Background/Purpose:

Aberrant glycosylation of IgG is an abnormality of humoral immunity in patients with rheumatoid arthritis (RA) and juvenile idiopathic arthritis (JIA) that is not well understood. We examined the association between aberrant IgG glycosylation and clinical and laboratory parameters in JIA.

Methods:

Sera from 100 JIA patients (32 IgM rheumatoid factor (RF)-negative polyarticular, 31 oligoarticular, 23 IgM RF-positive polyarticular, 11 systemic-onset, 3 psoriatic), 29 RA patients, and 27 healthy individuals were collected. Aberrant serum IgG glycan content was measured by ELISA in all sera samples. The positive cut-off point was OD>0.31 for aberrant IgG glycan levels. Anti-cyclic citrullinated peptide (anti-CCP) antibody and RF isotypes were also measured by ELISA. Patient records were evaluated for clinical and laboratory associations, including disease activity, erythrocyte sedimentation rate (ESR) and C-reactive proteins (CRP) levels.

Results:

Forty-six (46%) JIA patients, 16 (55.2%) RA patients and 4 (14.8%) healthy individuals had elevated aberrant IgG glycan levels. Aberrant glycosylation of IgG was confirmed in JIA patients as compared with healthy individuals (OD=0.342 ± 0.213 versus OD=0.179 ± 0.110; p<0.001). Systemic-onset JIA patients demonstrated higher levels of aglycosylated IgG (OD=0.395 ±0.218) than other JIA subtypes and occurred more frequently in this subtype (54.5%). No significant difference in aberrant glycosylation of IgG was noted between JIA and RA patients (OD=0.319 ± 0.159; p=0.588). A significant correlation between aberrant IgG glycosylation and disease activity was noted in JIA patients (r=0.32, p=0.001), with aberrant IgG glycan levels significantly increased in patients with active disease (OD=0.35 ± 0.17) compared with asymptomatic patients (OD=0.23 ± 0.07) (p=0.024). This correlation was also present when looking at only the female JIA population (r=0.31, p=0.004), while no significant correlation was found in the male JIA population. Aglycosylated IgG correlated significantly with disease activity markers (ESR: r=0.47, p<0.001 and CRP: r=0.46, p<0.001) in JIA. Levels of ESR and CRP were significantly raised in JIA patients with increased aberrant IgG glycan levels (35±29 mm/hr and 2.2±2.4 mg/dl, respectively) compared to patients with normal levels (18±26 mm/hr and 0.91±1.45 mg/dl, respectively) (p<0.05). No association was found between anti-CCP antibody and RF isotypes and aberrant IgG glycosylation in JIA.

Conclusion:

Aberrant IgG glycosylation was evident in all JIA subtypes included in this study, with the highest frequency and levels found in systemic-onset JIA patients. We have shown that IgG glycan aberrancy is strongly associated with disease activity in JIA patients. This correlation was also significant when only evaluating the female JIA patients, indicating a possible hormonal influence in IgG glycosylation regulation.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/aberrant-igg-glycosylation-is-associated-with-active-disease-in-juvenile-idiopathic-arthritis-patients/