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Scientific Oral Presentations

Laryngology/Broncho-Esophagology

Session: Scientific Oral Presentations 3 - Laryngology/Broncho-Esophagology

Characterizing Antigen-Specific T-Cell Activation in GPA Airway Scar

Monday, September 30, 2024
9:54 AM – 10:00 AM EDT
Location: MBCC, 224
Disclosure(s):
Wenda Ye, MD:

faculty for this accredited education activity has no relationship(s) with ineligible companies to disclose.

Ruth J. Davis, MD:

faculty for this accredited education activity has no relationship(s) with ineligible companies to disclose.

Introduction: Granulomatosis with polyangiitis (GPA) is a rare autoimmune small-vessel vasculitis. Up to 20% of patients with GPA experience proximal airway manifestations of disease and often require repeated procedures to relieve airway obstruction. Although progress has been made in the systemic treatment of GPA, the pathogenesis of airway disease in GPA remains unknown.

Methods: Mucosal biopsies of airway scar in GPA (n = 10), iatrogenic laryngotracheal stenosis (iLTS, n = 6), idiopathic subglottic stenosis (iSGS, n = 7) and healthy controls (n = 7) were acquired during routine operative interventions and processed for single cell RNA sequencing (scRNAseq). GPA T-cell receptor (TCR) repertoire diversity was quantified using the RECON algorithm, and the predicted antigenic targets of the repertoire were explored using the GLIPH2 pipeline.

Results: The subglottic mucosa of GPA patients had abundant infiltrating immune cell subsets. The TCR repertoire structure in GPA patients was similar to that of iSGS, iLTS, and healthy controls with a single high frequency (dominant) clonotype that was not shared between patients. There were no differences in repertoire diversity between groups via Hill framework quantitation (p > 0.05). GPA similarity network analysis using GLIPH2 demonstrated several TCR motifs unique to GPA that were not shared with either iSGS, iLTS, or healthy controls.

Conclusions: Proximal airway scar in GPA patients has abundant infiltrating immune cells. The TCR repertoire structure of the mucosal T cells in the affected proximal airway is identical among GPA, iSGS, iLTS, and healthy controls. TCR repertoire diversity was not significantly different between GPA, iSGS, iLTS and healthy controls. However, interrogation of the target in the T cell response in GPA using network similarity analysis via GLIPH2 demonstrated several motifs unique to GPA that were shared between patients. Further study is needed to elucidate specific antigen targets of the observed motifs.

    Presenting Author(s)

  • Wenda Ye, MD

    Resident
    Vanderbilt University Medical Center
    Nashville, TN, United States

    Disclosure(s):

    faculty for this accredited education activity has no relationship(s) with ineligible companies to disclose.

    • Co-Author(s)

  • EC

    Evan A. Clark, BS

    Research Assistant
    Vanderbilt University Medical Center
    Nashville, TN, United States

    Disclosure information not submitted.

  • ET

    Edward Talatala, BS

    Vanderbilt University Medical Center, United States

    Disclosure information not submitted.

  • RD

    Ruth J. Davis, MD

    Assistant Professor
    University of Wisconsin School of Medicine and Public Health
    Madison, WI, United States

    Disclosure(s):

    faculty for this accredited education activity has no relationship(s) with ineligible companies to disclose.

  • MR

    Marisol Ramirez-Solano, MS

    Statistical Genetic Analyst III
    Vanderbilt University Medical Center, United States

    Disclosure information not submitted.

  • QS

    Quanhu Sheng, PhD

    Vanderbilt University Medical Center, United States

    Disclosure information not submitted.

  • CW

    Celestine Wanjalla, MD, PhD

    Assistant Professor of Medicine
    Vanderbilt University Medical Center
    Nashville, TN, United States

    Disclosure information not submitted.

  • SM

    Simon Mallal, MBBS

    Vanderbilt University Medical Center, United States

    Disclosure information not submitted.

    • Senior Author(s)

  • AG

    Alexander H. Gelbard, MD

    Associate Professor
    Vanderbilt University Medical Center
    Nashville, TN, United States

    Disclosure information not submitted.