Details

Autor(en) / Beteiligte

• Simon, Quentin
• Grasseau, Alexis
• Boudigou, Marina
• Le Pottier, Laëtitia
• Bettachioli, Eléonore
• Cornec, Divi
• Rouvière, Bénédicte
• Jamin, Christophe
• Le Lann, Lucas
• Orietta Borghi, Maria
• Aguilar-Quesada, Rocio
• Renaudineau, Yves
• Alarcón-Riquelme, Marta E
• Pers, Jacques-Olivier
• Hillion, Sophie

Titel

A cytokine network profile delineates a common Th1/Be1 pro-inflammatory group of patients in four systemic autoimmune diseases

Ist Teil von

• Arthritis & rheumatology (Hoboken, N.J.), 2021-02

Ort / Verlag

United States: Wiley

Erscheinungsjahr

2021

Link zum Volltext

Quelle

Alma/SFX Local Collection

Beschreibungen/Notizen

• The effector T-cell and B-cell cytokine networks have been implicated in the pathogenesis of systemic autoimmune diseases (SAD), but an exploration of this association with the heterogeneity of clinical manifestations and immune profiles has not been carefully examined. The objective of this study was to examine whether cytokine profiles could delineate distinct groups of patients in four SAD (systemic lupus erythematosus, Sjögren syndrome, rheumatoid arthritis, and systemic sclerosis). 179 patients and 48 healthy volunteers were enrolled in the multi-centric cross-sectional PRECISESADS. Multi-low-dimensional omics data (cytokines, autoantibodies, immune circulating cells) were examined. Co-culture experiments were used to test the impact of the cytokine microenvironment on the T- and B-cell cross-talk. A pro-inflammatory cytokine profile defined by high levels of CXCL10, IL-6, IL-2, and TNF-α characterized a distinct group of patients in the four SAD. In each disease, this pro-inflammatory cluster was associated with a specific immune circulating cell signature, a more severe disease, and higher levels of autoantibodies, suggesting an uncontrolled pro-inflammatory Th1 immune response. We observed in vitro that B cells reinforce Th1 differentiation and naïve T-cell proliferation leading to the induction of B-cell effector type-1 (Be1) cells and IgG production. This process is associated with an increase in CXCL10, IL-6, IL-2, and IFN-γproduction. This composite analysis brings new insights into human B cell functional heterogeneity based on the T/B-cell crosstalk and, on the other hand, proposes a better stratification of SAD patients suggesting that combined biomarkers would be a great value to design personalized treatments.