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: 1925

Interleukin-35 Is Upregulated in Systemic Sclerosis and Its Serum Levels Are Increased in Early Disease

Michal Tomcík1, Pawel Zerr2, Katrin Palumbo-Zerr2, Hana Storkanova1, Hana Hulejova3, Maja Spiritovic4, Ondrej Kodet5, Jiri Stork5, Radim Becvar1, Jiri Vencovsky1, Karel Pavelka6, Maria Filkova7, Jorg HW Distler2 and Ladislav Senolt8, 1Institute of Rheumatology, Department of Rheumatology, 1st Faculty of Medicine, Charles University, Prague, Czech Republic, 2Department of Internal Medicine 3 and Institute for Clinical Immunology, University of Erlangen-Nuremberg, Erlangen, Germany, 3Institute of Rheumatology and Department of Rheumatology, Prague, Czech Republic, 4Faculty of Physical Education and Sport, Charles University, Prague, Czech Republic, 5Department of Dermatology and Venereology, First Faculty of Medicine, Charles University, Prague, Czech Republic, 6Charles University, Prague, Czech Republic, 7Institute of Rheumatology and Department of Rheumatology, 1st Faculty of Medicine, Charles University, Prague, Czech Republic, 8Institute of Rheumatology and Department of Rheumatology, 1st Faculty of Medicine, Charles University, Prague, Czech Republic, Prague, Czech Republic

Meeting: 2015 ACR/ARHP Annual Meeting

Date of first publication: September 29, 2015

Keywords: Capillaroscopy, Fibroblasts, fibrosis, interleukins (IL) and systemic sclerosis

  • Tweet
  • Email
  • Print
Save to PDF
Session Information

Date: Monday, November 9, 2015

Session Title: Systemic Sclerosis, Fibrosing Syndromes and Raynaud's - Pathogenesis, Animal Models and Genetics Poster I

Session Type: ACR Poster Session B

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

Background/Purpose: Interleukin-35 (IL-35) is the most recent addition to the IL-12 family, which also comprises IL-12, IL-23 and IL-27. IL-35 consists of two chains, p35/IL-12a and EBI3/IL-27b, and exerts immunomodulatory activities in experimental and human autoimmune inflammatory conditions. Its potential role has been proposed in the pathogenesis of rheumatoid arthritis, sarcoidosis and systemic lupus erythematosus. However, its role in systemic sclerosis (SSc) has not been studied to date. The aim of this study was to assess IL-35 expression in the skin, dermal fibroblasts and circulation of SSc patients and characterize its potential association with SSc-related features.

Methods: Expression of IL-35 in the skin and dermal fibroblasts was quantified by qPCR, immunohistochemistry and immunofluorescence. Serum levels of IL-35 were analyzed by high sensitivity ELISA (Life Sciences, Hubei, PRC), and routine laboratory parameters such as CRP (by turbidimetry), ANA (by immunofluorescence) and autoantibodies of the ENA complex (by immunoblot) were measured in 40 SSc patients who met the EULAR/ACR 2013 criteria for SSc. Serum IL-35 was also determined in 40 healthy volunteers matched by age and sex.

Results: IL-35 chains EBI3 and p35 were overexpressed in the fibrotic skin of patients with SSc compared to that of healthy controls on both mRNA (p<0.05, p<0.05) and protein level (p<0.001, p<0.001). In fibrotic SSc skin, in contrast to non-fibrotic healthy skin, prominent staining for both IL-35 subunits was detected in dermal fibroblasts, myofibroblasts and perivascular inflammatory cells. Overexpression of IL-35 persisted in cultured dermal fibroblasts from SSc patients which maintained an increased mRNA (p<0.05, p<0.05) and protein level of both IL-35 subunits and released increased levels of IL-35 into supernatants (p<0.05) compared to healthy dermal fibroblasts. Stimulation with the main pro-fibrotic cytokine, TGF-β, increased the mRNA (p<0.05, p<0.05) and protein levels of both IL-35 chains, and enhanced the release of IL-35 into the supernatants (p<0.05), as well. Incubation with recombinant IL-35 induced an activated phenotype in resting fibroblasts (increased the expression of α-smooth muscle actin and stress fibers) and enhanced the release of collagen in a dose-dependent manner. IL-35 serum levels were increased in patients with SSc compared to healthy controls (median(IQR): 83.9 (45.1–146.1) vs. 36.2 (17.2–49.4) pg/ml, p<0.0001). Furthermore, serum IL-35 negatively correlated with disease duration (p<0.01, r=-0.434), and was increased in patients with early SSc pattern on capillaroscopy assessment compared to those with active and late SSc patterns (p<0.05, p<0.05). No correlations of serum IL-35 with other SSc-related features were observed.

Conclusion:

The present study demonstrates an overexpression of IL-35 in the skin, dermal fibroblasts and serum of SSc patients. TGF-β induces IL-35, which in turn activates resting fibroblasts and enhances the release of collagen thereby contributing to aberrant TGF-β signaling in SSc. Elevated serum IL-35 is associated with early, inflammatory stages of SSc.

Acknowledgement: Supported by IGA12440-4, MHCR023728.


Disclosure: M. Tomcík, None; P. Zerr, None; K. Palumbo-Zerr, None; H. Storkanova, None; H. Hulejova, None; M. Spiritovic, None; O. Kodet, None; J. Stork, None; R. Becvar, Actelion Pharmaceuticals US, 5; J. Vencovsky, None; K. Pavelka, None; M. Filkova, None; J. H. Distler, None; L. Senolt, None.

To cite this abstract in AMA style:

Tomcík M, Zerr P, Palumbo-Zerr K, Storkanova H, Hulejova H, Spiritovic M, Kodet O, Stork J, Becvar R, Vencovsky J, Pavelka K, Filkova M, Distler JH, Senolt L. Interleukin-35 Is Upregulated in Systemic Sclerosis and Its Serum Levels Are Increased in Early Disease [abstract]. Arthritis Rheumatol. 2015; 67 (suppl 10). https://acrabstracts.org/abstract/interleukin-35-is-upregulated-in-systemic-sclerosis-and-its-serum-levels-are-increased-in-early-disease/. Accessed March 3, 2021.
  • Tweet
  • Email
  • Print
Save to PDF

« Back to 2015 ACR/ARHP Annual Meeting

ACR Meeting Abstracts - https://acrabstracts.org/abstract/interleukin-35-is-upregulated-in-systemic-sclerosis-and-its-serum-levels-are-increased-in-early-disease/

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.