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Publications

Journal Article Epublish

PubMed: 42609693 DOI: 10.1183/23120541.01521-2025

Systemic and local lymph node inflammation at disease onset in sarcoidosis patients.

ERJ Open Res 12(4)

Authors: Marie Robert, Laure Boizeau, Pierre Cappy, Etienne Villain, Slobodan Culina, Aurélie Sannier, Nader Yatim, Arthur Mageau, Nicolas Charles, Christophe Rodriguez, Nathan Peiffer-Smadja, Raphaël Borie, Darragh Duffy, Paul-Louis Woerther, Karim Sacré

Affiliations

  • Translational Immunology Unit, Institut Pasteur, Université Paris-Cité, Paris, France.
  • Assistance Publique Hôpitaux Paris (AP-HP), Département de Médecine Interne, Hôpital Bichat, Paris, France.
  • INSERM UMR1149, CNRS EMR8252, Centre de Recherche sur l'Inflammation, Inidex- Laboratoire d'Excellence Infibrex, Université Paris-Cité, Paris, France.
  • Genobiomics platform, Henri Mondor Hospital (AP-HP), University of Paris-Est, Créteil, France.
  • Team "Viruses, Hepatology, Cancer", Institut Mondor de Recherche Biomédicale, INSERM U955, Créteil, France.
  • scBiomarkers UtechS, Institut Pasteur, Université Paris-Cité, Paris, France.
  • AP-HP, Hôpital Bichat, Département d'Anatomopathologie, Université Paris-Cité, Paris, France.
  • AP-HP, Hôpital Bichat, Département des Maladies Infectieuses, Université Paris-Cité, Paris, France.
  • UMR Inserm 1149, CRI, Hôpital Bichat, AP-HP, Service de Pneumologie Allergologie et Transplantation, Centre Constitutif du Centre de Référence des Maladies Pulmonaires Rares, FHU INFIRE, Université Paris Cité, Paris, France.
  • These authors contributed equally.

Abstract

BACKGROUND

Sarcoidosis is a chronic granulomatous disease of unknown origin, and the potential involvement of microorganisms has long been debated. We conducted the present study to explore the role of microorganisms at the onset of the disease using shotgun sequencing on lymph node samples.

METHODS

We conducted a prospective cohort study of adult patients admitted for sarcoidosis in the department of internal medicine from a tertiary referral university hospital in France (ClinicalTrials.gov identifier NCT05916638). Plasma and tissue samples were collected from sarcoidosis patients prior to the initiation of treatment. Plasma controls were healthy individuals. Tissue sample controls were patients with metastatic adenocarcinoma who underwent lymph node biopsy procedures for cancer staging.

RESULTS

Plasma samples were collected from 19 patients with sarcoidosis and 10 control subjects. Of the 45 proteins studied using a multiplex quantification assay, the levels of 29 were significantly higher in the sarcoidosis patients. Of these, C-X-C motif chemokine ligand 9, lymphotoxin-α and tumour necrosis factor were also significantly upregulated at the mRNA level in affected tissues. Unbiased transcriptomic analysis of lymph node tissue revealed enrichment of the interferon (IFN)-γ signalling pathway, the interleukin (IL)-2-STAT5 pathway and the IL-6-JAK-STAT3 pathway in sarcoidosis patients. Shotgun sequencing of the lymph nodes showed no evidence of bacteria, fungi, viruses or parasites in the sarcoidosis samples.

CONCLUSION

Our findings challenge the long-held belief that sarcoidosis is caused by a microorganism. The activation of the JAK-STAT and IFN-γ signalling pathways in sarcoidosis tissue indicates that JAK inhibitors could be used to treat the condition.

MeSH

Lymph Nodes, Sarcoidosis, Lymph, Tissues