG glycome in SLE patients is significantly altered in a way that decreases immunosuppressive action of circulating immunoglobulins. The magnitude of observed changes is associated with the intensity of the disease, indicating that aberrant IgG glycome composition or changes in IgG glycosylation may be an important molecular mechanism in SLE.
authors.affiliation: Genos Ltd., Glycoscience Research Laboratory, Zagreb, Croatia.
authors.forename: Frano
authors.initials: F
authors.lastname: Vučković
authors.affiliation: Genos Ltd., Glycoscience Research Laboratory, Zagreb, Croatia.
authors.forename: Jasminka
authors.initials: J
authors.lastname: Krištić
authors.affiliation: Genos Ltd., Glycoscience Research Laboratory, Zagreb, Croatia.
authors.forename: Ivan
authors.initials: I
authors.lastname: Gudelj
authors.affiliation: Pfizer-University of Granada-Junta de Andalucia Centre for Genomics and Oncological Research (GENYO), Granada, Spain.
authors.forename: Maria
authors.initials: M
authors.lastname: Teruel
authors.affiliation: University of Zagreb, Zagreb, Croatia.
authors.forename: Toma
authors.initials: T
authors.lastname: Keser
authors.affiliation: Genos Ltd., Glycoscience Research Laboratory, Zagreb, Croatia.
authors.forename: Marija
authors.initials: M
authors.lastname: Pezer
authors.affiliation: Genos Ltd., Glycoscience Research Laboratory, Zagreb, Croatia.
authors.forename: Maja
authors.initials: M
authors.lastname: Pučić-Baković
authors.affiliation: Genos Ltd., Glycoscience Research Laboratory, Zagreb, Croatia.
authors.forename: Jerko
authors.initials: J
authors.lastname: Štambuk
authors.affiliation: Genos Ltd., Glycoscience Research Laboratory, Zagreb, Croatia.
authors.forename: Irena
authors.initials: I
authors.lastname: Trbojević-Akmačić
authors.affiliation: King's College London, London, UK, and Hospital del Mar and Institut Mar d'Investigacions Mediques, Barcelona, Spain.
authors.forename: Clara
authors.initials: C
authors.lastname: Barrios
authors.affiliation: University of Zagreb, Zagreb, Croatia.
authors.forename: Tamara
authors.initials: T
authors.lastname: Pavić
authors.affiliation: King's College London, London, UK.
authors.forename: Cristina
authors.initials: C
authors.lastname: Menni
authors.affiliation: Capital Medical University, Beijing, China.
authors.forename: Youxin
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Beijing Tiantan Hospital and Capital Medical University, Beijing, China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Zhou
authors.affiliation: Affiliated Kailuan General Hospital of Hebei United University, Tangshan, China.
authors.forename: Liufu
authors.initials: L
authors.lastname: Cui
authors.affiliation: Affiliated Kailuan General Hospital of Hebei United University, Tangshan, China.
authors.forename: Haicheng
authors.initials: H
authors.lastname: Song
authors.affiliation: International Medical Center and Chinese People's Liberation Army General Hospital, Beijing, China.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Zeng
authors.affiliation: Capital Medical University, Beijing, China.
authors.forename: Xiuhua
authors.initials: X
authors.lastname: Guo
authors.affiliation: Sanatorio Parque, Rosario, Argentina.
authors.forename: Bernardo A
authors.initials: BA
authors.lastname: Pons-Estel
authors.affiliation: University of Edinburgh, Edinburgh, UK.
authors.forename: Paul
authors.initials: P
authors.lastname: McKeigue
authors.affiliation: Kavanagh Street Medical Centre, Port of Spain, Trinidad, West Indies.
authors.forename: Alan
authors.initials: A
authors.lastname: Leslie Patrick
authors.affiliation: University of Zagreb, Zagreb, Croatia.
authors.forename: Olga
authors.initials: O
authors.lastname: Gornik
authors.affiliation: King's College London, London, UK.
authors.forename: Tim D
authors.initials: TD
authors.lastname: Spector
authors.affiliation: Clinical Hospital Center Sestre Milosrdnice, Zagreb, Croatia.
authors.forename: Miroslav
authors.initials: M
authors.lastname: Harjaček
authors.affiliation: Pfizer-University of Granada-Junta de Andalucia Centre for Genomics and Oncological Research (GENYO), Granada, Spain, and Oklahoma Medical Research Foundation, Oklahoma City.
authors.forename: Marta
authors.initials: M
authors.lastname: Alarcon-Riquelme
authors.affiliation: King's College London, London, UK.
authors.forename: Mariam
authors.initials: M
authors.lastname: Molokhia
authors.affiliation: Capital Medical University, Beijing, China, and Edith Cowan University, Perth, Western Australia, Australia.
authors.forename: Wei
authors.initials: W
authors.lastname: Wang
authors.affiliation: Genos Ltd., Glycoscience Research Laboratory, and University of Zagreb, Zagreb, Croatia.
authors.forename: Gordan
authors.initials: G
authors.lastname: Lauc
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D016022:Case-Control Studies; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D007074:Immunoglobulin G / Q000235:genetics* / Q000276:immunology / Q000378:metabolism; D008180:Lupus Erythematosus, Systemic / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D055815:Young Adult; D006023:Glycoproteins
chemical_list: D007074:Immunoglobulin G; C046179:glycosylated IgG; D006023:Glycoproteins