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: 2023

Different Patterns of Interferon-Response-Gene Expression May Elucidate Different Pathomechanisms That Drive IFN-Response-Gene Activation in Patients with Presumed IFN-Mediated Autoinflammatory Diseases

Adriana Almeida de Jesus1, Yanfeng Hou2, Louise Malle3, Scott Canna4, Gina A. Montealegre Sanchez1, Hanna Kim5, Rachel VanTries1, Seza Ozen6, Samantha Dill7, Dawn C. Chapelle7, Bernadette Marrero1, Yan Huang1, Angelique Biancotto8 and Raphaela Goldbach-Mansky1, 1Translational Autoinflammatory Disease Section (TADS), Laboratory of Clinical Investigation and Microbiology (LCIM), NIAID/NIH, Bethesda, MD, 2Department of Rheumatology, Shandong Provincial Qianfoshan Hospital, Shandong University, Shandong, China, 3Icahn School of Medicine at Mount Sinai, New York, NY, 4RK Mellon Institute for Pediatric Research, University of Pittsburgh/Children's Hospital of Pittsburgh of UPMC, Pittsburrgh, PA, 5Pediatric Translational Research Branch, NIAMS, NIH, Bethesda, MD, 6Hacettepe University Vasculitis Center (HUVAC), Ankara, Turkey, 7Pediatric Translational Research Branch, NIAMS/NIH, Bethesda, MD, 8Center for Human Immunology Autoimmunity and Inflammation (CHI), NIAID, NIH, Bethesda, MD

Meeting: 2018 ACR/ARHP Annual Meeting

Keywords: Autoinflammatory Disease, Biomarkers, cytokines and interferons, Gene Expression

  • 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: Tuesday, October 23, 2018

Title: Pediatric Rheumatology – Basic Science Poster

Session Type: ACR Poster Session C

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

Background/Purpose: Many infants and children with early-onset autoinflammatory diseases are mutation-negative for genetically known autoinflammatory diseases. Recent data suggest a role for Type-I interferon dysregulation in causing autoinflammatory disease phenotypes with clinical features that are distinct from those found in patients with IL-1 mediated autoinflammatory diseases. We assessed an IFN–response-gene signature (IRS), characterized the clinical phenotypes, IFN-related biomarkers and genetic causes.

Methods: We assessed IFN-response gene signatures (IRS) from 63 consecutively evaluated patients who were negative for known autoinflammatory disease-causing mutations. Whole blood gene expression of 28 selected interferon response genes (IRG) was determined by Nanostring and an IFN-score was calculated. Serum levels of 48 cytokines were measured by a multiplex immunoassay.Patients underwent clinical assessments and genetic analyses were performed by whole exome/genome sequencing (WES/WGS).

Results: Of 63 patients tested, 36 had elevated IFN-signatures. Patients with high IRS had higher frequencies of panniculitis (58 vs 0%, p<0.0001), basal ganglia calcifications (45 vs 0%, p=0.0043), interstitial lung disease (ILD) (48 vs 4.8%, p=0.0013), myositis (65 vs 15%, p=0.0005), skin vasculitis (29 vs 7.4%, p=0.05), arterial hypertension (32 vs 3.7%, p=0.011) and liver disease (73 vs 22%, p=0.0002), than patients without an IRS. Of 8 distinct clinical patterns, one group with pulmonary alveolar proteinosis (PAP) and macrophage activation syndrome (MAS) had high IL-18 serum levels. Other groups included 2 patients with novel LRBA mutations, 3 patients with a novel NEMO splice site mutation, 5 with de novo truncating SAMD9L mutations, 2 with myositis and anti-MDA5 autoantibodies, 7 with CANDLE-like panniculitis of which 1 had a known PSMB8 mutations and 2 had novel proteasome mutations in PSMB8 and in PSMG2, respectively. Patients with PAP and MAS, LRBA, NEMO, SAMD9L mutations had overall lower IFN scores and significantly lower USP18 but higher SOCS1 transcript levels compared to CANDLE and SAVI, both negative regulators of IFN signaling. SOCS1 transcription is regulated through the NF-κB signaling pathway and SOCS1 expression dysregulation may point to a different origin of the IFN response gene signature compared to CANDLE and SAVI patients. Interestingly, many of these patients with high SOCS1 and lower USP18 levels responded to TNF inhibition. Additionally, patients with high IRS had significantly higher serum levels of IP-10, MIG, MIP1α, MIP1β, SCF and GROα than those with negative IFN scores.

Conclusion: The assessment of patients with IFN signatures revealed distinct clinical pathogenically defined disease subsets. In 3 subgroups of patients, novel monogenic disease-causing mutations were detected. The contribution of SOCS1 and USP18 may assist in delineating different intracellular pathways that lead to the activation of the IFN response gene signature.

Acknowledgements: This work was supported by the NIH IRP of NIAID. We would like to thank the autoinflammatory disease network of physicians for patient referral.


Disclosure: A. Almeida de Jesus, None; Y. Hou, None; L. Malle, None; S. Canna, AB2 Bio, Ltd, 5; G. A. Montealegre Sanchez, None; H. Kim, None; R. VanTries, None; S. Ozen, None; S. Dill, None; D. C. Chapelle, None; B. Marrero, None; Y. Huang, None; A. Biancotto, None; R. Goldbach-Mansky, None.

To cite this abstract in AMA style:

Almeida de Jesus A, Hou Y, Malle L, Canna S, Montealegre Sanchez GA, Kim H, VanTries R, Ozen S, Dill S, Chapelle DC, Marrero B, Huang Y, Biancotto A, Goldbach-Mansky R. Different Patterns of Interferon-Response-Gene Expression May Elucidate Different Pathomechanisms That Drive IFN-Response-Gene Activation in Patients with Presumed IFN-Mediated Autoinflammatory Diseases [abstract]. Arthritis Rheumatol. 2018; 70 (suppl 9). https://acrabstracts.org/abstract/different-patterns-of-interferon-response-gene-expression-may-elucidate-different-pathomechanisms-that-drive-ifn-response-gene-activation-in-patients-with-presumed-ifn-mediated-autoinflammatory-diseas/. 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 2018 ACR/ARHP Annual Meeting

ACR Meeting Abstracts - https://acrabstracts.org/abstract/different-patterns-of-interferon-response-gene-expression-may-elucidate-different-pathomechanisms-that-drive-ifn-response-gene-activation-in-patients-with-presumed-ifn-mediated-autoinflammatory-diseas/

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