Background: Fc‐gamma receptor (FcγR) activation by soluble IgG immune complexes (sICs) is considered to play a pivotal pathogenic role in B-cell-mediated autoimmune diseases, such as primary Sjögren’s disease (SD). Previous indirect ELISA assays based on the affinity of sICs to C1q or C3d, were not sensitive enough and did not allow a correct discrimination between IgG monomers and sICs.

Objectives: A direct, sensitive and robust assay allowing the detection of sICs has not been evaluated in SD. Using a cell-reporter assay, we assessed the relevance of sICs in a prospective cohort of patients with SD.

Methods: In serum at enrollment from 368 patients with primary SD prospectively followed up since 2005, FcγR activation was measured. Briefly, reporter cells transfected with human-FcγRIIA were incubated with patient’s serum [1]. Incubation was performed in 96-well ELISA plate previously saturated with PBS 10% FBS for 1h at 4°. Reporter-cell IL-2 secretion was quantified after 20 h of incubation using ELISA. The area under curve (AUC) of IL2 secretion was compared to that resulting from incubation of synthetic ICs (hTNFa with infliximab) to obtain an equivalent quantification.

Results: Serum levels of sICs were significantly correlated with serum levels of IFN-alpha assessed by digital ELISA (r=0,5; p= 2.5*10 ^-19 ), rheumatoid factor (r=0.43, p= 1.95*10 ^-18 ), and of quantitative levels of anti-SSA (r=0.35, 6.1*10 ^-12 ) and anti-SSB (r=0.34, 5.0*10 ^-11 ). Serum levels of sICs were higher in patients with low C4 and T CD4 lymphocytopenia (p= 0.008 and p= 0.004, respectively). Median serum levels of sICs were higher in patients with moderate or high systemic disease activity (ESSDAI≥5) at enrolment than in patients with no or low systemic disease activity (ESSDAI<5) (121 pmol/L vs 88 pmol/L, p= 0.03). Median serum levels of sICs were higher in patients with B cell activation markers and no systemic disease activity or in patients with moderate to severe systemic disease activity than in patients with high symptom burden and no systemic disease activity (121 pmol/L, 90 pmol/L and 51 pmol/L, respectively, p< 0.001), these 3 patient clusters defined as recently published [2]. No significant association was observed with lymphoma.

Conclusion: Serum sICs assessed using a cell-based assay are associated with activation of type I interferon pathways, markers of B-cell activation and systemic disease activity in Sjogren’s disease.

REFERENCES: [1] Chen H, et al. EMBO Mol Med 2022.

[2] Nguyen Y, et al. Lancet Rheumatol 2024.

Acknowledgements: NIL.

Disclosure of Interests: None declared.

© The Authors 2025. This abstract is an open access article published in Annals of Rheumatic Diseases under the CC BY-NC-ND license ( http://creativecommons.org/licenses/by-nc-nd/4.0/ ). Neither EULAR nor the publisher make any representation as to the accuracy of the content. The authors are solely responsible for the content in their abstract including accuracy of the facts, statements, results, conclusion, citing resources etc.