Functional Analysis of Salivary Glands and Correlation With Sialoscintigraphy in Sjogren's Syndrome

Functional Analysis and Antigen Presentation in Striated Ductal Cells of Salivary Glands and Correlation With Sialoscintigraphy in Patients and Animal Models of Sjogren's Syndrome

Sjögren's syndrome is a complex autoimmune disorder. The investigators hypothesize that striated ductal cells may function as non-professional antigen-presenting cells in Sjögren's syndrome. However, there are currently no established methods to assess the functional status of striated ductal cells or their relationship with clinical presentations. To address this knowledge gap, the investigators aim to investigate the potential of sialoscintigraphy, a non-invasive imaging technique, to evaluate the functional status of striated ductal cells. The sodium iodide symporter (NIS), predominantly expressed in striated ductal cells, facilitates the transport of technetium-99m, a radiotracer used in sialoscintigraphy. The investigators hypothesize that the expression level of NIS, as evaluated through sialoscintigraphy, may serve as an indicator of striated ductal cell function and potentially correlate with clinical manifestations in Sjögren's syndrome. However, the literature and our preliminary data lead us to hypothesize that age and the specific major salivary gland being evaluated may introduce confounding factors in the interpretation of sialoscintigraphy results. The investigators therefore proposed to 1) establish a nomogram of sialoscintigraphy stratified by age and specific salivary glands. The investigators will recruit healthy volunteers to receive sialoscintigraphy for the nomogram; 2) associate the expression level of NIS in the striated ductal cells from the major salivary glands with sialoscintigraphy, markers of antigen presentation, and disease manifestations of Sjögren's syndrome. The outcomes will help further applications of sialoscintigraphy in Sjögren's syndrome and formulate hypotheses to explore the pathological mechanisms underlying Sjögren's syndrome.

Study Overview

• Status: Recruiting
• Conditions: Sjogren's Syndrome
• Intervention / Treatment: Radiation: Sialoscintigraphy

Detailed Description

Sjögren's syndrome is a complex autoimmune disorder characterized by CD4 T lymphocyte infiltration into the salivary glands, leading to impaired glandular function. The mechanisms underlying lymphocyte accumulation and activation in the absence of definitive antigen-presenting cells remain poorly understood. The investigators hypothesize that striated ductal cells, the primary target of lymphocyte invasion, may function as non-professional antigen-presenting cells in Sjögren's syndrome. However, there are currently no established methods to assess the functional status of striated ductal cells or their relationship with clinical presentations. To address this knowledge gap, the investigators aim to investigate the potential of sialoscintigraphy, a non-invasive imaging technique, to evaluate the functional status of striated ductal cells. The sodium iodide symporter (NIS), predominantly expressed in striated ductal cells, facilitates the transport of technetium-99m, a radiotracer used in sialoscintigraphy. The investigators hypothesize that the expression level of NIS, as evaluated through sialoscintigraphy, may serve as an indicator of striated ductal cell function and potentially correlate with clinical manifestations in Sjögren's syndrome. However, the literature and our preliminary data lead us to hypothesize that age and the specific major salivary gland being evaluated may introduce confounding factors in the interpretation of sialoscintigraphy results. Therefore, to address these hypotheses, our research proposal consists of three aims. First, establishing a nomogram of sialoscintigraphy stratified by age and specific salivary glands. The investigators will recruit healthy volunteers to receive sialoscintigraphy for the nomogram. This nomogram will provide a valuable reference for clinical application and further research in interpreting sialoscintigraphy results. Second, associating the expression level of NIS in the striated ductal cells from the major salivary glands with sialoscintigraphy, markers of antigen presentation, and disease manifestations of Sjögren's syndrome. The outcomes will help further applications of sialoscintigraphy in Sjögren's syndrome and formulate hypotheses to explore the pathological mechanisms underlying Sjögren's syndrome. Third, evaluating the capability of antigen presentation in striated ductal cells of salivary glands and to identify potential therapeutic targets. The investigators will examine their ability to uptake extracellular substances and validate their antigen-presenting ability using OT-II cells. Additionally, the investigators will perform RNA sequencing to identify potential therapeutic targets and manipulate their expression to evaluate their impact on the activation of OT-II cells. These findings will confirm that the striated ductal cells as non-professional antigen-presenting cells in Sjögren's syndrome and identify potential therapeutic genetic targets. Overall, our proposed research has the potential to utilize available diagnostic methods to evaluate the striated ductal cells, advance the understanding of how the non-professional antigen-presenting cells participate in the pathogenesis of Sjögren's syndrome, and contribute to the development of innovative therapies.

• Study Type: Interventional
• Enrollment (Estimated): 60
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: CHIAO-FENG CHENG, MD; Phone Number: 0972652625; Email: 103622@ntuh.gov.tw

Study Locations

• Taiwan
  • Taipei, Taiwan, 100
    • Recruiting
    • National Taiwan University Hospital
    • Contact: Chiao-Feng Cheng, MD; Phone Number: 886-972-652-625; Email: 103622@ntuh.gov.tw

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Nomogram: no sicca symptoms
• Sicca: already receiving sialoscintigraphy

Exclusion Criteria (generally):

• pregnancy
• breast feeding
• HIV
• cancer with active treatment

(for nomogram)

• chronic illness needed regular follow-up
• Use anti-histamine, diuretics, anti-depressants, psychotropic medications, anxiolytics or NSAIDs that interfering saliva secretion
• smoking in recent one year
• Positive profiles for anti-SSA or anti-ENA

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: Sialoscintigraphy (healthy control for nomogram); Healthy population for nomogram of sialoscintigraphy	Radiation: Sialoscintigraphy; Sialoscintigraphy
Other: Sialoscintigraphy (sicca patients); Patients with sicca symptoms. Data of sialoscintigraphy retrieved from medical records.	Radiation: Sialoscintigraphy; Sialoscintigraphy

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Quantitative profiles of sialoscintigraphy, including accumulation velocity and secretion velocity	For establishment of sialoscintigraphy nomogram	3 months within enrollment

Collaborators and Investigators

• Sponsor: National Taiwan University Hospital
• Investigators: Principal Investigator: National Taiwan University Hospital, National Taiwan University Hospital

Study record dates

Study Major Dates

• Study Start (Actual): September 1, 2023
• Primary Completion (Estimated): August 1, 2025
• Study Completion (Estimated): August 1, 2025

Study Registration Dates

• First Submitted: July 31, 2024
• First Submitted That Met QC Criteria: July 31, 2024
• First Posted (Actual): August 2, 2024

Study Record Updates

• Last Update Posted (Actual): August 6, 2024
• Last Update Submitted That Met QC Criteria: August 4, 2024
• Last Verified: July 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Immune System Diseases; Autoimmune Diseases; Eye Diseases; Disease; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Connective Tissue Diseases; Arthritis; Stomatognathic Diseases; Mouth Diseases; Lacrimal Apparatus Diseases; Arthritis, Rheumatoid; Xerostomia; Salivary Gland Diseases; Dry Eye Syndromes; Syndrome; Sjogren's Syndrome
• Other Study ID Numbers: 202307135MINB

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No