POS1005 SYSTEMS SEROLOGY IDENTIFIES NOVEL AUTOANTIBODY SIGNATURES FOR SJÖGREN’S SYNDROME DIAGNOSIS
Authors: M. Killian, S. Shoffner-Beck, S. Paul, K. Arnold, A. Chung
Journal: Annals of the Rheumatic Diseases (2024)

<h3>Background:</h3> Sjögren's Syndrome (SjS) has long been associated with elevated autoantibodies to the classical autoantigens: Ro60, Ro52 and La, however, defining serostatus continues to be a challenge. Clinically these autoantibody levels are tested via ELISA, however, due to threshold requirements, testing is not always very sensitive and one third of the patients are qualified as seronegative. Hence differentiating seronegative between seronegative SjS patients and non-SjS sicca patients (with dry mouth and eye symptoms, but not qualifying for disease), present an additional diagnostic challenge. <h3>Objectives:</h3> Here we aimed to identify improved autoantibody signatures (including classical and non-classical autoantibodies, as well as novel autoantibody-related features) that distinguish between healthy individuals and patients with non-SjS sicca syndrome or SjS. <h3>Methods:</h3> Systems serology approaches were applied to 58 SjS (40 ELISA seropositive and 18 seronegative patients to classical autoantigens), 16 non-SjS sicca syndrome patients and 40 healthy individuals. Multiplex assays were used to measure antibody isotypes, subclasses, Fc Receptors (FcR) and complement engagement to 14 autoantigens. Machine learning models were used to identify unique autoantibody signatures that distinguish between healthy, non-SjS sicca or SjS individuals. <h3>Results:</h3> A seven-feature autoantibody signature, that mainly included anti-Ro60-related features (IgG, C1Q and FcR binding), accurately distinguished healthy and SjS. Cell-based assays confirmed an association between increased Ro60-specific IgG and FcR binding with Ro60-specific antibody-mediated phagocytosis. Non-SjS sicca patients could be distinguished from healthy individuals based upon an antibody signature targeting non-classical autoantigens. ELISA seronegative SjS patients also had elevated levels of autoantigens that could be identified by highly sensitive multiplex assays but were not detected via ELISA. Interestingly, all these autoantibody signatures included autoantibody –specific FcR-related features. <h3>Conclusion:</h3> Our study provides important insights into the autoantibody responses in SjS, especially regarding their specific Fc/FcγR-related effector functions, and reveals potential new diagnostic and therapeutic approaches in SjS. <h3>REFERENCES:</h3> NIL. <h3>Acknowledgements:</h3> We thank all the I GET DRY (NCT03003572; PHRC-I AURA 2016 grant) study participants, investigators and administrative staff, as well as all the blood donors for their involvement in this study. The I GET DRY study was supported by a Programme Hospitalier de Recherche Clinique Interregional AURA (PHRCI-16-006). This work was supported by a NHMRC Investigator Grant #2008092 (AWC). MK was supported by Villa M (GPM Hospitaliers), L'Institut Servier and ADPMIS research grants. <h3>Disclosure of Interests:</h3> Martin Killian Novartis (2022 &amp; 2023; &lt; 5000 Euros total), CSL Vifor (2023; &lt; 2000 Euros), AstraZeneca (2023; &lt; 1000 Euros), Suzanne Shoffner-Beck: None declared, Stephane Paul: None declared, Kelly Arnold: None declared, Amy Chung: None declared.