Abstract
IgG Fc-glycans affect IgG function and are altered in autoimmune diseases and autoantibodies. Anti-histidyl tRNA synthetase autoantibodies (anti-Jo1) are frequent in patients with idiopathic inflammatory myopathies (IIM) and anti-synthetase syndrome (ASS) with associated interstitial lung disease (ILD). Thus, we hypothesized that the total-IgG Fc-glycans from Jo1(+) versus Jo1(-) patients and anti-Jo1-IgG would show characteristic differences, and that particular Fc-glycan features would be associated with specific clinical manifestations. By proteomics based mass spectrometry we observed a high abundance of agalactosylated IgG(1) Fc-glycans in ASS/IIM patients (n = 44) compared to healthy age matched controls (n = 24). Using intra-individual normalization of the main agalactosylated glycan (FA2) of IgG(1) vs FA2-IgG(2), ASS/IIM and controls were distinguished with an area under the curve (AUC) of 79 ± 6%. For Jo1(+) patients (n = 19) the AUCs went up to 88 ± 6%. Bisected and afucosylated Fc-glycans were significantly lower in Jo1(+) compared to Jo1(-) patients. Anti-Jo1-IgG enriched from eleven patients contained even significantly lower abundances of bisected, afucosylated and galactosylated forms compared to matched total-IgG. ASS and ILD diagnosis, as well as lysozyme and thrombospondin correlated with Jo1(+) characteristic Fc-glycan features. These results suggest that the anti-Jo1(+) patient Fc-glycan profile contains phenotype specific features which may underlie the pathogenic role of Jo1 autoantibodies.