DoCTIS: A Single Cell RNA-Seq Atlas of Drug Response To Targeted Therapies

Antonio Julià¹, Yolanda Guillén², Paloma Vela Casasempere³, Antonio Fernández Nebro⁴, Carlos Marras⁵, Santos Castañeda⁶, Jaime Calvo Alén⁷, Jesús Tornero Molina⁸, Juan Cañete⁹, Eugeni Domènech¹⁰, Javier Gisbert¹¹, Jose M. Carrascosa¹², Eduardo Fonseca¹³, Luis Bujanda Fernández De pierola¹⁴, Valle García Sánchez¹⁵, Britta Siegmund¹⁶, Giampiero Girolomoni¹⁷, Holger Heyn¹⁸, Laura Jiménez Gracia¹⁸, Pere Santamaria¹⁹, Edgar Angelats²⁰, Richard Myers²¹, Sergio H. Martínez Mateu², Juan Ángel Patiño Galindo², Ernest Choy²² and Sara Marsal¹, ¹Vall d'Hebron Hospital Research Institute, Rheumatology Research Group, Barcelona, Spain, ²IMIDomics, Barcelona, Spain, ³Hospital General Universitario de Alicante, Rheumatology, Alicante, Spain, ⁴Hospital Regional Universitario Carlos Haya, Rheumatology, Málaga, Spain, ⁵Hospital Universitario Virgen de la Arrixaca, Rheumatology, Murcia, Spain, ⁶Hospital Universitario de La Princesa, IIS-Princesa, Madrid, Madrid, Spain, ⁷Hospital Universitario de Araba, Rheumatology, Vitoria, Spain, ⁸Hospital Universitario de Guadalajara, Rheumatology, Guadalajara, Spain, ⁹Rheumatology Department, Hospital Clínic and IDIBAPS, Barcelona, Spain, Barcelona, Spain, ¹⁰Hospital Universitari Germans Trias i Pujol, Gastroenterology, Badalona, Spain, ¹¹Hospital Universitario La Princesa, Rheumatology, Madrid, Spain, ¹²Hospital Universitari Germans Trias i Pujol, Dermatology, Badalona, Spain, ¹³Complejo Hospitalario Universitario de A Coruña, Dermatology, A Coruña, Spain, ¹⁴Hospital Universitario de Donostia, Gastroenterology, San Sebastián, Spain, ¹⁵Hospital Universitario Reina Sofía, Gastroenterology, Córdoba, Spain, ¹⁶Charité-Universitätsmedizin Berlin, Gastroenterology, Berlin, Germany, ¹⁷University of Verona, Dermatology, Verona, Spain, ¹⁸Centre for Genomic Regulation (CNAG-CRG), Barcelona, Spain, ¹⁹Institut d'Investigacions Biomèdiques August Pi i Sunyer, Barcelonoa, Spain, ²⁰Hospital Clínic-IDIBAPS, Barcelona, Spain, ²¹HudsonAlpha Institute for Biotechnology, Huntsville, AL, ²²Division of Infection and Immunity, CREATE Centre, Cardiff University, Cardiff, United Kingdom

Meeting: ACR Convergence 2025

Keywords: Anti-TNF Drugs, autoimmune diseases, genomics, immunology

Session Information

Date: Sunday, October 26, 2025

Title: (0019–0048) Genetics, Genomics & Proteomics Poster

Session Type: Poster Session A

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

Background/Purpose: Targeted therapies have revolutionized the management of immune-mediated inflammatory diseases (IMIDs), however, there is a substantial number of patients who respond poorly to a given drug. There is a big need to understand the factors that are associated with this heterogeneity. The DoCTIS project aims to characterize molecular variation both at the disease and drug-response levels across six different IMIDs.

Methods: We applied single cell RNA sequencing to 360 samples from 176 patients from six prevalent IMIDs -psoriasis, psoriatic arthritis, Crohn’s Disease, ulcerative colitis, rheumatoid arthritis, systemic lupus erythematosus- treated with five different drugs targeting TNF, IL12p40, IL6R, BLySS, IL17 and JAK pathways. All patients were analyzed at two time points including baseline and at the week of clinical response creating an immune landscape of more than two million peripheral immune cells.

Results: We found large inter-disease differences both at the compositional and genetic regulatory programs. ScRNA-Seq analysis revealed large differences at the systemic level between the six IMIDs. We found expected findings, like the predominant interferon response signature affecting multiple cell types in SLE, but also novel findings like strong regulatory differences between diseases with a shared genetic risk like Psoriatic Arthritis and Psoriasis. The impact of each drug was found to be largely disease-specific. Furthermore, we found multiple regulatory features associated with the effect of each drug as well the association to response.

Conclusion: The scRNA-Seq atlas developed in DoCTIS provides a unique resource for the understanding of drug response and disease heterogeneity across immune-mediated inflammatory diseases.

Disclosures: A. Julià: None; Y. Guillén: None; P. Vela Casasempere: AbbVie/Abbott, 5, 6, AstraZeneca, 5, GlaxoSmithKlein(GSK), 2, 5, 6, Lilly, 5, 6, Novartis, 5, Pfizer, 5, Roche, 5; A. Fernández Nebro: None; C. Marras: None; S. Castañeda: None; J. Calvo Alén: None; J. Tornero Molina: None; J. Cañete: None; E. Domènech: AbbVie/Abbott, 1, 5, 6, Adacyte Therapeutics, 1, 5, 6, Biogen, 1, 5, 6, Celltrion, 1, 5, 6, Ferring, 1, 5, 6, Galapagos, 1, 5, 6, Gilead, 1, 5, 6, GoodGut, 1, 5, 6, Janssen, 1, 5, 6, Kern Pharma, 1, 5, 6, Lilly, 1, 5, 6, Merck/MSD, 1, 5, 6, Pfizer, 1, 5, 6, Roche, 1, 5, 6, Samsung, 1, 5, 6, Takeda, 1, 5, 6, Tillots, 1, 5, 6; J. Gisbert: None; J. Carrascosa: AbbVie/Abbott, 1, 2, 6, almirall, 2, 6, Amgen, 1, 6, Boehringer-Ingelheim, 1, 6, Bristol-Myers Squibb(BMS), 1, 6, Eli Lilly, 1, 6, galderma, 1, 6, imidomics, 1, johsson and johnsson, 1, 6, leo pharma, 1, Novartis, 1, 2, 6, Pfizer, 1, 6, sanofi, 1, 6, UCB, 1; E. Fonseca: None; L. Bujanda Fernández De pierola: None; V. García Sánchez: None; B. Siegmund: AbbVie/Abbott, 2, 6, Abivax, 2, AlfaSigma, 6, Boehringer-Ingelheim, 2, Bristol-Myers Squibb(BMS), 2, 6, CED Service GmbH, 6, Dr. Falk Pharma, 2, 6, Eli Lilly, 2, Endpoint Health, 2, Falk, 2, Ferring, 6, Galapagos, 2, 6, Gilead, 2, Janssen, 2, 6, Landos, 2, Lilly, 2, Materia Prima, 2, MSD, 6, Pfizer, 2, 5, 6, PredictImmune, 2, Takeda, 2, 6; G. Girolomoni: None; H. Heyn: Genentech, 6, Moderna, 2, Nanostring, 1, Omniscope, 4, 8, Singularity, 2; L. Jiménez Gracia: None; P. Santamaria: Parvus Therapeutics, 4, 8, Sanofi, 2; E. Angelats: None; R. Myers: None; S. Martínez Mateu: None; J. Patiño Galindo: None; E. Choy: AbbVie, 2, 6, Alfasigma, 6, Bio-Cancer, 2, 5, Biocon, 2, Biogen, 2, 5, Chugai Pharma, 2, 6, Eli Lilly, 6, Fresenius Kabi, 2, 6, Gedeon Richter, 2, 6, Gilead, 2, Janssen, 2, 6, Pfizer, 2, 5, 6, Sanofi, 2, 5, 6, UCB, 2, 6, Viatris, 2, 6; S. Marsal: AbbVie/Abbott, 5, Bristol-Myers Squibb(BMS), 5, Eli Lilly, 1, 5, IMIDomics, 4, 8, Janssen, 5, Merck/MSD, 5, Novartis, 5, Roche, 5, UCB, 5.

To cite this abstract in AMA style:

Julià A, Guillén Y, Vela Casasempere P, Fernández Nebro A, Marras C, Castañeda S, Calvo Alén J, Tornero Molina J, Cañete J, Domènech E, Gisbert J, Carrascosa J, Fonseca E, Bujanda Fernández De pierola L, García Sánchez V, Siegmund B, Girolomoni G, Heyn H, Jiménez Gracia L, Santamaria P, Angelats E, Myers R, Martínez Mateu S, Patiño Galindo J, Choy E, Marsal S. DoCTIS: A Single Cell RNA-Seq Atlas of Drug Response To Targeted Therapies [abstract]. Arthritis Rheumatol. 2025; 77 (suppl 9). https://acrabstracts.org/abstract/doctis-a-single-cell-rna-seq-atlas-of-drug-response-to-targeted-therapies/. Accessed .

« Back to ACR Convergence 2025

ACR Meeting Abstracts - https://acrabstracts.org/abstract/doctis-a-single-cell-rna-seq-atlas-of-drug-response-to-targeted-therapies/