Spatial Multi-omics Demonstrates Shared Immune States Across Autoimmune Diseases and Target Tissues in the Accelerating Medicines Partnership: Autoimmune and Immune-Mediated Diseases Network (AMP AIM)

Caleb Marlin¹, Roopa Madhu², Erin Theisen³, Liz Bradshaw⁴, Ce Gao⁵, Thomas Eisenhaure⁶, Nicolas Sugiarto⁷, Accelerating Medicines Partnertship: Autoimmune and Immune Mediated Diseases⁸, Jill Buyon⁹, Michelle Petri¹⁰, Brad Rovin¹¹, Victoria Werth¹², Ellen M. Gravallese¹³, Jennifer Anolik¹⁴, Larry Moreland¹⁵, Laura Donlin¹⁶, Christopher Ritchlin¹⁷, Jose Scher¹⁸, Johann Gudjonsson¹⁹, Wilson Liao²⁰, Alexis Ogdie²¹, Caroline Shiboski²², A. Darise Farris¹, Alan Baer²³, Blake M. Warner²⁴, Jose Clemente²⁵, Adriana Heguy²⁶, Michael Brenner²⁷, Nir Hacohen²⁸, Joel Guthridge¹, Judith James¹, Soumya Raychaudhuri²⁹, Lam Tsoi¹⁹, Xiang Zhou³⁰, Joshua Welch³⁰, Rachael Clark³, ilya Korsunsky²⁹, Christopher Lessard¹ and Kevin Wei³¹, ¹Oklahoma Medical Research Foundation, Oklahoma City, OK, ²Brigham and Women's Hospital, Brookline, MA, ³Brigham and Women's Hospital, Boston, ⁴Oklahoma Medical Research Foundation, Oklahoma City, ⁵Division of Rheumatology, Inflammation and Immunity, DOM, BWH; Harvard Medical School, Boston, MA, ⁶Broad Institute, Cambridge, MA, ⁷Broad Institute, Boston, ⁸Multiple Institutions, Oklahoma City, ⁹NYU Grossman School of Medicine, New York, NY, ¹⁰Johns Hopkins University School of Medicine, Timonium, MD, ¹¹The Ohio State University, Columbus, OH, ¹²University of Pennsylvania, Wynnewood, PA, ¹³Brigham and Women's Hospital, Harvard Medical School, Chestnut Hill, MA, ¹⁴University of Rochester Medical Center, Rochester, NY, ¹⁵University of Colorado, Denver, CO, ¹⁶Hospital for Special Surgery, New York, NY, ¹⁷University of Rochester Medical Center, Canandaigua, NY, ¹⁸New York University School of Medicine, New York, NY, ¹⁹University of Michigan, Ann Arbor, MI, ²⁰UCSF, San Francisco, CA, ²¹Department of Medicine, Perelman School of Medicine at the University of Pennsylvania, Wilmington, DE, ²²University of California San Francisco, San Francisco, CA, ²³Johns Hopkins University School of Medicine, Baltimore, MD, ²⁴National Institutes of Health, Bethesda, MD, ²⁵Icahn School of Medicine at Mount Sinai, New York, NY, ²⁶NYU Grossman School of Medicine, New York, ²⁷Brigham and Women's Hospital, Harvard Medical School, Newton, MA, ²⁸Broad Institute of MIT Harvard, Cambridge, MA, ²⁹Brigham and Women's Hospital, Boston, MA, ³⁰University of Michigan, Ann Arbor, ³¹Brigham and Women's Hospital at Harvard Medical School, Boston, MA

Meeting: ACR Convergence 2025

Keywords: autoimmune diseases, Psoriatic arthritis, rheumatoid arthritis, Sjögren's syndrome, Systemic lupus erythematosus (SLE)

Session Information

Date: Tuesday, October 28, 2025

Title: (2227–2264) Rheumatoid Arthritis – Diagnosis, Manifestations, and Outcomes Poster III

Session Type: Poster Session C

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

Background/Purpose: Autoimmune diseases affect more than 23.5 million Americans involving nearly every organ system of the human body. To identify shared, unique, and novel pathways underlying the pathogenesis of common autoimmune diseases, The Accelerating Medicines Partnership: Autoimmune and Immune-Mediated Diseases Network (AMP AIM) was launched to investigate Rheumatoid Arthritis (RA), Systemic Lupus Erythematosus (SLE), Psoriatic Disease (PsD), and Sjogren’s Disease (SD) using single-cell and spatial technologies.

Methods: The Disease Teams, Technology Cores, System Biology Groups, Tissue Research Center, and Research Management Units collaborated on pilot projects to evaluate spatial and single-cell technologies for their feasibility, sensitivity, and scalability. These assessments aimed to inform the selection of omics approaches that would provide the greatest utility and reproducibility across the network’s diverse research settings.

Results: Following two years of focused investigation, the AMP AIM network developed a standard operating procedure which enables a multi-institutional, spatial multi-omics workflow of deep phenotyping of study participants. This protocol leverages centrally collected, FFPE-preserved target tissues (e.g., synovium, skin, salivary gland, and kidney) and integrates spatial transcriptomics (ST) using Xenium (10x Genomics), histological evaluation via H&E staining, and protein-level spatial profiling with Imaging Mass Cytometry (IMC) on the Hyperion platform (Standard BioTools), all on the same slide.1. Successful implementation of combined spatial transcriptomics and proteomics. With the network selecting Xenium as the preferred ST platform and post-run H&E stain, we developed a workflow which integrates Xenium and IMC from the same tissue section. This results in a unified dataset comprising ~5,000 spatially resolved transcripts, 40 protein markers, and histological context, enabling single-cell level correlation of gene and protein expression within intact tissue architecture (Fig 1).2. Defining shared immune cell states in target tissues across RA, SLE, PSD, and SD. To identify shared immune cell states across autoimmune diseases and target tissues, we implemented a computational pipeline for robust cell type and state annotation in spatial transcriptomic datasets. To evaluate the generalizability of this pipeline, we used a unified scRNA-seq reference to annotate T and NK cell states across spatially profiled tissues. This approach identified 9 distinct T cell states (Fig 2A), each exhibiting comparable transcriptional signatures across RA, SLE, PSD, and SD.

Conclusion: This integrated spatial multi-omics platform is being applied across disease-specific (e.g., RA, SLE, PSD, and SD) and cross-disease studies to uncover shared and distinct cellular programs in autoimmune pathogenesis. Through robust, high-resolution, single cell analyses within the tissue context, our approach lays the foundation for discovering common and unique mechanisms and advancing targeted therapeutics across autoimmune diseases.

Figure 1: Spatial Characterization of Target Tissues. Representative images from all four target tissues (Synovium, Kidney, Salivary Gland, and Skin) processed and imaged on the Xenium spatial transcriptomics (10X Genomics), stained and whole slide imaged for H&E, and then stained and imaged for ~40 surface proteins via Imaging Mass Cytometry (Standard Biotools), all on the same tissue section and slide. Similar cell types (IMC) or transcripts (Xenium) are highlighted in the example projections to demonstrate agreement across technologies.

Figure 2: Assessment of Spatial Transcriptomics Technologies demonstrates shared T-cell states across tissues. (A) Median abundance of T-cell states, shown as the proportion relative to the number of T-cells within each tissue. (B-E) Spatial localization of T-cell states within selected regions of interest. in: (B) skin, (C) salivary gland, (D) synovium, and (E) kidney tissues. T-cells are colored by their state, and non-T-cells are colored in grey.

Disclosures: C. Marlin: None; R. Madhu: None; E. Theisen: None; L. Bradshaw: None; C. Gao: None; T. Eisenhaure: None; N. Sugiarto: None; A. Autoimmune and Immune Mediated Diseases: None; J. Buyon: Artiva Biotherapeutics, 2, Biogen, 2, Bristol-Myers Squibb(BMS), 2, Celgene, 2, CLIMB Bio Operating, 2, GlaxoSmithKlein(GSK), 2, Janssen, 2, Related Sciences, 2, UCB, 2; M. Petri: Amgen, 2, AnaptysBio, 2, Annexon Bio, 2, AstraZeneca, 2, 5, Atara Biosciences, 2, Aurinia, 2, 5, Autolus, 2, Bain Capital, 2, Baobab Therapeutics, 2, Biocryst, 2, Biogen, 2, Boxer Capital, 2, Cabaletto Bio, 2, Caribou Biosciences, 2, CTI Clinical Trial and Consulting Services, 2, CVS Health, 2, Dualitybio, 2, Eli Lilly, 2, 5, EMD Serono, 2, Emergent, 2, Escient Pharmaceuticals, 2, Exagen, 5, Exo Therapeutics, 2, Gentibio, 2, GlaxoSmithKlein(GSK), 2, 5, iCell Gene Therapeutics, 2, Innovaderm Research, 2, IQVIA, 2, Janssen, 5, Kezar Life Sciences, 2, Kira Pharmaceuticals, 2, Nexstone Immunology, 2, Nimbus Lakshmi, 2, Novartis, 2, Ono Pharma, 2, PPD Development, 2, Proviant, 2, Regeneron, 2, Seismic Therapeutic, 2, Senti Biosciences, 2, Sinomab Biosciences, 2, Steritas, 2, Takeda, 2, Tenet Medicines, 2, TG Therapeutics, 2, UCB, 2, Variant Bio, 2, Worldwide Clinical Trials, 2, Zydus, 2; B. Rovin: Alexion, 2, Artiva, 2, 11, AstraZeneca, 2, Aurinia, 2, 5, Biogen, 2, 5, Bristol Myers Squibb, 2, Cabelleta, 2, Century, 2, F. Hoffman-La Roche Ltd/Genentech, Inc., 2, GlaxoSmithKlein(GSK), 2, Novartis, 2; V. Werth: AbbVie/Abbott, 2, Amgen, 2, 5, Anaptysbio, 2, Argenx, 2, 5, AstraZeneca, 2, 5, Biogen, 2, 5, Boehringer-Ingelheim, 2, Bristol-Myers Squibb(BMS), 2, Cabaletta Bio, 2, Calyx, 2, CSL Behring, 5, Cugene, 2, Eli Lilly, 2, EMD Serona, 2, 2, Evommune, 2, Gilead, 2, 5, GlaxoSmithKlein(GSK), 2, Horizon, 5, Immunovant, 2, Janssen, 2, Kwoya Kirin, 2, Merck/MSD, 2, Novartis, 2, Nuvig, 2, Pfizer, 2, 5, Regeneron, 2, 5, Roche, 2, Rome Pharmaceuticals, 5, Sanofi, 2, Takeda, 2, UCB, 2, 2, Ventus, 2, Viela, 5; E. Gravallese: Beam Therapeutics, 11, CRISPR Therapeutics, 11, Editas Medicine, 11, Elsevier, 9, Ginkgo Bioworks, 11, Intellia Therapeutics, 11, New England Journal of Medicine, 1, UpToDate, 9; J. Anolik: None; L. Moreland: None; L. Donlin: Bristol-Myers Squibb (BMS), 2, Karius, Inc., 5, Stryker, 2; C. Ritchlin: AbbVie, 2, Amgen, 2, Bristol-Myers Squibb(BMS), 2, Eli Lilly, 2, Janssen, 2, 5, MoonLake Pharma, 2, Novartis, 2, 5, Solara, 2, UCB, 2; J. Scher: Bristol-Myers Squibb(BMS), 2, Johnson & Johnson, 2, 5, Novartis, 2, Pfizer, 2, 5, UCB, 2; J. Gudjonsson: None; W. Liao: None; A. Ogdie: AbbVie, 5, Amgen, 5, 11, Bristol Myers Squibb, 5, Celgene, 5, CorEvitas, 2, Eli Lilly, 5, Novartis, 5, 11, Pfizer, 5, 11; C. Shiboski: None; A. Farris: Johnson & Johnson Innovative Medicine, 5; A. Baer: Bristol-Myers Squibb(BMS), 2; B. Warner: Mitobridge, subsidiary of Astellas Bio, 5, Pfizer, Inc., 5; J. Clemente: None; A. Heguy: None; M. Brenner: AbbVie/Abbott, 2, Johnson & Johnson, 5, Mestag Therapeutics, 2, 8, Moderna, 2, Ono Pharma, 5, Simcere, 2; N. Hacohen: Calico Biosciences, 5, Cytoreason, 1, 11, Danger Bio, 1, 11, Moderna, 5, Repertoire Immune Medicines, 1, 11, Takeda, 5; J. Guthridge: None; J. James: GlaxoSmithKlein(GSK), 2, Progentec, 5; S. Raychaudhuri: Bonito, 1, Bristol-Myers Squibb(BMS), 1, Janssen, 1, Mestag, 1, 8, Nimbus, 2, Pfizer, 1, Sonoma, 1, 8, Visterra, 6; L. Tsoi: Galderma, 5, Janssen, 5; X. Zhou: None; J. Welch: None; R. Clark: None; i. Korsunsky: Mestag therapeutics, 2; C. Lessard: Janssen Global Services, 2, Johnson & Johnson Innovative Medicine, 2, 5; K. Wei: 10X Genomics, 5, anaptysbio, 2, Gilead, 5, Merck/MSD, 5, Mestag, 2, Pfizer, 2.

To cite this abstract in AMA style:

Marlin C, Madhu R, Theisen E, Bradshaw L, Gao C, Eisenhaure T, Sugiarto N, Autoimmune and Immune Mediated Diseases A, Buyon J, Petri M, Rovin B, Werth V, Gravallese E, Anolik J, Moreland L, Donlin L, Ritchlin C, Scher J, Gudjonsson J, Liao W, Ogdie A, Shiboski C, Farris A, Baer A, Warner B, Clemente J, Heguy A, Brenner M, Hacohen N, Guthridge J, James J, Raychaudhuri S, Tsoi L, Zhou X, Welch J, Clark R, Korsunsky i, Lessard C, Wei K. Spatial Multi-omics Demonstrates Shared Immune States Across Autoimmune Diseases and Target Tissues in the Accelerating Medicines Partnership: Autoimmune and Immune-Mediated Diseases Network (AMP AIM) [abstract]. Arthritis Rheumatol. 2025; 77 (suppl 9). https://acrabstracts.org/abstract/spatial-multi-omics-demonstrates-shared-immune-states-across-autoimmune-diseases-and-target-tissues-in-the-accelerating-medicines-partnership-autoimmune-and-immune-mediated-diseases-network-amp-aim/. Accessed .

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