ACR Meeting Abstracts

ACR Meeting Abstracts

  • Meetings
    • ACR Convergence 2024
    • ACR Convergence 2023
    • 2023 ACR/ARP PRSYM
    • ACR Convergence 2022
    • ACR Convergence 2021
    • ACR Convergence 2020
    • 2020 ACR/ARP PRSYM
    • 2019 ACR/ARP Annual Meeting
    • 2018-2009 Meetings
    • Download Abstracts
  • Keyword Index
  • Advanced Search
  • Your Favorites
    • Favorites
    • Login
    • View and print all favorites
    • Clear all your favorites
  • ACR Meetings

Abstract Number: 0891

Shared and Disease-Specific Mechanisms of Autoimmunity Using Single Cell Sequencing of Peripheral Immune Cells

Jacquelyn Nestor1, Rachelly Normand1, Wamia Said1, Sergio Aguilar2, Nandini Samanta1, Sidney Martin1, Roya Best1, Hoang Anh Tran1, Adrien Antoinette1, Eilish Dillon3, Devin King3, April Jorge4, Maureen Leonard4, Pritha Sen3, Kerry Reynolds4, John Stone5, Michelle Rengarajan1, Tanuja Chitnis6, Kevin Wei7, Deepak Rao3, Andrew Luster8, Gary Reynolds1 and Alexandra-Chloe Villani1, 1Massachusetts General Hospital, Harvard Medical School, Broad Institute of MIT and Harvard, Boston, MA, 2National Center for Genomic Analysis, Barcelona, Spain, 3Brigham and Women's Hospital, Harvard Medical School, Boston, MA, 4Massachusetts General Hospital, Harvard Medical School, Boston, MA, 5Massachusetts General Hospital , Harvard Medical School, Concord, MA, 6Brigham and Women's Hospital, Massachusetts General Hospital, Harvard Medical School, Boston, MA, 7Brigham and Women's Hospital at Harvard Medical School, Boston, MA, 8Massachusetts General Hospital, Charlestown, MA

Meeting: ACR Convergence 2024

Keywords: autoimmune diseases, genomics, immunology, Inflammation, Systems-based Studies

  • Tweet
  • Click to email a link to a friend (Opens in new window) Email
  • Click to print (Opens in new window) Print
Session Information

Date: Sunday, November 17, 2024

Title: Genetics, Genomics & Proteomics Poster

Session Type: Poster Session B

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

Background/Purpose: Rheumatologic diseases are characterized by distinct clinical presentations and patterns of organ involvement, yet share many genetic risk factors and treatment responses. This suggests that although etiologies may be multifactorial, there are likely shared mechanisms across autoimmunity. Prior single cell genomic studies have predominantly been disease-specific or captured only a small subset of rheumatic diseases. The goals of this study were to identify both unique and shared mechanisms of autoimmunity across a wide-array of diseases using single-cell RNA sequencing (scRNAseq), including both tissue-specific and systemic autoimmune diseases. We also integrated patients with checkpoint inhibitor toxicities to gain insight into biological determinants driving the break of immune tolerance in de novo autoimmunity.

Methods: ScRNAseq was generated (10x Genomics) with paired surface protein (n=204 targets; CITE-seq protocol) for a minimum of 20 patients per disease: Systemic Lupus Erythematosus (SLE), Rheumatoid Arthritis, IgG4-related disease, Graves’ Disease, Hashimoto’s Disease, Multiple Sclerosis (MS), Type 1 Diabetes, Celiac Disease, and checkpoint inhibitor related diabetes and thyroiditis. Sequencing data (Illumina NovaSeq X) was aligned, processed (CellRanger V6.0.2) and integrated (Harmony). Upon defining cell subsets across lineages with iterative clustering strategies, downstream analysis focused on cellular and transcriptional programs that are shared and distinct across disease. Differential cell-type abundance was assessed by a mixed effects logistic regression model (MASC) and differentially expressed gene analysis was performed (DESeq2).

Results: We analyzed 3,542,103 cells after quality-control filtering and identified an initial set of 45 distinct cell types across lineages. Differential abundance analysis highlighted expected alterations in SLE (reduction in CD4+ T cells; expansion of B cells) while also providing greater resolution on the specific cell types involved (specific reductions in RORC+ CD4+ T cells and proliferating plasma cells). We identified novel findings such as expansion of a monocyte subset with prominent interferon signature in MS, celiac and type 1 diabetes, reduction of pDCs in IgG4-related disease, and reduction of CD4+ T cells with a Treg signature across diseases. Comparing gene expression in healthy and disease highlighted that many genes were differentially expressed in B cell subsets in Hashimoto’s and Graves’ disease ( >350 each) whereas relatively fewer were altered in checkpoint-associated thyroiditis (< 100 each), highlighting distinct biology despite similar clinical presentations. Ongoing analysis looking at gene programs and integrating cell surface protein expression, TCR and BCR sequencing will enable further definition of key drivers of autoimmunity.  

Conclusion: Our cross-disease analytical strategies enabled identification of several shared and distinct biological programs, which ultimately may help nominate novel drug targets relevant to multiple autoimmune diseases, further emphasizing the importance of cross-discipline collaborations in addition to disease-specific study.


Disclosures: J. Nestor: None; R. Normand: None; W. Said: None; S. Aguilar: None; N. Samanta: None; S. Martin: None; R. Best: None; H. Tran: None; A. Antoinette: None; E. Dillon: None; D. King: None; A. Jorge: Bristol-Myers Squibb(BMS), 12, Site investigator for a clinicl trial, Cabaletta Bio, 12, Site Sub-investigator for a clinical trial; M. Leonard: Israel Biotech Fund, 2, Moderna, 5, Takeda, 2, 5, Thermofisher, 2; P. Sen: None; K. Reynolds: CME Outfitters, 6, MedScape, 6, SAGA Diagnostics, 1; J. Stone: Amgen, 1, 2, 6, 7, Argenx, 2, Bristol-Myers Squibb(BMS), 5, Novartis, 2, 6, Sanofi, 2, Zenas, 2; M. Rengarajan: None; T. Chitnis: BrightFocus Foundation, 5, Bristol-Myers Squibb(BMS), 2, 5, Cabaletta Bio, 2, Cycle Pharmaceuticals, 2, EMD Serono, 5, F. Hoffmann-La Roche Ltd, 2, Genentech, 2, 5, I-MAB Biopharma, 5, Intellisphere, LLC, 6, Janssen, 2, Massachusetts Life Sciences Center, 5, Merck KGaA, 2, MJH Life Sciences, 2, National Institutes of Health, 5, National MS Society, 6, Novartis Pharmaceuticals, 5, Novartis Pharmaceuticals AG, 2, Novartis Pharmaceuticals KK, 2, Octave Bioscience, 2, 5, Prime Education, 6, Sanofi, 2, Sanofi Genzyme, 5, Siemens, 2, Tiziana Therapeutics, 5, UCB Biopharma, 2, US Department of Defense, 5, Wesley Clover International, 5; K. Wei: 10X Genomics, 5, Gilead sciences, 2, Merck/MSD, 5, Mestag, 2, santa ana bio, 2; D. Rao: Amgen, 6, AnaptysBio, 2, AstraZeneca, 1, Bristol-Myers Squibb, 2, 5, GlaxoSmithKline, 2, HiFiBio, 2, Janssen, 5, Merck, 5, Scipher Medicine, 2; A. Luster: None; G. Reynolds: None; A. Villani: 10x Genomics, 3, 11.

To cite this abstract in AMA style:

Nestor J, Normand R, Said W, Aguilar S, Samanta N, Martin S, Best R, Tran H, Antoinette A, Dillon E, King D, Jorge A, Leonard M, Sen P, Reynolds K, Stone J, Rengarajan M, Chitnis T, Wei K, Rao D, Luster A, Reynolds G, Villani A. Shared and Disease-Specific Mechanisms of Autoimmunity Using Single Cell Sequencing of Peripheral Immune Cells [abstract]. Arthritis Rheumatol. 2024; 76 (suppl 9). https://acrabstracts.org/abstract/shared-and-disease-specific-mechanisms-of-autoimmunity-using-single-cell-sequencing-of-peripheral-immune-cells/. Accessed .
  • Tweet
  • Click to email a link to a friend (Opens in new window) Email
  • Click to print (Opens in new window) Print

« Back to ACR Convergence 2024

ACR Meeting Abstracts - https://acrabstracts.org/abstract/shared-and-disease-specific-mechanisms-of-autoimmunity-using-single-cell-sequencing-of-peripheral-immune-cells/

Advanced Search

Your Favorites

You can save and print a list of your favorite abstracts during your browser session by clicking the “Favorite” button at the bottom of any abstract. View your favorites »

All abstracts accepted to ACR Convergence are under media embargo once the ACR has notified presenters of their abstract’s acceptance. They may be presented at other meetings or published as manuscripts after this time but should not be discussed in non-scholarly venues or outlets. The following embargo policies are strictly enforced by the ACR.

Accepted abstracts are made available to the public online in advance of the meeting and are published in a special online supplement of our scientific journal, Arthritis & Rheumatology. Information contained in those abstracts may not be released until the abstracts appear online. In an exception to the media embargo, academic institutions, private organizations, and companies with products whose value may be influenced by information contained in an abstract may issue a press release to coincide with the availability of an ACR abstract on the ACR website. However, the ACR continues to require that information that goes beyond that contained in the abstract (e.g., discussion of the abstract done as part of editorial news coverage) is under media embargo until 10:00 AM ET on November 14, 2024. Journalists with access to embargoed information cannot release articles or editorial news coverage before this time. Editorial news coverage is considered original articles/videos developed by employed journalists to report facts, commentary, and subject matter expert quotes in a narrative form using a variety of sources (e.g., research, announcements, press releases, events, etc.).

Violation of this policy may result in the abstract being withdrawn from the meeting and other measures deemed appropriate. Authors are responsible for notifying colleagues, institutions, communications firms, and all other stakeholders related to the development or promotion of the abstract about this policy. If you have questions about the ACR abstract embargo policy, please contact ACR abstracts staff at [email protected].

Wiley

  • Online Journal
  • Privacy Policy
  • Permissions Policies
  • Cookie Preferences

© Copyright 2025 American College of Rheumatology