ACR Meeting Abstracts

ACR Meeting Abstracts

  • Meetings
    • ACR Convergence 2024
    • ACR Convergence 2023
    • 2023 ACR/ARP PRSYM
    • ACR Convergence 2022
    • ACR Convergence 2021
    • ACR Convergence 2020
    • 2020 ACR/ARP PRSYM
    • 2019 ACR/ARP Annual Meeting
    • 2018-2009 Meetings
    • Download Abstracts
  • Keyword Index
  • Advanced Search
  • Your Favorites
    • Favorites
    • Login
    • View and print all favorites
    • Clear all your favorites
  • ACR Meetings

Abstract Number: 1254

Deciphering the Immunome of Clinically Effective Immune Tolerization in Rheumatoid Arthritis

Jing Yao Leong1,2, Raymond Ong Jr.3, Juntao Li4, Theodorus van den Broek5, Roberto Spreafico4, Maura Rossetti1 and Salvatore Albani1,2, 1SingHealth Translational Immunology and Inflammation Centre, Singapore Health Services Pte Ltd, Singapore, Singapore, 2Duke-National University of Singapore Graduate Medical School, Singapore, Singapore, 3Singhealth Translational Immunology and Inflammation Centre (STIIC), Singapore Health Services Pte Ltd, Singapore, Singapore, 4SingHealth Translational Immunology and Inflammation Centre (STIIC), Singapore Health Services Pte Ltd, Singapore, Singapore, 5Translational Research Unit, Sanford-Burnham Medical Research Institute, La Jolla, CA

Meeting: 2015 ACR/ARHP Annual Meeting

Date of first publication: September 29, 2015

Keywords: Bioinformatics, Clinical research, rheumatoid arthritis, treatment and tolerance

  • Tweet
  • Click to email a link to a friend (Opens in new window) Email
  • Click to print (Opens in new window) Print
Session Information

Date: Monday, November 9, 2015

Title: Genetics, Genomics and Proteomics Poster II

Session Type: ACR Poster Session B

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

Background/Purpose:

We have previously described (Nature Medicine, PNAS, A&R, Nature
Rheum, Lancet
)
how oral treatment with the pro-inflammatory, heat shock protein-derived dnaJP1
peptide induces detectable clinical amelioration in Phase I and IIa clinical
studies in rheumatoid arthritis. In previous work, we have also identified T
effector (Teff) immune deviation and an increase in
PD-1 Treg subsets as some of the immune mechanisms leading to clinical
improvement. Clinical and immunological data also emphasized a synergistic
effect with hydroxychloroquine (HCQ). Our previous studies, however, did not capture, yet, the co
mplexity of the dynamic interactions among subsets of 
immune cells. Here, we apply a novel approach aiming at addressing this unmet
need.   

      

Methods:

Patient selection, randomization treatment and assessment
of clinical outcomes were prev
iously described (Koffeman, et al 2009, Arthritis &
Rheumatism). Antibody panels were d
esigned, based on previous specific experience and data, to encompass the
major subsets of immune cells and employed to study by flow cytometry PBMCs
from two treatment cohorts: (a) dnaJP1-HCQ r
esponders (n=6) (b) Placebo HCQ Non
Responders (n=
10)
We have su
bstantially modified and adapted for use
in translational research the clustering software ACCENSE (Shekhar, et al,
2014, PNAS). The work flow is presented in Fig. 1,
and FD is defined as fold difference percentage of responders over non
responders cells.   

Results:

T cell subsets which were significantly more represented in
dnaJP1 responders were antigen experienced, activated T cells which displayed tolerogenic/regulatory characteristics (CD4
+CD45RO+TGF-BintCD69int , FD= 17) and (CD4+HLA-DRhiGITRint/high, FD = 27).  Intriguingly we also detected FoxP3hi T cells which may represent regulatory
subsets transiting between inflammatory (CCR5
hiCXCR3hi, FD = 9) and
mucosal (CD103
hiCD27hiCD62Lhi, FD = 7) compartments.

Analysis of the antigen presentation cells (APCs)
compartment revealed two functionally di
stinct subsets which are significantly elevated in dnaJP1 clinical
responders, both subsets probably the outcome of
cross talk between tolerized/regulatory T cells and APC: (a) CD14
+CD16+CD303hiCD141hi (FD = 10) monocytes that exhibit CD86hi expression, which has been described to
relate to and augment Treg function, (b) APCs which manifest a mature phenotype (CD83
+), subdivided into 3 lineages (i) CD19hi B cells (FD = 9), (ii) dendritic cells CD1chi (FD = 72) and (iii) CD1clo (FD = 19).

Analysis work flow.jpg

Conclusion:

A holistic approach to the immunome confirmed the
specificity and complexity of the i
mmune tolerization mechanism, which relies on
the interplay between effector and regulatory T cells and APC. This approach
has a dual translational value, as it provides mechanistic knowledge and also
potential biomarkers directly related to the therapeutic intervention.


Disclosure: J. Y. Leong, None; R. Ong Jr., None; J. Li, None; T. V. D. Broek, None; R. Spreafico, None; M. Rossetti, None; S. Albani, Patent, 9.

To cite this abstract in AMA style:

Leong JY, Ong R Jr., Li J, Broek TVD, Spreafico R, Rossetti M, Albani S. Deciphering the Immunome of Clinically Effective Immune Tolerization in Rheumatoid Arthritis [abstract]. Arthritis Rheumatol. 2015; 67 (suppl 10). https://acrabstracts.org/abstract/deciphering-the-immunome-of-clinically-effective-immune-tolerization-in-rheumatoid-arthritis/. Accessed .
  • Tweet
  • Click to email a link to a friend (Opens in new window) Email
  • Click to print (Opens in new window) Print

« Back to 2015 ACR/ARHP Annual Meeting

ACR Meeting Abstracts - https://acrabstracts.org/abstract/deciphering-the-immunome-of-clinically-effective-immune-tolerization-in-rheumatoid-arthritis/

Advanced Search

Your Favorites

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

All abstracts accepted to ACR Convergence are under media embargo once the ACR has notified presenters of their abstract’s acceptance. They may be presented at other meetings or published as manuscripts after this time but should not be discussed in non-scholarly venues or outlets. The following embargo policies are strictly enforced by the ACR.

Accepted abstracts are made available to the public online in advance of the meeting and are published in a special online supplement of our scientific journal, Arthritis & Rheumatology. Information contained in those abstracts may not be released until the abstracts appear online. In an exception to the media embargo, academic institutions, private organizations, and companies with products whose value may be influenced by information contained in an abstract may issue a press release to coincide with the availability of an ACR abstract on the ACR website. However, the ACR continues to require that information that goes beyond that contained in the abstract (e.g., discussion of the abstract done as part of editorial news coverage) is under media embargo until 10:00 AM ET on November 14, 2024. Journalists with access to embargoed information cannot release articles or editorial news coverage before this time. Editorial news coverage is considered original articles/videos developed by employed journalists to report facts, commentary, and subject matter expert quotes in a narrative form using a variety of sources (e.g., research, announcements, press releases, events, etc.).

Violation of this policy may result in the abstract being withdrawn from the meeting and other measures deemed appropriate. Authors are responsible for notifying colleagues, institutions, communications firms, and all other stakeholders related to the development or promotion of the abstract about this policy. If you have questions about the ACR abstract embargo policy, please contact ACR abstracts staff at [email protected].

Wiley

  • Online Journal
  • Privacy Policy
  • Permissions Policies
  • Cookie Preferences

© Copyright 2025 American College of Rheumatology