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: 1506

Correction of Sjögren’s Syndrome Fluid Secretion Deficits in Salivary Gland Acinar Cells by Aquaporin-1 Gene Transfer

Paola Perez1, Blake Warner2, Sandra Wainer1, Youngmi Ji1, Thomas Pranzatelli1 and Jay Chiorini1, 1Nidcr, National Institute of Health, Bethesda, MD, 2National Institute of Dental and Craniofacial Research, Bethesda

Meeting: ACR Convergence 2020

Keywords: Gene Expression, gene therapy, immunology, Sjögren's Syndrome

  • 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 8, 2020

Title: Sjögren’s Syndrome (1502–1506)

Session Type: Abstract Session

Session Time: 5:00PM-5:50PM

Background/Purpose: The hallmark clinical complaints in Sjögren’s syndrome (SS) are dry mouth and dry eyes related to salivary and lacrimal glands dysfunction. Reduced salivation reflects underlying fluid secretion deficits in the membrane permeability of acinar cells. In several animal models, including SS, increasing the membrane permeability using gene transfer of human aquaporin 1 (hAQP1) effectively restores fluid secretion. Indeed, hAQP1 gene transfer improved salivation and dry mouth in patients with radiation-induced xerostomia. Presently, there are no long-term effective therapies for most patients with dry mouth. To address this unmet clinical need we tested the ability of ex vivo adeno-associated virus serotype-2 (AAV2)-hAQP1 gene transfer to restore fluid secretion in human labial salivary glands (LSG) from SS patients and identify predictive molecular signatures of responsiveness. We hypothesize that by restoring water permeability in acinar cells of salivary glands it is possible to correct salivary hypofunction in SS.

Methods: Sixteen (N=16) subjects provided informed consent and were evaluated in the NIDCR Sjögren’s Syndrome Clinic. Subjects received comprehensive rheumatologic, ophthalmologic, and oral/salivary evaluations including LSG biopsies; nine subjects met the 2016 American College of Rheumatology SS criteria. LSG biopsies were divided into RNAlater for storage or immediately micro-dissected into lobule preparations for ex vivo culture. Lobules were transferred to 24-well transwell plates and cultured at the air-media interface. Two hours after equilibration, LSG lobules were transduced with 6.25E+11 particles of AAV2-hAQP1 and 1.35E+11 AAV2-mCherry or 1.35E+11 AAV2-mCherry alone as a control. After 24 hours of transduction, the volume change response to 2uM carbachol was measured. Remaining lobules were fixed in 4% paraformaldehyde for immunofluorescence (IF) or preserved in RNAlater for RNA sequencing.

Results: AAV2-hAQP1 transduction corrected both SS (p = 0.02) and non-SS (p < 0.01) LSG fluid secretion deficits up to 80% of normal. AAV2-hAQP1 transduction was confirmed using IF for hAQP1 expression and mCherry fluorescence in the acinar tissues. The RNA-sequencing analysis showed that responders to AQP1 transduction have a lower molecular signature for mesenchymal markers.

Conclusion: Our data suggest that, in the context of SS pathophysiology with sufficient secretory parenchyma in the glands of patients, SS salivary hypofunction can be recovered using AAV2-hAQP1.


Disclosure: P. Perez, None; B. Warner, None; S. Wainer, None; Y. Ji, None; T. Pranzatelli, None; J. Chiorini, None.

To cite this abstract in AMA style:

Perez P, Warner B, Wainer S, Ji Y, Pranzatelli T, Chiorini J. Correction of Sjögren’s Syndrome Fluid Secretion Deficits in Salivary Gland Acinar Cells by Aquaporin-1 Gene Transfer [abstract]. Arthritis Rheumatol. 2020; 72 (suppl 10). https://acrabstracts.org/abstract/correction-of-sjogrens-syndrome-fluid-secretion-deficits-in-salivary-gland-acinar-cells-by-aquaporin-1-gene-transfer/. 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 2020

ACR Meeting Abstracts - https://acrabstracts.org/abstract/correction-of-sjogrens-syndrome-fluid-secretion-deficits-in-salivary-gland-acinar-cells-by-aquaporin-1-gene-transfer/

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