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: 0930

The Common Form of the Inflammatory Skin Disease Hidradenitis Suppurativa Is Associated with Low Nicastrin Expression in Dermal Fibroblasts

Kaitlin Williams, Beita Badiei, Hana Minsky and Luis Garza, Johns Hopkins University School of Medicine, Baltimore, MD

Meeting: ACR Convergence 2024

Keywords: Dermatology, Fibroblasts, Dermal, Inflammation, skin

  • 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: Sunday, November 17, 2024

Title: Innate Immunity Poster

Session Type: Poster Session B

Session Time: 10:30AM-12:30PM

Background/Purpose: Hidradenitis suppurativa (HS) is a chronic inflammatory skin condition characterized by painful nodules and abscesses in intertriginous areas. Despite its increasing prevalence, the etiology of HS remains unclear. A minority of HS cases are familial, involving germline mutations in one of the subunits of the membrane protease complex gamma-secretase (GS). Mutations are most frequent in the nicastrin (NCSTN) subunit. NCSTN regulates access to the proteolytic site of GS, thereby regulating cleavage of its many substrates including Amyloid Precursor Protein (APP). Given the biologic importance of GS and its known association to familial HS, we hypothesized that NCSTN levels may be low in common non-familial HS and lead to GS enzyme dysregulation, driving HS pathogenesis. We therefore sought to explore NCSTN expression in HS skin and the activity of GS in HS-derived fibroblasts. 

Methods: Immunofluorescence (IF) was used to quantify NCSTN protein in HS and healthy skin samples. For in vitro experiments, fibroblasts were derived from HS surgical specimens or axillary biopsies from healthy volunteers. Fibroblasts were maintained in culture for RNA, protein, and enzymatic analysis. TNFα treatment was used to induce inflammatory signaling. As a positive control for NCSTN loss, normal fibroblasts were treated with NCSTN siRNA (siNCSTN). To explore changes in GS kinetics, we used a Förster Resonance Energy Transfer (FRET) assay with an artificial APP-like FRET peptide. Fibroblast membrane fractions containing GS were incubated with FRET peptide for 6 hours in a microplate reader, with fluorescence recorded every 5 minutes. 

Results: Acquired HS patients had lower levels of NCSTN protein in dermal fibroblasts but not epidermal keratinocytes by IF (fibroblast p=0.0007, keratinocyte p=0.854; n=8 HS and 3 control). In normal fibroblasts in vitro, expression of NCSTN mRNA increased upon treatment with TNFα (n=6, p< 0.001). NCSTN protein was also increased (n=3, p< 0.01). GS-mediated cleavage of FRET peptide showed no difference in activity compared to normal fibroblasts (n=8). The knockdown of NCSTN expression did not modify FRET peptide cleavage in normal fibroblasts. Notably, siNCSTN fibroblasts had higher IL-8 expression (p < .0001, n = 10 over 4 experiments).

Conclusion: HS fibroblasts have lower NCSTN levels than healthy controls by IF and Western blot. Normal fibroblasts have increased NCSTN expression when stimulated with TNFα. Interestingly, while GS activity for an APP substrate was not altered in HS fibroblasts or in normal fibroblasts after NCSTN knockdown, increases in the inflammatory chemokine IL-8 were observed. These findings suggest that GS dysfunction in dermal fibroblasts may contribute to inflammation in familial and non-familial HS. Future studies should assess the etiology of NCSTN loss in HS and alterations in GS activity for key substrates including full-length proteins.


Disclosures: K. Williams: None; B. Badiei: None; H. Minsky: None; L. Garza: SPARC, 5, 9.

To cite this abstract in AMA style:

Williams K, Badiei B, Minsky H, Garza L. The Common Form of the Inflammatory Skin Disease Hidradenitis Suppurativa Is Associated with Low Nicastrin Expression in Dermal Fibroblasts [abstract]. Arthritis Rheumatol. 2024; 76 (suppl 9). https://acrabstracts.org/abstract/the-common-form-of-the-inflammatory-skin-disease-hidradenitis-suppurativa-is-associated-with-low-nicastrin-expression-in-dermal-fibroblasts/. 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 ACR Convergence 2024

ACR Meeting Abstracts - https://acrabstracts.org/abstract/the-common-form-of-the-inflammatory-skin-disease-hidradenitis-suppurativa-is-associated-with-low-nicastrin-expression-in-dermal-fibroblasts/

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