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. 2025 Mar;77(3):311-321.
doi: 10.1002/art.43018. Epub 2024 Nov 11.

Impact of IgG Fc Glycosylation on Disease Dynamics in Patients With Primary Sjögren Disease

Helena Achten  1 , Leander Meuris  2 , Liselotte Deroo  3 , Matthias Jarlborg  4 , Tine Decruy  4 , Joke Deprez  4 , Emilie Dumas  4 , Kristel De Boeck  5 , Eva Genbrugge  5 , Wouter Bauters  5 , Frederick Dochy  5 , David Creytens  3 , Dimitri Roels  5 , Nico Callewaert  2 , Dirk Elewaut  1 , Isabelle Peene  6
Affiliations

Impact of IgG Fc Glycosylation on Disease Dynamics in Patients With Primary Sjögren Disease

Helena Achten et al. Arthritis Rheumatol. 2025 Mar.

Abstract

Objective: Glycans attached to the Fc region of IgG antibodies influence their pro- or anti-inflammatory effector function. We aimed to explore the interrelation of the Fc glycosylation profile and disease transition, disease activity, and outcome in patients with suspected and confirmed primary Sjögren disease (SjD).

Methods: IgG Fc sialylation and IgG Fc galactosylation serum levels were determined in 300 patients from the Belgian Sjögren's Syndrome Transition Trial. This cohort includes both suspected and confirmed patients with SjD meeting the 2016 American College of Rheumatology/EULAR criteria. Salivary gland involvement was evaluated through ultrasonography (Hocevar score 0-48) and histopathology (focus score). The relative amount of sialylated and galactosylated IgG was determined by capillary electrophoresis after using the endoglycosidase S-based assay.

Results: Patients with SjD exhibited significantly lower sialylation and galactosylation levels versus asymptomatic carriers of anti-SSA and patients with sicca. Lower sialylation and galactosylation levels were significantly associated with an increase in B cell activation markers and distinct autoantibody profiles, particularly with multiple autoantibody reactivities. They were also linked to histopathological salivary gland alterations, higher Hocevar scores, and, importantly, risk factors for non-Hodgkin lymphoma (NHL) development. In contrast, patients with SjD who were mono-anti-Ro60 positive and those who were anti-SSA negative had normal IgG Fc glycosylation.

Conclusion: This study points to a novel role of IgG Fc glycosylation in patients with SjD in predicting disease transition, monitoring disease activity, and stratifying risk of NHL development.

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