Session Information
Date: Sunday, October 26, 2025
Title: (0506–0521) Sjögren’s Disease – Basic & Clinical Science Poster I: Etiology, Pathogenesis, Diagnosis
Session Type: Poster Session A
Session Time: 10:30AM-12:30PM
Background/Purpose: 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.
Methods: In serum at enrollment from 369 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 a 96-well ELISA plate for 1 h at 4°C. 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 (pM).
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). In multivariate analysis, taking notably anti-SSA, rs9273012 (a HLA class II gene polymporphism previously reported to be associated with serum IFN-alpha level) and clinESSDAI into account, sICs remained significantly and independently associated with serum levels of IFN-alpha(p=7,6*10-7).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 pM/L vs 88 pM/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 pM/L, 90 pM/L and 51 pM/L, respectively, p < 0.001), these 3 patient clusters defined as recently published (2). No association was observed between serum ICs and history of previous lymphoma. Ten incident lymphoma have occured since patients were enrolled in the cohort. Among patients with incident lymphoma, serum levels of sICs were significantly higher than in patient without lymphoma (225 vs 94, p=0,025)
Conclusion: Serum sICs assessed using a cell-based assay are associated with activation of type I interferon pathways, systemic disease activity, and incident lymphoma in Sjogren’s disease. References1. Chen H, et al. EMBO Mol Med 20222. Nguyen Y, et al. Lancet Rheumatol 2024
To cite this abstract in AMA style:
Pouenat C, Vierling M, Meier C, Robin L, Kolb P, Hengel H, Nocturne G, Cornec D, Devauchelle V, Le Guern V, larroche C, Sène D, Couderc M, HACHULLA E, Dieude P, Vittecoq O, Morel J, Meyer N, Seror R, Voll R, Duret P, Miguet L, Mariette X, GOTTENBERG J. Serum immune complexes assessed using a cell-reporter assay are associated with serum IFN-alpha levels, disease activity and the risk of incident lymphoma in the ASSESS prospective cohort [abstract]. Arthritis Rheumatol. 2025; 77 (suppl 9). https://acrabstracts.org/abstract/serum-immune-complexes-assessed-using-a-cell-reporter-assay-are-associated-with-serum-ifn-alpha-levels-disease-activity-and-the-risk-of-incident-lymphoma-in-the-assess-prospective-cohort/. Accessed .« Back to ACR Convergence 2025
ACR Meeting Abstracts - https://acrabstracts.org/abstract/serum-immune-complexes-assessed-using-a-cell-reporter-assay-are-associated-with-serum-ifn-alpha-levels-disease-activity-and-the-risk-of-incident-lymphoma-in-the-assess-prospective-cohort/