ACR Meeting Abstracts

ACR Meeting Abstracts

Abstract Number: 1940

A Circulating Reservoir of Pathogenic-like CD4+ T Cells Shares a Genetic and Phenotypic Signature with the Inflamed Synovial Micro-Environment

Roberto Spreafico1,2, Maura Rossetti1,2, Jorg van Loosdregt1, Carol A. Wallace3, Margherita Massa4, Silvia Magni-Manzoni5, Marco Gattorno6, Alberto Martini7, Daniel Lovell8,9 and Salvatore Albani2,10, 1Sanford-Burnham Medical Research Institute, La Jolla, CA, 2SingHealth Translational Immunology and Inflammation Centre, Singapore Health Services Pte Ltd, Singapore, Singapore, 3Seattle Children’s Hospital and Research Institute, Seattle, WA, 4Lab Biotecnologie, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy, 5Pediatric Rheumatology, IRCCS Ospedale Pediatrico Bambino Gesù, Rome, Italy, 6Instituto Giannina Gaslini and University of Genova, Genova, Italy, 7Istituto G. Gaslini, Universita' di Genova, Genova, Italy, 8Cincinnati Children's Hospital Medical Center, Cincinnati, OH, 9Rheumatology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, 10Duke-National University of Singapore Graduate Medical School, Singapore, Singapore

Meeting: 2015 ACR/ARHP Annual Meeting

Date of first publication: September 29, 2015

Keywords: , ,

Session Information

Date: Monday, November 9, 2015

Title: T cell Biology and Targets in Autoimmune Disease Poster I

Session Type: ACR Poster Session B

Session Time: 9:00AM-11:00AM

Background/Purpose: Systemic immunological processes are profoundly shaped by the micro-environments where antigen recognition occurs. Identifying molecular signatures distinctive of such processes is pivotal to understand pathogenic immune responses and manipulate them for therapeutic purposes. Unfortunately, direct investigation of peripheral tissues, enriched in pathogenic T cells, is often impossible or imposingly invasive in humans. Conversely, blood is easily accessible, but pathogenic signatures are diluted systemically as a result of the strict compartmentalisation of immune responses. In this work, we aimed at defining immune mediators shared between the bloodstream and the synovial micro-environment, and relevant for disease activity in autoimmune arthritis.

Methods: CD4+ T cells from blood and synovium of patients with juvenile idiopathic arthritis (JIA) were immunophenotyped by flow cytometry. The TCR repertoire of a circulating subset showing similarity with the synovium was analysed through next-generation sequencing to confirm enrichment in synovial clonotypes. Finally, clinical relevance was established by monitoring this subset in the blood of patients with JIA and rheumatoid arthritis (RA).

Results: A small subset of circulating CD4+ T cells replicated the phenotypic signature of lymphocytes infiltrating the inflamed synovium. These circulating pathogenic-like lymphocytes (CPLs) were enriched in synovial clonotypes and exhibited strong production of pro-inflammatory cytokines. Importantly, CPLs were expanded in JIA patients not responding to therapy, and also correlated with disease activity in patients with RA.

Conclusion: CPLs provide an accessible reservoir of pathogenic cells recirculating into the bloodstream and correlating with disease activity, to be exploited for diagnostic and research purposes.

Disclosure: R. Spreafico, None; M. Rossetti, None; J. van Loosdregt, None; C. A. Wallace, None; M. Massa, None; S. Magni-Manzoni, None; M. Gattorno, None; A. Martini, Abbott, Abbvie, Amgen, Biogenidecm Bristol MyersSquibb, Astellas, Behringer, Italfarmaco, Janssen, MedImmune, Novartis, NovoNordisk, Pfizer, Sanofi, Roche, Servier, Takeda., 8,Abbott, BMS, "Francesco Angelini", GlaxoSmithKline (GSK), Hoffman-La Roche, Italfarmaco, Janssen, Novartis, Pfizer, Sanofi Aventis, Schwarz Biosciences, Sobi, Xoma, Wyeth., 9; D. Lovell, National Institutes of Health, 2,Astra-Zeneca, Bristol Meyers Squibb, AbbVee, Pfizer, Roche, Novartis, UBC, Forest Research Institute, Horizon, Johnson & Johnson, Biogen, Takeda, Genentech, Glaxo Smith Kline, Boehringer Ingelheim, Celgene, Jannsen, 5,Genentech, Roche, Novartis, 8; S. Albani, None.

To cite this abstract in AMA style:

Spreafico R, Rossetti M, van Loosdregt J, Wallace CA, Massa M, Magni-Manzoni S, Gattorno M, Martini A, Lovell D, Albani S. A Circulating Reservoir of Pathogenic-like CD4+ T Cells Shares a Genetic and Phenotypic Signature with the Inflamed Synovial Micro-Environment [abstract]. Arthritis Rheumatol. 2015; 67 (suppl 10). https://acrabstracts.org/abstract/a-circulating-reservoir-of-pathogenic-like-cd4-t-cells-shares-a-genetic-and-phenotypic-signature-with-the-inflamed-synovial-micro-environment/. Accessed .

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