POS0811 HIGH DIMENSIONAL CARTOGRAPHY OF LYMPHOCYTES USING SINGLE-CELL MASS CYTOMETRY DIFFERENTIATES SYSTEMIC LUPUS ERYTHEMATOSUS AND PRIMARY SJÖGREN`S SYNDROME

Background Autoimmune conditions such as primary Sjögren’s syndrome (pSS) and systemic lupus erythematosus (SLE) share clinical serological features characterized by IFN signature (1), autoantibody formation (2), post-activated phenotype (3) chronic inflammation. Although the 2019 SLE EULAR/ACR classification criteria facilitate a more precise discrimination between pSS (4), better understanding of distinct immunological patterns both diseases is required for developing fine-tuned immune modulations therapeutic interventions. Objectives In this study we aimed at characterizing deep phenotyping lymphocytes innate cells patients with differentiation abnormalities. Methods Peripheral PBMCs (n=21) or (n=13) well from healthy controls (HD, n=15) were isolated. stained B T/innate panel analyzed using mass cytometry. After manual pre-gating CD19+, CD3+ cells, unbiased clustering analysis was performed visualized UMAPs. Clusters identified subsequently annotated according to median expression lineage markers. Results Altogether, 13 clusters in cell, 12 cluster T cell compartment disease dependent variations frequencies marker expression. abnormalities characteristic while striking prominent pSS. IgD- CD27- double negative (DN) sub-clusters increased SLE. Among DN subsets frequency that presented lower CD19 correlated PB frequencies. A Comparison activation markers revealed CD86 on various Further, memory expressing IgA stood out higher KI-67 CD45RO patients, PD1+ ICOS+ CD4+ follicular helper CD8 effector terminal differentiated expanded. Notably, checkpoint molecules ICOS, TIGIT PD1 upregulated clusters. Finally, intermediated monocytes express CD226 reduced when compared Figure 1. Workflow characterize single-cell cytometry (Created BioRender.com ) Conclusion High dimensional characterization B, illustrated differences diseases. showed alterations consistent pathways driving these The immunologic abnormalities, SLE, might contribute monitoring selective treatment approaches. References [1]Rose T, Szelinski F, Lisney A, Reiter K, Fleischer SJ, Burmester GR, et al. SIGLEC1 biomarker activity indicates extraglandular manifestation syndrome. RMD Open. 2016;2(2):e000292. [2]Andraos R, Ahmad Eriksson P, Dahlström Ö, Wirestam L, Dahle C, Autoantibodies associated sclerosis three autoimmune imprinted type I interferon gene dysregulation: comparison across sclerosis. Lupus Science & Medicine. 2022;9(1):e000732. [3]Weißenberg SY, Schrezenmeier E, Stefanski AL, Wiedemann Rincon-Arevalo H, Identification Characterization Post-activated Cells Systemic Diseases. Front Immunol. 2019;10:2136. [4]Assan Seror Mariette X, Nocturne G. New are valuable distinguishing Annals Rheumatic 2021;80(8):e122. Acknowledgements Dr. Sebastian Fuchs. Disclosure Interests Franziska Szelinski: None declared, Ana-Luisa Stefanski: Annika Glenzer: Andreas Frei Employee of: Roche, Andreia Lino: Thomas Dörner Grant/research support from: Roche.