Systemic and local lymph node inflammation at disease onset in sarcoidosis patients
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.
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BibTeX
@article{robert2026systemic,
title = {{Systemic and local lymph node inflammation at disease onset in sarcoidosis patients}},
author = {Marie Robert and Laure Boizeau and Pierre Cappy and Etienne Villain and Slobodan Culina and Aurélie Sannier and Nader Yatim and Arthur Mageau and Nicolas Charles and Christophe Rodriguez and Nathan Peiffer-Smadja and Raphaël Borie and Darragh Duffy and Paul-Louis Woerther and Karim Sacré},
journal = {ERJ Open Research},
year = {2026},
month = jul,
doi = {10.1183/23120541.01521-2025},
url = {https://pasteur.hal.science/pasteur-05764973v1},
note = {CC BY-NC 4.0},
}
RIS
TY - JOUR
TI - Systemic and local lymph node inflammation at disease onset in sarcoidosis patients
AU - Marie Robert
AU - Laure Boizeau
AU - Pierre Cappy
AU - Etienne Villain
AU - Slobodan Culina
AU - Aurélie Sannier
AU - Nader Yatim
AU - Arthur Mageau
AU - Nicolas Charles
AU - Christophe Rodriguez
AU - Nathan Peiffer-Smadja
AU - Raphaël Borie
AU - Darragh Duffy
AU - Paul-Louis Woerther
AU - Karim Sacré
PY - 2026
DA - 2026/07/16
JO - ERJ Open Research
DO - 10.1183/23120541.01521-2025
UR - https://pasteur.hal.science/pasteur-05764973v1
AB - 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.
SN - 2312-0541
ER -