IgG-Fc-N-Sialylation and -Galactosylation in Primary Sjögren’s Syndrome (Pss) in Its Potential as Marker of Disease State and Disease Activity

Helena Achten¹, Liselotte Deroo², Kristel De Boeck³, Matthias Jarlborg¹, Tine Decruy¹, Joke Deprez¹, Emilie Dumas¹, Dirk Elewaut⁴ and isabelle peene⁵, ¹Ghent University, Ghent, Belgium, ²Ghent University, Gent, Belgium, ³Ghent University Hospital, Ghent, Belgium, ⁴Ghent University and VIB Center for Inflammation Research, Ghent, Belgium, ⁵University Hospital Ghent, Ghent, Belgium

Meeting: ACR Convergence 2023

Keywords: Autoantibody(ies), Disease Activity, immunology, proteomics, Sjögren's syndrome

Session Information

Date: Monday, November 13, 2023

Title: Abstracts: Sjögren’s Syndrome – Basic & Clinical Science

Session Type: Abstract Session

Session Time: 2:00PM-3:30PM

Background/Purpose: Loss of galactose and sialic acid structures attached to the IgG-Fc-fragment switches the antibody effector function from anti-inflammatory to pro-inflammatory¹. This study investigated the IgG- Fc-N-glycosylation profiles in patients from the Belgian Sjögren’s Syndrome Transition Trial (BeSSTT) in relation to disease state, salivary gland ultrasonography SGUS) and histopathology, and autoantibodies against SSA (Ro52/Ro60) and SSB.

Methods: The relative amount of N-sialylated and N-galactosylated IgG was determined by capillary electrophoresis after using the endo-S glycosidase based assay. 300 serum samples of patients of the BeSSTT, an observational cohort of patients with definite pSS (n=177), fulfilling the 2016 ACR/EULAR classification criteria, and of patients with suspected pSS (n=111) due to presence of either objective sicca or one immunological criterion, were investigated. Groups were made based on the presence or absence of sicca complaints, objective sicca, anti-SSA reactivity and histopathology focus score. SGUS was assessed by Hocevar Score, categorized in negative (0-14), low positive (15-26) and high positive (27-48)². Differences in levels of IgG-Fc-N-sialylation and -galactosylation were determined using Kruskal-Wallis testing. P-values ≤0.05 were considered statistically significant. Bonferroni correction was applied for post-hoc analyses.

Results: IgG-Fc-N-sialylation and -galactosylation were significantly lower in definite pSS than in patients with sicca complaints, objective sicca or anti-SSA/SSB reactivity only (probable pSS) (Fig 1). Besides, IgG-Fc-N-sialylation and IgG-Fc-N-galactosylation were significantly lower in high positive SGUS- versus low positive and negative SGUS-scores and in positive versus negative focus scores. IgG-Fc-N-sialylation and -galactosylation were significantly lower in anti-Ro52+Ro60+SSB+, anti-Ro52+Ro60+ and anti-Ro52+ patients than in anti-SSA-/SSB- patients. Strikingly, IgG-Fc-N-sialylation and -galactosylation were also significantly higher in anti-Ro52+60+ and anti-Ro52+Ro60+SSB+patients than in anti-Ro60+ patients (Fig 2). Results are shown in Table 1.

Conclusion: There was a gradual loss of IgG-Fc-N-sialic acid and IgG-Fc-N-galactose as the disease became more prominent, as observed from sicca and probable pSS to definite pSS. The IgG-Fc-N-glycosylation profile was associated with the degree of salivary gland damage in pSS. Anti-Ro52+Ro60+SSB+, Anti-Ro52+Ro60+ and Anti-Ro52+ patients had a more pro-inflammatory IgG-Fc-N-glycosylation profile than anti-SSA- and strikingly also than anti-Ro60+ patients.

Table 1. Relative amount of Fc-N-sialylated and Fc-N-galactosylated IgG in relation to disease state, salivary gland damage (SGUS and histopathology) and autoantibody profile.

Figure 1. IgG- Fc-N-galactosylation in function of disease state

Figure 2. IgG-Fc-N-galactosylation level in function of autoantibody profile

Disclosures: H. Achten: None; L. Deroo: None; K. De Boeck: None; M. Jarlborg: None; T. Decruy: None; J. Deprez: None; E. Dumas: None; D. Elewaut: AbbVie/Abbott, 6, Bristol-Myers Squibb(BMS), 5, Eli Lilly, 2, galapagos, 5, Janssen, 6; i. peene: argenx, 1, Eli Lilly, 6, Janssen, 6.

To cite this abstract in AMA style:

Achten H, Deroo L, De Boeck K, Jarlborg M, Decruy T, Deprez J, Dumas E, Elewaut D, peene i. IgG-Fc-N-Sialylation and -Galactosylation in Primary Sjögren’s Syndrome (Pss) in Its Potential as Marker of Disease State and Disease Activity [abstract]. Arthritis Rheumatol. 2023; 75 (suppl 9). https://acrabstracts.org/abstract/igg-fc-n-sialylation-and-galactosylation-in-primary-sjogrens-syndrome-pss-in-its-potential-as-marker-of-disease-state-and-disease-activity/. Accessed .

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