Rheumatoid arthritis is associated with an excess of hypogalactosylated (G0) IgG that is considered relatively pro-inflammatory. Assessment of this association in juvenile idiopathic arthritis (JIA) is complicated by age-dependent IgG glycan variation. We undertook the first large-scale survey of IgG glycans in normal children and in patients with JIA, with a focus on early childhood, the time of peak JIA incidence.
IgG glycans from healthy children and DMARD-naïve JIA patients were characterized using high-performance liquid chromatography (HPLC). Pro-inflammatory G0 glycans were quantitated with reference to monogalactosylated (G1) species. Associations were sought between G0/G1 and disease characteristics.
Among healthy children aged 9 months-16 years (n=165), G0/G1 was highly age-dependent, peaking in children <3 years old at 1.19 and declining to a nadir of 0.83 after age 10 years (Spearman ρ=0.60, p<0.0001). In patients with JIA (n=141), G0/G1 was elevated compared with controls (G0/G1 1.32 vs. 1.02, p<0.0001). Corrected for age, G0/G1 was abnormally high in all JIA subtypes (enthesitis-related arthritis not assessed), most strikingly in systemic JIA. Glycosylation aberrancy was comparable in patients with or without ANA and in both early- and late-onset disease, and exhibited at most a weak correlation with inflammatory markers.
IgG glycosylation is skewed toward pro-inflammatory 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.