MoMa Signature During Granulomatosis

NCT05916638 | Recruiting

• 2 other identifiers: APHP2302732022-A02637-36
• Study Type: observational
• Target: 100
• Locations: 1 country
• Sites: 1

Brief Summary

Sarcoidosis is a systemic inflammatory disease characterized by unspecific granuloma formation. Our hypothesis is that granuloma formation and maintenance mainly relies on the overactivation of monocytes (Mo) and macrophages (Ma). To this end, the study aims (i) to define MoMa systemic signature in sarcoidosis, (ii) to characterize this signature in situ on tissue samples, and (iii) to identify causative factors that participate to the MoMa chronic overactivation. Thus, a cohort of sarcoidosis patients will be compared with tuberculosis patients. The MoMa systemic signature will be defined on whole blood (TruCulture model) and then in situ through different methods (multi-parameter spectral flow cytometry, RNA-seq, Luminex, imaging mass cytometry). The epigenome of monocytes will be studied thanks to CUT\&Tag. The MoMa systemic signature will be defined ex vivo at different time points during the course of the disease with phenotypic, transcriptomic, cytokine and functional approaches. The previously identified signature will be studied in situ and completed by the characterization of granuloma architecture and microenvironmental interactions, which could be modulated by epigenetic modifications. Hence, the epigenome of monocytes will be analyzed in two groups (sarcoidosis and tuberculosis). These results would allow to better understand sarcoidosis physiopathology and, in fine, may raise new therapeutic strategies. Finally, the study could challenge the dogma on innate immunity/auto-inflammation versus adaptive immunity/auto-immunity/memory.

Conditions

Sarcoidosis; Tuberculosis

Keywords

tuberculosis; sarcoidosis; granuloma; monocytes; macrophages

Outcome Measures

Primary Outcomes (8)

• macrophage activation in sarcoidosis measured by epigenomic

  performed on peripheral blood mononuclear cells (PBMCs) isolated from peripheral blood

  up to 12 months of follow-up.

• monocyte activation in sarcoidosis measured by epigenomic

  performed on peripheral blood mononuclear cells (PBMCs) isolated from peripheral blood

  up to 12 months of follow-up.

• macrophage activation in sarcoidosis measured by spatial transcriptomics

  performed on peripheral blood mononuclear cells (PBMCs) isolated from peripheral blood

  up to 12 months of follow-up.

• monocyte activation in sarcoidosis measured by spatial transcriptomics

  performed on peripheral blood mononuclear cells (PBMCs) isolated from peripheral blood

  up to 12 months of follow-up.

• monocyte activation in sarcoidosis measured by transcriptomic

  performed on peripheral blood mononuclear cells (PBMCs) isolated from peripheral blood

  up to 12 months of follow-up.

• macrophage activation in sarcoidosis measured by transcriptomic

  performed on peripheral blood mononuclear cells (PBMCs) isolated from peripheral blood

  up to 12 months of follow-up.

• macrophage activation in sarcoidosis measured by cytokine measurement

  performed on peripheral blood mononuclear cells (PBMCs) isolated from peripheral blood

  up to 12 months of follow-up.

• monocyte activation in sarcoidosis measured by cytokine measurement

  performed on peripheral blood mononuclear cells (PBMCs) isolated from peripheral blood

  up to 12 months of follow-up.

Secondary Outcomes (6)

• monocyte activation in tuberculosis measured by epigenomic

  up to 12 months of follow-up.

• Identification of a pathogen that triggers sarcoidosis development by metagenomic study

  Samples collected before treatment/at diagnosis

• identification of epigenetic modifications of monocytes by CUT&Tag method

  12 months of follow-up.

• Identification of a diagnostic test to discriminate sarcoidosis and tuberculosis

  Samples collected before treatment/at diagnosis

• real-time analysis of oxidative phosphorylation of monocyte

  up to 12 months of follow-up

Study Arms (2)

Sarcoidosis

patients diagnosed with sarcoidosis

Other: blood sample

Tuberculosis

patients diagnosed with tuberculosis

Other: blood sample

Interventions

blood sample OTHER

blood sample collection

Sarcoidosis; Tuberculosis

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Adult patients diagnosed with sarcoidosis or tuberculosis

You may qualify if:

• Male and female \> 18 years old
• Diagnosis of sarcoidosis and of tuberculosis
• Affiliated to medical insurance

You may not qualify if:

• HIV infection
• pregnant or breastfeeding woman
• Patient under legal protection, guardianship or curators

Sponsors & Collaborators

• Assistance Publique - Hôpitaux de Paris: lead

Study Sites (1)

Hôpital Bichat

Paris, 75018, France

RECRUITING

Biospecimen

Retention: SAMPLES WITH DNA

blood, lung biopsy and Bronchoalveolar fluid

MeSH Terms

Conditions

Sarcoidosis; Tuberculosis; Granuloma

Interventions

Blood Specimen Collection

Condition Hierarchy (Ancestors)

Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Hypersensitivity, Delayed; Hypersensitivity; Immune System Diseases; Mycobacterium Infections; Actinomycetales Infections; Gram-Positive Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Infections; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Specimen Handling; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Punctures; Surgical Procedures, Operative; Investigative Techniques

Study Officials

• Karim SACRE, MD-PhD, PU-PH

  Assistance Publique Hopitaux de Paris

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Karim Sacre, MD-PhD, PU-PH

CONTACT

0140256019; karim.sacre@aphp.fr

Darragh DUFFY, PhD

CONTACT

0144389334; darragh.duffy@pasteur.fr

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 17, 2023
• First Posted: June 23, 2023
• Study Start: January 15, 2024
• Primary Completion (Estimated): January 1, 2029
• Study Completion (Estimated): January 1, 2030
• Last Updated: March 3, 2026

Record last verified: 2026-02

Locations

FR (1)