High-throughput characterization of the functional impact of IgG Fc glycan aberrancy in juvenile idiopathic arthritis.
Glycobiology
; 27(12): 1099-1108, 2017 12 01.
Article
em En
| MEDLINE
| ID: mdl-28973482
ABSTRACT
Juvenile idiopathic arthritis (JIA) encompasses all forms of chronic idiopathic arthritis that arise before age 16. Previous studies have found JIA to be associated with lower Fc galactosylation of circulating IgG, but the overall spectrum of glycan changes and the net impact on IgG function are unknown. Using ultra performance liquid chromatography (UPLC), we compared IgG glycosylation in 54 subjects with recent-onset untreated JIA with 98 healthy pediatric controls, paired to biophysical profiling of affinity for 20 IgG receptors using a high-throughput multiplexed microsphere assay. Patients with JIA exhibited an increase in hypogalactosylated and hyposialylated IgG glycans, but no change in fucosylation or bisection, together with alteration in the spectrum of IgG ligand binding. Supervised machine learning demonstrated a robust capacity to discriminate JIA subjects from controls using either glycosylation or binding data. The binding signature was driven predominantly by enhanced affinity for Fc receptor like protein 5 (FcRL5), a noncanonical Fc receptor expressed on B cells. Affinity for FcRL5 correlated inversely with galactosylation and sialylation, a relationship confirmed through enzymatic manipulation. These results demonstrate the capacity of combined structural and biophysical IgG phenotyping to define the overall functional impact of IgG glycan changes and implicate FcRL5 as a potential cellular sensor of IgG glycosylation.
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Base de dados:
MEDLINE
Assunto principal:
Artrite Juvenil
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Sítios de Ligação de Anticorpos
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Imunoglobulina G
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Fragmentos Fc das Imunoglobulinas
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Receptores Fc
Idioma:
En
Ano de publicação:
2017
Tipo de documento:
Article