POS0352 NOVEL AUTOANTIBODIES FOR THE IDENTIFICATION OF SERONEGATIVE SJÖGREN’S SYNDROME PATIENTS
Authors: F. Engelke, P. Budde, S. De Vita, T. Dörner, D. Ernst, J. Gras, H. Heidecke, A. L. Kilian, K. Kniesch, A. S. Lindemann, J. Ritter, B. Seeliger, H. D. Zucht, T. Witte
Journal: Annals of the Rheumatic Diseases (2024)

<h3>Background:</h3> Primary Sjögren's Syndrome (pSS) is a chronic, heterogeneous autoimmune disease with dysfunction of the salivary and lachrymal glands and extraglandular organ manifestations. Currently, diagnosing pSS in patients with dryness of the glands is mostly based on the presence of serological markers (Ro/SSA and La/SSB), which were found in 40-68% of patients with pSS. Diagnosing pSS in Ro/SSA negative patients is far more challenging and relies on the histological evidence of lymphocyte foci in biopsies of salivary glands or on salivary gland ultrasound. There is an interest in novel autoantibodies that can be used for the identification of Ro/SSA negative patients, and that may predict organ involvement or treatment outcome. <h3>Objectives:</h3> We aimed to identify novel autoantibodies associated with pSS, in particular with the Ro/SSA negative subset and with its organ manifestations. <h3>Methods:</h3> PSS-specific IgG and IgA autoantibody reactivity of 82 novel autoantibodies, selected in a discovery phase based on large Luminex bead-based antigen arrays, as well as 7 previously published candidates were examined in a validation cohort of 347 pSS patients, 136 patients with other rheumatic diseases and 123 healthy controls. IgG autoantibodies against the muscarinic receptor M3 and M5 (not measured in the discovery phase) were additionally investigated in the validation step by means of ELISA. <h3>Results:</h3> Autoantibody reactivity against 70 of the 82 novel preselected autoantibodies was confirmed (p≤0.05) and each of the 70 novel autoantibodies were found in up to 26% of pSS patients. Random forest classification was executed to develop a biomarker panel for diagnostic prediction of patients without antibodies against Ro/SSA, resulting in a panel of eight markers: anti-BTBD7, anti-CCL4, anti-M5, anti-HNRNPA1, anti-KDM6B, anti-TMPO, anti-TONSL and anti-OAS3. This panel identified 53% of pSS patients without Ro/SSA autoantibodies, demonstrating an area under the curve of 0.85 (95% CI 0.72 to 0.97) with a sensitivity of 73%, a specificity of 94%, and a diagnostic accuracy of 82.5%. Reactivity of autoantibodies was associated with clinical disease manifestations, such as pulmonary involvement. <h3>Conclusion:</h3> Several novel autoantibodies in patients with pSS were discovered in this study. This shows the potential of additional autoantibodies to improve diagnostic procedures of these patients, especially in patients without antibodies against Ro/SSA. <h3>REFERENCES:</h3> <b>NIL.</b> <h3>Acknowledgements:</h3> Funded by the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) under Germany's Excellence Strategy - EXC 2155 - project number 390874280. <h3>Disclosure of Interests:</h3> Fiona Engelke: None declared, Petra Budde: None declared, Salvatore De Vita: None declared, Thomas Dörner: None declared, Diana Ernst: None declared, Jan Gras: None declared, Harald Heidecke: None declared, Annika Loredana Kilian: None declared, Katja Kniesch: None declared, Ann-Sophie Lindemann: None declared, Jacob Ritter: None declared, Benjamin Seeliger Lecturing Fees Boehringer Ingelheim, GSK, IMP for a study funded by non-pharmaceutical entities (Astra Zeneca), Hans-Dieter Zucht: None declared, Torsten Witte Abbvie, UCB, Novartis, Janssen, Chugai, Roche, Amgen, Astra Zeneca, Medac, Takeda, GSK, Boehringer Ingelheim, Abbvie, UCB, Novartis, Janssen, Fresenius, Boehringer Ingelheim, Abbvie, Novartis, Takeda.