Immunological Mechanisms in Sarcoidosis

Immunologiska Mekanismer Vid Sarkoidos

There is no cure for the inflammatory disease sarcoidosis. Virtually any part of the body can be affected but most often the lungs and lymph nodes. Outcomes after diagnosis vary widely among sarcoidosis patients, with some experiencing resolving disease and others developing chronic disease and lung fibrosis. Cardiac sarcoidosis can lead to life threatening arrythmias and calcium metabolism disturbances can lead to renal impairment.

Treatment with different forms of immunosuppressants are usually tried to dampen symptoms but are not effective in all patients. Furthermore, the disease usually flares up after cessation of treatment. The variability in diseae course and treatment response is thought, at least to some degree, to be explained by individual differences in genetics, immune cells and signaling pathways. But existing evidence is limited. In other inflammatory diseases the gut microbiome is of importance for disease course but its role in sarcoidosis has not been clarified.

In this prospective project the investigators will study genes, inflammatory cells and signaling molecules in the lung, upper airways and blood, and to some extent microbes, also in faeces. Healthy volunteers will be included for comparative studies. Most samples will be taken during normal diagnostic work-up and follow-up of patients with/with suspected sarcoidosis. The findings will be correlated to disease course and effects of different treatments. By linking to national health data and demographic registries, comorbidities and environmental factors will be correlated to data.

By this, the investigators hope to improve understanding of which genes, cells and signaling molecules that are of importance for resolving vs non-resolving disease and why some patients respond to a certain treatment and others don´t. The overall goal is to assess and predict sarcoidosis outcomes. We hypothesize that blood-based biomarkers including those taken during routine care as well as novel cell, signaling molecules and genetic markers, in combination with clinical characteristics can be used to predict outcomes, also treatment response, in sarcoidosis. The results can lead to tailored treatment and individual follow-up for each patient with sarcoidosis.

Study Overview

• Status: Recruiting
• Conditions: Sarcoidosis
• Intervention / Treatment: Procedure: peripheral blood sampling, bronchoscopy, upper airway and faeces sampling

• Study Type: Observational
• Enrollment (Estimated): 5000

Contacts and Locations

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

Study Locations

• Sweden
  • Stockholm County
    • Stockholm, Stockholm County, Sweden, 171 76
      • Recruiting
      • Karolinska University Hospital
      • Contact: Susanna Kullberg, MD; Phone Number: +46 070-2715639; Email: susanna.kullberg@regionstockholm.se

Participation Criteria

Eligibility Criteria

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

• Sampling Method: Non-Probability Sample

Study Population

Patients with/with a suspicion of sarcoidosis referred to Department of Respiratory Medicine, Karolinska University Hospital, Stockholm, Sweden. A total of 4600 patients are planned to be included during 10 years (460/year).

Healthy volunteers will be recruited through advertisments (web based platforms within Karolinska Institutet, magazines, notice-boards). A total of 400 are planned to be included during 10 years (40/year).

Description

Inclusion Criteria:

• Suspicion of sarcoidosis
• Swedish speaking
• Able to understand and approve of study protocol
• No contraindications for planned interventions
• For inclusion of healthy controls they need to be healthy and the same criteria as listed above for patients.

Exclusion Criteria:

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

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort

Intervention / Treatment

Sarcoidosis patients; This study only consists of one arm. The investigators follow patients prospectively and observe clinical parameters including disease course (resolving, non-resolving, which organs are involved, inflammatory markers, chest X-ray etc) and effect of treatment. In this respect the study is observational. However, the patients undergo repeated peripheral blood samples and some also undergo sampling from upper airways, faeces and a bronchoscopy and hence, the study falls in the interventional category

Procedure: peripheral blood sampling, bronchoscopy, upper airway and faeces sampling; Repeated peripheral blood sampling at diagnostic and follow-up visits, in total a maximum of 400 ml/year but never more than 100 ml/ month.; Upper airway sampling wih swab, aspirate and curettage, maximum 3 times/year.; Faeces sampling, the patients do this themselves and leave it to the research unit, maximum 3 times/year.; Bronchoscopy with lavage and a maximum of 6 mucosal biopsies before and after 6-12 months treatment.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of participants with immunosuppressive treatment	Data on treatment will be collected from the medical record	5 years
Disease activity	This refers to cardiac sarcoidosis and is estimated with PET-CT	3 months and 12 months
Number of participants with resolving vs non-resolving disease	Data will be collected from the medical record wether the disease resolved or not	2 and 5 years from baseline
Number of participants with more than 10% change from enrollment in percent of predicted Forced Expiratory Volume in one second (L/s) at 5 years	Measured with spirometry	Baseline and 5 years
Change from enrollment in Immunoglobulin G (g/L) at 5 years	Measured in serum	Baseline and 5 years
Change from enrollment in fatigue at 5 years	The Fatigue Assessment Scale will be used. Maximum score is 50 and minimum 10. A higher score means more fatigue.More than 22 points means the participant suffers from fatigue and more than 34 extreme fatigue.	Baseline and 5 years
Change from enrollment of radiographic findings at 5 years	Chest X-ray will be classified according to Scadding staging	Baseline and 5 years
Change from enrollment of angiotensin converting enzyme (E/L) at 5 years	Measured in serum	Baseline and 5 years
Change from enrollment of soluble Interleukin Receptor 2 (U/ml) at 5 years	Measured in serum	Baseline and 5 years
Change from enrollment of complete blood cell count (/10x9 L) at 5 years	Measured in blood	Baseline and 5 years
Change from enrollment of creatinine levels (micromol/L) at 5 years	Measured in plasma	Baseline and 5 years
Change from enrollment of C-reactive protein (mg/L) at 5 years	Measured in serum	Baseline and 5 years
Number of patients with more than 10% change from enrollment in percent of predicted Diffusing capacity of the Lungs for Carbon Monoxide (%) at 5 years	Measured with spirometry	Baseline and 5 years
Number of participants with more than 10% change from enrollment in percent of predicted Forced Vital Capacity (L) at 5 years	Measured with spirometry	Baseline and 5 years
Change from enrollment of calcium levels (mmol/L) at 5 years	Measured in serum	Baseline and 5 years

Collaborators and Investigators

• Sponsor: Region Stockholm
• Collaborators: Karolinska Institutet
• Investigators: Principal Investigator: Susanna M Kullberg, MD, Karolinska University Hospital

Study record dates

Study Major Dates

• Study Start (Actual): July 7, 2024
• Primary Completion (Estimated): December 31, 2029
• Study Completion (Estimated): December 31, 2034

Study Registration Dates

• First Submitted: August 12, 2024
• First Submitted That Met QC Criteria: August 26, 2024
• First Posted (Actual): August 28, 2024

Study Record Updates

• Last Update Posted (Actual): March 6, 2026
• Last Update Submitted That Met QC Criteria: March 5, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Immune System Diseases; Hypersensitivity; Lymphatic Diseases; Lymphoproliferative Disorders; Hypersensitivity, Delayed; Hemic and Lymphatic Diseases; Sarcoidosis; Diagnostic Techniques and Procedures; Diagnosis; Surgical Procedures, Operative; Minimally Invasive Surgical Procedures; Diagnostic Techniques, Surgical; Endoscopy; Diagnostic Techniques, Respiratory System; Thoracic Surgical Procedures; Pulmonary Surgical Procedures; Bronchoscopy
• Other Study ID Numbers: K2024-5925

Drug and device information, study documents

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