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Abstract Number: 1426

Single Cell RNA-Seq Characterization of Circulating Immune Cells in Sjogren’s Syndrome: Comparison to SLE and Rheumatoid Arhtritis

Alejandro Gomez-Gomez1, yolanda Guillen2, Paloma Vela Casasempere3, María Paula álvarez Hernández4, Ignacio Brana Abascal5, Mónica Fernández Castro6, Maria López Lasanta1, José María Pego-Reigosa7, Carlos Marras8, María García-Villanueva9, Francisco Blanco10, Patricia Carreira11, Carolina Perez-Garcia12, Íñigo Rúa-Figueroa13, Hugo F Avalos bogado1, Natalia Boix Martí1, Eric Kirkegaard-Biosca14, iago álvarez Sáez15, Nuria Palau16, Raül Tortosa16, Jesús Tornero Molina17, Antonio Fernandez Nebro18, Jaime Calvo-Alén19, Juan Cañete20, Damiana Alvarez-Errico2, Ernest Choy21, Holger Heyn22, Antonio Julia23, Sara Marsal barril1 and Jose Luis Andreu24, and on behalf of SSAD and DocTIS consortia, 1Hospital Universitari Vall d´Hebron, Rheumatology, Barcelona, Spain, 2Imidomics, Inc, Barcelona, Spain, 3Hospital General Universitario de Alicante , Rheumatology, Alicante, Spain, 4Hospital universitario de la Princesa. IIS-Princesa, Rheumatology, Madrid, Madrid, Spain, 5Hospital Universitario Central de Asturias, Oviedo, Asturias, Spain, 6Hospital Universitario Puerta de Hierro Majadahonda., Madrid, Madrid, Spain, 7Galicia Health Service (SERGAS), Vigo, Spain, 8Hospital Clínico Universitario Virgen de la Arrixaca, Murcia, Murcia, Spain, 9Hospital Ramón y Cajal, MADRID, Madrid, Spain, 10Complejo Hospitalario Universitario de A Coruña , Rheumatology, A Coruña, Spain, 11Hospital Universitario 12 de Octubre, Madrid, Madrid, Spain, 12Hospital del Mar, Barcelona, Spain, 13Department of Rheumatology, Hospital Universitario Doctor Negrín, Las Palmas de Gran Canaria, Las Palmas GC, Spain, 14Hospital Universitari Vall d´Hebron, Ophtalmology, Barcelona, Spain, 15Hospital Universitari Vall d´Hebron, Maxillofacial Surgery, Barcelona, Spain, 16Vall d´Hebron Hospital Research Institute, Rheumatology, Barcelona, Spain, 17Sociedad Española de Reumatologia, Rheumatology, Madrid, Spain, 18Hospital Regional Universitario Carlos Haya , Rheumatology, Málaga, Spain, 19Department of Rheumatology, Hospital Araba, Vitoria, Pais Vasco, Spain, 20Hospital Clinic an IDIBAPS, Barcelona, Spain, 21Cardiff University School of Medicine, Cardiff, United Kingdom, 22Centre for Genomic Regulation (CNAG-CRG), National Centre for Genomic Analysis, Barcelona, Spain, 23Vall d'Hebron Hospital Research Institute, Barcelona, Spain, 24Hospital Universitario Puerta de Hierro Majadahonda., Majadahonda, Spain

Meeting: ACR Convergence 2024

Keywords: interferon, Sjögren's syndrome

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Session Information

Date: Sunday, November 17, 2024

Title: Sjögren's Syndrome – Basic & Clinical Science Poster I

Session Type: Poster Session B

Session Time: 10:30AM-12:30PM

Background/Purpose: Primary Sjögren’s Syndrome (pSS) shares with SLE and RA features including their predominance in women, immunological characteristics and genetic risk background. Hence, to dissect the heterogeneity across these IMIDs is key to design precision medicine strategies. Single cell transcriptomics allows to interrogate patients’ samples at great resolution to inform on common and specific pathogenic molecular mechanisms that drive disease. This is relevant not only for the discovery of potentially actionable targets, but also to identify patients likely to benefit from such novel therapeutic interventions. Despite pathogenic mechanisms can be organ-specific, immune cells are mobilized via peripheral blood initiating inflammatory responses. In that respect, the profiling of peripheral blood mononuclear cells (PBMCs) is important since PBMCs may show cell-type signatures that can define disease specific pathogenesis, with the advantage of being an easily accessible tissue.

Methods: PBMCs from 8 pSS and 5 healthy donors (H)  were isolated in Ficoll gradient, and processed with Chromium Single Cell 3’ kit v3 (10X Genomics). A median of 8,008 cells per sample were profiled. Raw sequences were demultiplexed and mapped against the genome using Cell Ranger. Downstream analyses, including QC filtering, normalization, and integration were done with Seurat. Immune cell were automatically annotated using Azimuth. Single cell data from 6 RA patients (71,224 cells) and 8 SLE patients (71,224 cells), was obtained from the DoCTIS Consortium project.

Results: Differential cell abundance analysis of PBMCs among the 4 groups (H, pSS, SLE and RA) showed a significant increment in the CD8 lymphocyte population with CD8TEM features, that is specific to pSS. In turn, lower numbers of CD8 naïve T cells were observed in pSS compared to healthy individuals, a change also found in RA but not in SLE. Gene expression analysis revealed that CD14+ monocytes show the highest number of differentially expressed genes (DEGs) in pSS compared to controls. Analysis of these DEGs in CD14+ monocytes from SLE and RA patients showed a significant antagonism, with many genes showing a differential expression in the opposite direction. Second to monocytes, CD4TCM lymphocytes showed also a large number of significant DEGs between pSS patients and controls, but no significant antagonism was found in CD4TCM from RA or SLE. Pathway analysis of the genes exclusive to pSS (i.e. differentially expressed in pSS but not in SLE or RA), identified an association with the regulation of type I interferon and tumor necrosis factor production. Among the former, the family of genes encoding 2′–5′ oligoadenylate synthetases (OAS1 to OAS3) were found to be significantly overexpressed in CD14+ monocytes. OAS1 is a well-known risk gene for pSS associated at a genome-wide level.

Conclusion: We have mapped PBMCs from pSS and compared it with HC as well as SLE and RA, covering a total of 241,841 cells, providing a valuable resource for further in depth analysis. Our study reveals relevant disorder and cell-specific transcriptomic changes such as the upregulation of OAS family of IFNI response genes in CD14+ monocytes providing further clues into the mechanisms driving the disease.


Disclosures: A. Gomez-Gomez: None; y. Guillen: None; P. Vela Casasempere: None; M. álvarez Hernández: None; I. Brana Abascal: None; M. Fernández Castro: None; M. López Lasanta: None; J. Pego-Reigosa: AstraZeneca, 1, 6, GSK, 5, 6, Otsuka, 1, Pfizer, 5, Roche, 1; C. Marras: None; M. García-Villanueva: None; F. Blanco: None; P. Carreira: None; C. Perez-Garcia: None; Í. Rúa-Figueroa: AstraZeneca, 2, 6, GlaxoSmithKlein(GSK), 2, 6, Otsuka, 2, 6; H. Avalos bogado: None; N. Boix Martí: None; E. Kirkegaard-Biosca: None; i. álvarez Sáez: None; N. Palau: None; R. Tortosa: None; J. Tornero Molina: None; A. Fernandez Nebro: None; J. Calvo-Alén: None; J. Cañete: None; D. Alvarez-Errico: None; E. Choy: AbbVie, 2, 6, Amgen, 2, 6, Bio-Cancer, 5, Biocon, 2, Biogen, 2, 5, Bristol-Myers Squibb(BMS), 6, Chugai, 2, 6, Eli Lilly, 2, 6, Fresenus Kabi, 2, 6, Galapagos, 6, Gilead, 2, 6, Janssen, 2, Novartis, 2, 5, 6, Pfizer, 2, 5, 6, Regeneron, 2, 6, Roche, 2, 6, RPharm, 2, 6, Sanofi, 2, 5, 6, UCB Pharma, 6; H. Heyn: Mirxes, 2, Moderna, 2, Nanostring, 2, Omniscope, 2, 8, Singularity, 2; A. Julia: None; S. Marsal barril: None; J. Andreu: None.

To cite this abstract in AMA style:

Gomez-Gomez A, Guillen y, Vela Casasempere P, álvarez Hernández M, Brana Abascal I, Fernández Castro M, López Lasanta M, Pego-Reigosa J, Marras C, García-Villanueva M, Blanco F, Carreira P, Perez-Garcia C, Rúa-Figueroa Í, Avalos bogado H, Boix Martí N, Kirkegaard-Biosca E, álvarez Sáez i, Palau N, Tortosa R, Tornero Molina J, Fernandez Nebro A, Calvo-Alén J, Cañete J, Alvarez-Errico D, Choy E, Heyn H, Julia A, Marsal barril S, Andreu J. Single Cell RNA-Seq Characterization of Circulating Immune Cells in Sjogren’s Syndrome: Comparison to SLE and Rheumatoid Arhtritis [abstract]. Arthritis Rheumatol. 2024; 76 (suppl 9). https://acrabstracts.org/abstract/single-cell-rna-seq-characterization-of-circulating-immune-cells-in-sjogrens-syndrome-comparison-to-sle-and-rheumatoid-arhtritis/. Accessed .
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