Clinical trial NCT06396910: TB and Sarcoidosis Granuloma
Official title: Immune Maping of Tuberculosis and Sarcoidosis Granuloma
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Tuberculosis
Sarcoidosis
Lead sponsor: Karolinska Institutet
Sponsor class: OTHER
First posted: 2024-05-02
Enrollment: 20
Sex: ALL
Minimum age (years): 10
Maximum age (years): 75
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: CASE_ONLY
Time perspective: RETROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: We utilized retrospective historical samples of patients either with TB or sarcoidosis from the Aga Khan University Hospital Clinical Laboratories, Karachi, Pakistan (TB: n=10), the BioMaterialBank North, Research Center Borstel, Germany (sarcoidosis, n=7; TB=1) and the Karolinska University Hospital (Sarcoidosis, n=4). The FFPE samples used were originally obtained for diagnostic purposes.

Brief summary: Tuberculosis (TB) and sarcoidosis are both granulomatous diseases. Here we compared the immunological micro-environments of granulomas from TB and sarcoidosis patients using in situ sequencing (ISS) transcriptomic analysis and multiplexed immunolabelling of tissue sections.

Detailed description: Tuberculosis (TB) and sarcoidosis are diseases that are characterized by the formation of inflammatory structures called granulomas. TB is caused by infection with the bacteria Mycobacterium tuberculosis while sarcoidosis is a an inflammatory disease of unknown ethiology. We hypothesize that the localization of immune molecules in granulomas determines the the course of TB and sarcoidosis using in situ sequencing, a spatial transcriptomic technology and immunolabelling in biopsies from patients. In the project, we aim to answer the following questions: 1. How does the immune landscape differ in different TB granulomas (with/without necrosis, different histology)? 2. How does the immune landscape differ in acute (Lofgren's syndrome) and chronic (non-Lofgren's syndrome) sarcoidosis samples? 3. How does the immune landscape differ in histologically similar granulomas from TB and sarcoidosis patients? We will use in situ sequencing that can identify the exact location of 65 specific immune markers in the lung at the same time, thereby correlating defined immune landscapes with the histology, bacterial content and disease type.

Eligibility criteria: Inclusion Criteria:

Specimen were taken from patients with a confirmed diagnosis of TB based on granulomatous inflammation based on histopathological confirmation together with additional parameters such as, clinical symptoms, radiological and laboratory parameters (microscopy detection of acid-fast bacilli in sputum, M. tuberculosis culture, chest radiography, and MTB/RIF GeneXpert analysis) were included.

Sarcoidosis and TB biopsies were selected by a clinical patholologist that evaluated the ocurrence of the granulomatous lessions

Primary outcomes:
measure: Spatial transcriptome of lung lesions of sarcoidosis and tuberculosis patients
timeFrame: 14 days
Secondary outcomes:
Other outcomes:
Locations:
city: Stockholm
country: Sweden
facility: Karolinska Institutet
Study officials:
References:
citation: Carow B, Muliadi V, Skalen K, Yokota C, Kathamuthu GR, Setiabudiawan TP, Lange C, Scheu K, Gaede KI, Goldmann T, Pandita A, Masood KI, Pervez S, Grunewald J, Hasan Z, Levin M, Rottenberg ME. Immune mapping of human tuberculosis and sarcoidosis lung granulomas. Front Immunol. 2024 Feb 7;14:1332733. doi: 10.3389/fimmu.2023.1332733. eCollection 2023.