Association of serum IgG glycosylation with disease activity of anti-transcription intermediary factor 1 gamma positive dermatomyositis

Objective Dermatomyositis (DM) is an idiopathic inflammatory myopathy characterised by the presence of a variety of myositis-specific autoantibodies (MSA) in the circulation. As one of the commonly-detected MSA, anti-transcription intermediary factor 1 gamma (TIF1 gamma) autoantibody is strongly associated with DM-related malignancy and disease activity. We investigated the glycosylation patterns of serum IgG and to determine the clinical significance of specific glycosylation patterns in patients with anti-TIF1 gamma positive DM.Methods Lectin microarray was used to reveal the glycosylation patterns of serum IgG among 52 DM, 46 disease controls (DC) and 49 healthy controls (HC). Lectin blot was used to further validate the specific alteration of glycosylation. The correlation between glycan levels and clinical features was also evaluated.Results The results of lectin microarray showed that compared with the DC group, the DM group had significantly lower glycan levels of mannose and glucose. Compared with the HC group, the glycans levels of GalNAc, galactose, Gal beta 3GalNAc, sialic acid, and fucose were observed significantly higher in DM group. Lectin blot demonstrated that anti-TIF1 gamma positive DM had lower glycan level of GlcNAc (recognised by LEL) compared to patients with MSA negative DM, DC, and HC groups. Additionally, the glycan level of GlcNAc was positively associated with manual muscle test (r=0.547, p=0.028), or negatively associated with IL-6 level (r=-0.756, p=0.049) and disease activity score (r=-0.507, p=0.045).Conclusion Anti-TIF1 gamma positive DM presents a unique glycosylation pattern in serum IgG. Considering that the glycan level of GlcNAc reflects the inflammatory state and disease activity, glycosylation has a role in clinical utility by monitoring disease in patients with anti-TIF1 gamma positive DM.