ACR Meeting Abstracts

ACR Meeting Abstracts

  • Home
  • Meetings Archive
    • ACR Convergence 2020
    • 2020 ACR/ARP PRSYM
    • 2019 ACR/ARP Annual Meeting
    • 2018 ACR/ARHP Annual Meeting
    • 2017 ACR/ARHP Annual Meeting
    • 2017 ACR/ARHP PRSYM
    • 2016-2009 Meetings
    • Download Abstracts
  • Keyword Index
  • Advanced Search
  • Your Favorites
    • Favorites
    • Login
    • Register
    • View and print all favorites
    • Clear all your favorites
  • Meeting Resource Center

Abstract Number: 953

Persistence of Pathogenic CD4 Memory T Cells Revealed through Cytometry Time of Flight in Juvenile Idiopathic Arthritic Patients with Disease Resurgence upon Withdrawal of Anti-TNFA Biologics

Jing Yao Leong1, Joo Guan Yeo2, Phyllis Chen3, Liyun Lai4, Fauziah Ally5, Loshinidevi D/O Thana Bathi3, Justin Hung Tiong Tan2, Thaschawee Arkachaisri2, Femke van Wijk6, Salvatore Albani4, Daniel J Lovell7 and Gerdien Mijnheer8, 1SingHealth Translational Immunology and Inflammation Centre, Singapore Health Services Pte Ltd, Singapore, Singapore, 2Rheumatology and Immunology Service, KK Women's and Children's Hospital, Singapore, Singapore, 3Singhealth Translational Immunology and Inflammation Centre (STIIC), Duke-NUS Medical School, Singapore, Singapore, 4SingHealth Translational Immunology and Inflammation Centre (STIIC), Duke-NUS Medical School, Singapore, Singapore, 5STIIC, SingHealth Translational Immunology and Inflammation Centre, Singapore, Singapore, 6University Medical Center Utrecht, Utrecht, Netherlands, 7Rheumatology, PRCSG - Cincinnati Children's Hospital Medical Center, Cinncinnati, OH, 81Laboratory of Translational Immunology, Department of Paediatric Immunology, , The Netherlands, University Medical Centre Utrecht, Wilhelmina Children’s Hospital, Utrecht, Netherlands

Meeting: 2017 ACR/ARHP Annual Meeting

Date of first publication: September 18, 2017

Keywords: Biologics, CyTOF, juvenile idiopathic arthritis (JIA) and pathogenesis, T cells

  • Tweet
  • Email
  • Print
Save to PDF
Session Information

Date: Sunday, November 5, 2017

Session Title: T Cell Biology and Targets in Autoimmune Disease

Session Type: ACR Concurrent Abstract Session

Session Time: 4:30PM-6:00PM

Background/Purpose: Treatment of polyarticular JIA with anti-TNFA biologics has experienced significant success, with up to 80% of patients demonstrating clinically meaningful efficacy. Yet concerns regarding medium/long term toxicities and costs, have driven the clinical need to locate predictors for successful drug discontinuation. Compelling evidence indicate that T cells play a paramount role in disease progression. Identification of these pathogenic subsets within the T cell immunome will likely help stratify patients in terms of clinical fate. JIA patients previously treated with anti-TNFA were recruited through the Understanding TNFA trial and segregated into flare, active and inactive arms after drug discontinuation. Utilising a high dimensional platform, CyToF, that is capable of phenotyping up to 41 markers at single cell resolution, we aim to identify the pathogenic subsets responsible for clinical relapse and signatures capable of distinguishing therapeutic outcomes.

Methods: Patients treated with anti-TNF-alpha were recruited into the study (Improved Understanding of the Biology and Use of TNF inhibition in Children with JIA Trial) with clinically inactive disease on treatment (Wallace criteria) and initiated with therapy discontinuation. The patients were followed and evaluated as flare, inactive and active based on 6 JIA core set parameters; number of joints with active arthritis and/or loss of motion, MD global assessment of current disease activity, patient/parent global assessment of overall disease severity in prior week, a validated measure of physical function and ESR.

Results: PBMCs from 47 JIA patients (Flare= 18, Active= 11, Inactive= 18) and 10 healthy controls were stained and interrogated with CyToF. Patients destined to flare (vs inactive/healthy) prior to therapy withdrawal, displayed significant dysregulation in the CD4 Memory compartment (p< 0.05), enriched particularly in (a) CD4 CD45RA– TNFA+ , (b) CD4 CD45RA– CXCR5+, and were skewed towards (c) CD152– / PD1–. When contrasting against healthy controls, patients destined to flare additionally upregulated CD4 CD45RA– TNFA+ IL-6+, possibly a sub-clinical disease subset. Intriguingly we noted a migratory subset, CD4 CD45RA– CXCR3+ CCR6+ that was present in patients destined to develop active disease (vs inactive/healthy). Upon flaring, the sub-clinical subset CD4 CD45RA– TNFA+ IL-6+ surfaces and CD4 memory subsets are now upregulating expression of CD152/PD1 (vs inactive) in response to ongoing inflammation, but when compared to healthy controls are still inadequate. Parallel pathogenic subsets were also detected in the synovial microenvironment, reflecting targeting towards the joints.

Conclusion: For some patients (Flare), anti-TNFA therapy is merely suppressing disease activity and not curative. The persistence of CD4 memory cells are likely to play a pivotal role in disease relapse, that may be partially explained by a weaker control through immune checkpoints (CD152/PD1). These results suggest that clinical fate is immunologically predetermined and patients who will develop different clinical fates can be identified from prior biologic sampling.


Disclosure: J. Y. Leong, None; J. G. Yeo, None; P. Chen, None; L. Lai, None; F. Ally, None; L. D. T. Bathi, None; J. H. T. Tan, None; T. Arkachaisri, None; F. van Wijk, None; S. Albani, None; D. J. Lovell, None; G. Mijnheer, None.

To cite this abstract in AMA style:

Leong JY, Yeo JG, Chen P, Lai L, Ally F, Bathi LDT, Tan JHT, Arkachaisri T, van Wijk F, Albani S, Lovell DJ, Mijnheer G. Persistence of Pathogenic CD4 Memory T Cells Revealed through Cytometry Time of Flight in Juvenile Idiopathic Arthritic Patients with Disease Resurgence upon Withdrawal of Anti-TNFA Biologics [abstract]. Arthritis Rheumatol. 2017; 69 (suppl 10). https://acrabstracts.org/abstract/persistence-of-pathogenic-cd4-memory-t-cells-revealed-through-cytometry-time-of-flight-in-juvenile-idiopathic-arthritic-patients-with-disease-resurgence-upon-withdrawal-of-anti-tnfa-biologics/. Accessed January 25, 2021.
  • Tweet
  • Email
  • Print
Save to PDF

« Back to 2017 ACR/ARHP Annual Meeting

ACR Meeting Abstracts - https://acrabstracts.org/abstract/persistence-of-pathogenic-cd4-memory-t-cells-revealed-through-cytometry-time-of-flight-in-juvenile-idiopathic-arthritic-patients-with-disease-resurgence-upon-withdrawal-of-anti-tnfa-biologics/

Advanced Search

Your Favorites

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

ACR Convergence: Where Rheumatology Meets. All Virtual. November 5-9.

ACR Pediatric Rheumatology Symposium 2020

© COPYRIGHT 2021 AMERICAN COLLEGE OF RHEUMATOLOGY

Wiley

  • Home
  • Meetings Archive
  • Advanced Search
  • Meeting Resource Center
  • Online Journal
  • Privacy Policy
  • Permissions Policies
loading Cancel
Post was not sent - check your email addresses!
Email check failed, please try again
Sorry, your blog cannot share posts by email.
This site uses cookies: Find out more.