Autoimmune rheumatologic diseases

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Perturbations Within the T Cell Immunome in Polyarticular Juvenile Idiopathic Arthritis Patients Who Relapse upon Withdrawal of Biologic Therapy

Thursday, June 15
5:45 PM - 7:00 PM

Clinical management of polyarticular JIA with anti-TNF-alpha biologics has been met with significant success, with up to 80% of patients demonstrating clinically meaningful efficacy. However, concerns about drug toxicities and costs have driven the clinical need to find predictors for successful drug discontinuation. Previous published data suggests a pivotal role for T cells in disease progression. To distill this pathogenic signal located within the T cell immunome, a high dimensional single cell resolution platform, CyToF, was deployed. Patients treated with anti-TNF-alpha who demonstrated at least 6 months of clinical inactive disease on medication (Wallace criteria) were enrolled in the Understanding TNF-alpha trial and segregated into flare or no flare arms (evaluated based on 6 JIA core set parameters) after discontinuation of therapy. PBMCs from n=39 JIA patients (19 flare, 20 no flare) and n=20 healthy paediatric controls were stained with a 37 markers T cell CyToF panel. Cluster analysis reveal a dysregulated CD4 T cell memory compartment (CD69+CD28+ICOS+TNF-alphahi) prior to therapy withdrawal that is predictive for flare (p< 0.05). Upon flare, this population of TNF-alpha+ memory cells have expanded into a) IL-6+, b) IFN-g+, c) CD152+ or purely retaining TNF-alpha expression (p< 0.05). Concomitantly this dysregulation extends into the CD8 memory compartment (CD8 IFN-g+TNF-alpha+ , p < 0.05). These results suggest that clinical fate is immunologically predetermined and patients who will realize different clinical fates can be identified from prior biologic sampling.

Jing Yao Leong

Research fellow
SingHealth Translational Immunology and Inflammation Centre

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    Joo Guan Yeo

    SingHealth Translational Immunology and Inflammation Centre

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      Phyllis Chen

      SingHealth Translational Immunology and Inflammation Centre, Singapore Health Services Pte Ltd

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        Lai Liyun

        SingHealth Translational Immunology and Inflammation Centre, Singapore Health Services Pte Ltd

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          Loshinidevi D/O Thana Bathi

          SingHealth Translational Immunology and Inflammation Centre, Singapore Health Services Pte Ltd

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            Justin Tan

            Consultant, Rheumatology and Immunology Service
            KK Women’s and Children’s Hospital

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              Thaschawee Arkachaisri

              Senior Consultant and Head of Rheumatology and Immunology Service
              KK Women’s and Children’s Hospital and Duke-NUS Graduate Medical School Singapore

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                Daniel J. Lovell

                Associate Director, Division of Rheumatology
                Division of Rheumatology, Cincinnati Children's Hospital Medical Center and Department of Paediatrics, University of Cincinnati College of Medicine.

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                  Salvatore Albani

                  Director
                  SingHealth Translational Immunology and Inflammation Centre, Duke-NUS Graduate Medical School, Singapore

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