Sarcoidosis and Immune Cells in Lung, Lymph Nodes and Blood

Studie Av Cellulära Uttryck I Lymfkörtlar, Lungsköljvätska Och Blod Vid Sarkoidos.

Background:

Sarcoidosis is an inflammatory disease, most commonly affecting the lungs and intrathoracic lymph nodes but can affect virtually any organ, sometimes manifesting as life threatening cardiac arrythmias. Some patients resolve spontaneously, whereas others get a chronic disease leading to for instance impaired lung function and cardiac failure. The most severe cases might need a transplantation.

In the lungs, activated T cells are accumulated leading to release of cytokines, especially TNF-alpha is regarded as crucial for disease progression. Some segments of the T cell receptor and specific genes (HLA types) are connected to a resolving disease. More detailed knowledge about mechanisms why some experience a chronic disease course and others resolve spontaneously without treatment is to a large extent lacking. There is no cure, and despite treatment with immunosuppressants (often corticosteroids and cytotoxic agents), many patients experience a deteriorating disease.

Aim:

1. Find biomarkers to be able to early predict which patients will develop a more severe/ chronic disease course and thereby enabeling early intervention before irreversible damage.
2. Predict which treatment is best for a specific patient, i.e. individualize treatment.
3. Find targets for new potential therapies.

Methods:

The majority of data is collected at investigations normally performed during diagnostic work-up for sarcoidosis. Most patients undergo a bronchoscopy with bronchoalveolar lavage (BAL) and some also lymph node punction through oesophagus with the help of ultrasound. The BAL fluid that remains after clinical analysis is used for research purpose. For patients undergoing lymph node punction, one extra punction is performed for research purpose. Extra blood samples are taken from all patients.

The samples will mostly be used for studying T cells with immunohistochemistry, flow cytometry including activity markers, subtypes and receptors, but also cytokines and other cells (for instance B cells, NK and NKT cells). The patients are followed longitudinally, minimum 2 years. Some patients will undergo a second bronchoscopy 6-12 months after the first. Results from the immunological investigations will be correlated to disease course, genetics and result of treatment.

Significance :

By comparing the inflammation in several compartments (lung, lymph node , blood) at a molecular level with clinical disease course, genotype, and treatment response we hope to find biomarkers that can predict disease course and response to therapy. Thereby, we hope to be able to tailor therapy for each individual patient. By studying several compartments, the results may also help to improve understanding of how a systemic inflammation is distributed within the body, and thus also contribute to understanding of other inflammatory diseases.

Study Overview

• Status: Recruiting
• Conditions: Sarcoidosis
• Intervention / Treatment: Diagnostic test: Lymph node puncture, bronchoscopy

• Study Type: Interventional
• Enrollment (Estimated): 560
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Susanna Kullberg, MD; Phone Number: +46 070-2715639; Email: susanna.kullberg@ki.se

Study Locations

• Sweden
  • Stockholm, Sweden
    • Recruiting
    • Karolinska University Hospital
    • Contact: Susanna Kullberg, MD; Phone Number: +46 070-2715639; Email: susanna.kullberg@ki.se

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 90 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Suspicion of sarcoidosis
• Swedish speaking
• Able to understand and approve of study protocol
• No contraindications for planned interventions

Exclusion Criteria:

• No suspicion of sarcoidosis
• Not Swedish-speking
• Not able to understand study protocol
• Not approving of stydy protocol
• Contraindications for planned interventions

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Immune cells; Lymph node puncture and/ or bronchoscopy.	Diagnostic test: Lymph node puncture, bronchoscopy; Included patients will undergo an extra lympn node punction through oesophagus and/ or an extra bronchoscopy.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Immune cell percentages in lung, lymph nodes and blood	Is there a difference in frequency of different immune cells (percentage) between different compartments in clinical disease phenotypes?	2 years

Collaborators and Investigators

• Sponsor: Region Stockholm
• Collaborators: Karolinska Institutet

Study record dates

Study Major Dates

• Study Start (Actual): October 1, 2019
• Primary Completion (Estimated): May 1, 2034
• Study Completion (Estimated): May 1, 2034

Study Registration Dates

• First Submitted: February 6, 2023
• First Submitted That Met QC Criteria: February 20, 2023
• First Posted (Actual): March 2, 2023

Study Record Updates

• Last Update Posted (Actual): October 4, 2024
• Last Update Submitted That Met QC Criteria: October 2, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Immune System Diseases; Lymphoproliferative Disorders; Lymphatic Diseases; Hypersensitivity; Hypersensitivity, Delayed; Sarcoidosis
• Other Study ID Numbers: K2019-6557

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No