Open AccessMultiple juvenile idiopathic arthritis subtypes demonstrate proinflammatory IgG glycosylation
Author(s) -
Ercan Altan,
Barnes Michael G.,
Hazen Melissa,
Tory Heather,
Henderson Lauren,
Dedeoglu Fatma,
Fuhlbrigge Robert C.,
Grom Alexei,
Holm Ingrid A.,
Kellogg Mark,
Kim Susan,
Adamczyk Barbara,
Rudd Pauline M.,
Son Mary Beth,
Sundel Robert P.,
Foell Dirk,
Glass David N.,
Thompson Susan D.,
Nigrovic Peter A.
Publication year - 2012
Publication title -
arthritis & rheumatism
Language(s) - English
Resource type - Journals
eISSN - 1529-0131
pISSN - 0004-3591
DOI - 10.1002/art.34507
Subject(s) - medicine , arthritis , proinflammatory cytokine , rheumatoid arthritis , immunology , gastroenterology , inflammation
Objective Rheumatoid arthritis is associated with an excess of agalactosylated (G0) IgG that is considered relatively proinflammatory. Assessment of this association in juvenile idiopathic arthritis (JIA) is complicated by age‐dependent IgG glycan variation. The aim of this study was to conduct the first large‐scale survey of IgG glycans in healthy children and patients with JIA, with a focus on early childhood, the time of peak JIA incidence. Methods IgG glycans from healthy children and disease‐modifying antirheumatic drug–naive patients with JIA were characterized using high‐performance liquid chromatography. Agalactosylated glycans were quantitated with reference to monogalactosylated (G1) species. Associations were sought between the G0:G1 ratio and disease characteristics. Results Among healthy children ages 9 months to 16 years (n = 165), the G0:G1 ratio was highly age dependent, with the ratio peaking to 1.19 in children younger than age 3 years and declining to a nadir of 0.83 after age 10 years (Spearman's ρ = 0.60, P < 0.0001). In patients with JIA (n = 141), the G0:G1 ratio was elevated compared with that in control subjects (1.32 versus 1.02; P < 0.0001). The G0:G1 ratio corrected for age was abnormally high in all JIA subtypes (enthesitis‐related arthritis was not assessed), most strikingly in systemic JIA. Glycosylation aberrancy was comparable in patients with and those without antinuclear antibodies and in both early‐ and late‐onset disease and exhibited at most a weak correlation with markers of inflammation. Conclusion IgG glycosylation is skewed toward proinflammatory G0 variants in healthy children, in particular during the first few years of life. This deviation is exaggerated in patients with JIA. The role for IgG glycan variation in immune function in children, including the predilection of JIA for early childhood, remains to be defined.