MoMa Signature During Granulomatosis

Condition(s) studied

Investigational drug(s) / intervention(s)

blood sample: blood sample collection

Study 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.

Eligibility

Primary outcome measure(s)

• macrophage activation in sarcoidosis measured by epigenomic — up to 12 months of follow-up.
  performed on peripheral blood mononuclear cells (PBMCs) isolated from peripheral blood
• monocyte activation in sarcoidosis measured by epigenomic — up to 12 months of follow-up.
  performed on peripheral blood mononuclear cells (PBMCs) isolated from peripheral blood
• macrophage activation in sarcoidosis measured by spatial transcriptomics — up to 12 months of follow-up.
  performed on peripheral blood mononuclear cells (PBMCs) isolated from peripheral blood
• monocyte activation in sarcoidosis measured by spatial transcriptomics — up to 12 months of follow-up.
  performed on peripheral blood mononuclear cells (PBMCs) isolated from peripheral blood
• monocyte activation in sarcoidosis measured by transcriptomic — up to 12 months of follow-up.
  performed on peripheral blood mononuclear cells (PBMCs) isolated from peripheral blood
• macrophage activation in sarcoidosis measured by transcriptomic — up to 12 months of follow-up.
  performed on peripheral blood mononuclear cells (PBMCs) isolated from peripheral blood
• macrophage activation in sarcoidosis measured by cytokine measurement — up to 12 months of follow-up.
  performed on peripheral blood mononuclear cells (PBMCs) isolated from peripheral blood
• monocyte activation in sarcoidosis measured by cytokine measurement — up to 12 months of follow-up.
  performed on peripheral blood mononuclear cells (PBMCs) isolated from peripheral blood

Trial sites (1)

More Assistance Publique - Hôpitaux de Paris trials in France

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