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Abstract Number: 4

Anti-Jo1 Positive Myositis Patients Display a Characteristic IgG Fc-Glycan Profile Which Is Further Enhanced in Anti-Jo1 Autoantibodies

Catia Fernandes-Cerqueira1,2, Nuria Renard1,2, Antonella Notarnicola1,2, Edvard Wigren1,2,3, Susanne Graslund1,2,3, Roman Zubarev4, Ingrid E. Lundberg1,2 and Susanna L. Lundström4, 1Department of Medicine, Division of Rheumatology, Karolinska Institutet, Stockholm, Sweden, 2Center for Molecular Medicine, Stockholm, Sweden, 3Structural Genomics Consortium, Stockholm, Sweden, 4Department of Medical Biochemistry and Biophysics, Division of Physiological Chemistry I, Stockholm, Sweden

Meeting: 2018 ACR/ARHP Annual Meeting

Keywords: autoantibodies, autoantigens, glycoproteins and myositis, Lung Disease

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Session Information

Date: Sunday, October 21, 2018

Session Title: B Cell Biology and Targets in Autoimmune and Inflammatory Disease Poster

Session Type: ACR Poster Session A

Session Time: 9:00AM-11:00AM

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.


Disclosure: C. Fernandes-Cerqueira, None; N. Renard, None; A. Notarnicola, None; E. Wigren, None; S. Graslund, None; R. Zubarev, None; I. E. Lundberg, Bristol-Myers Squibb, 2,AstraZeneca, 2,AstraZeneca, 5,UCB, Inc., 5,Corbus Pharmaceuticals, 5,Novartis, 1,Roche, 1; S. L. Lundström, None.

To cite this abstract in AMA style:

Fernandes-Cerqueira C, Renard N, Notarnicola A, Wigren E, Graslund S, Zubarev R, Lundberg IE, Lundström SL. Anti-Jo1 Positive Myositis Patients Display a Characteristic IgG Fc-Glycan Profile Which Is Further Enhanced in Anti-Jo1 Autoantibodies [abstract]. Arthritis Rheumatol. 2018; 70 (suppl 9). https://acrabstracts.org/abstract/anti-jo1-positive-myositis-patients-display-a-characteristic-igg-fc-glycan-profile-which-is-further-enhanced-in-anti-jo1-autoantibodies/. Accessed February 2, 2023.
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