Background/Purpose: IgG Fc-glycans affect IgG function and are altered in autoimmune diseases and autoantibodies. Anti-histidyl tRNA synthetase autoantibodies (anti-Jo1) are frequent in myositis associated with interstitial lung disease (ILD). We tested if total IgG Fc-glycans from Jo1⁺ versus Jo1^– myositis patients and anti-Jo1-IgG showed characteristic differences, and if particular Fc-glycan features could be associated with specific clinical manifestations.

Methods: Total IgG was isolated by affinity purification from serum of 44 myositis patients (19 Jo1⁺ and 25 Jo1^–) and 24 age/sex matched healthy controls (HC). Anti-Jo1-IgG was further purified from eleven patients using a recombinant Jo1-coupled affinity column. A shotgun proteomics approach was used to profile serum-derived IgG-Fc-glycans and IgG-chain distributions. Uni- and multivariate statistics were used to find characteristics and correlate data with clinical information.

Results: A high abundance of agalactosylated IgG₁ Fc-glycans was observed in myositis patients compared to HC. Using intra-individual normalization of the main agalactosylated glycan (FA2) of IgG₁ vs FA2-IgG₂, myositis and HC were distinguished with an area under the curve (AUC) of 79±6%. For Jo1⁺ the AUCs went up to 88±6%. Bisected and afucosylated Fc-glycans were significantly lower in Jo1⁺ compared to Jo1^– patients. Anti-Jo1 IgG contained even lower abundance of bisected, afucosylated and galactosylated forms compared to matched total IgG. ASS and ILD diagnosis correlated with the Jo1⁺ characteristic Fc-glycan features via multivariate analysis.

Conclusion: The anti-Jo1⁺ patient IgG Fc-glycan profile contains phenotype specific features which may underlie the pathogenic role of Jo1 autoantibodies.

ACR Meeting Abstracts - https://acrabstracts.org/abstract/anti-jo1-positive-myositis-patients-display-a-characteristic-igg-fc-glycan-profile-which-is-further-enhanced-in-anti-jo1-autoantibodies/