Pathophysiology of Sjögren's syndrome by Frans G.M. Kroese
Sjögren's is the 2nd most common ARD
Key characteristics include:
Sicca symptoms (dry eyes and mouth)
Extraglandular manifestations
Strong female predominance (9:1 ratio)
No approved treatment yet😔
#EULAR2024 #Sjögrens
Sjögren's is the 2nd most common ARD
Key characteristics include:
Sicca symptoms (dry eyes and mouth)
Extraglandular manifestations
Strong female predominance (9:1 ratio)
No approved treatment yet😔
#EULAR2024 #Sjögrens
Major pathogenic characteristics of Sjögren's
🔬Lymphocytic infiltrates in salivary and lacrimal glands
🔬Germinal center-like structures with B cells
🔬T-cell dependent B-cell hyperactivity
🔬Interferon signature
🔬CD8+ granzyme K+ tissue-resident memory cells
#EULAR2024
🔬Lymphocytic infiltrates in salivary and lacrimal glands
🔬Germinal center-like structures with B cells
🔬T-cell dependent B-cell hyperactivity
🔬Interferon signature
🔬CD8+ granzyme K+ tissue-resident memory cells
#EULAR2024
🔬scRNAseq analysis revealed diverse cell types, including acinar cells (responsible for saliva production), immune cells, and fibroblasts
🔬Acinar cells in Sjögren's patients exhibited:
Fewer, but larger mitochondria
Altered morphology: swollen with abnormal cristae.
#EULAR2024
🔬Acinar cells in Sjögren's patients exhibited:
Fewer, but larger mitochondria
Altered morphology: swollen with abnormal cristae.
#EULAR2024
Turns out, fibroblasts are major signal senders 📣,
while CD8+ T cells are primarily receivers 👂.
The communication pathways between fibroblasts and CD8+ T cells are enriched for chemokines and ECM components.
#EULAR2024
while CD8+ T cells are primarily receivers 👂.
The communication pathways between fibroblasts and CD8+ T cells are enriched for chemokines and ECM components.
#EULAR2024
Granzyme K, released by these CD8+ T cells, has wide-ranging effects:
💥 Endothelial activation
💥 Pro-inflammatory cytokine production
💥 Disrupted Ca++ flux
💥 Mitochondrial damage, releasing mtDNA & driving type I IFN responses
#EULAR2024
💥 Endothelial activation
💥 Pro-inflammatory cytokine production
💥 Disrupted Ca++ flux
💥 Mitochondrial damage, releasing mtDNA & driving type I IFN responses
#EULAR2024
The crosstalk between fibroblasts and CD8+ T cells centers around chemokines and ECM components.
This interaction likely contributes to the early glandular dysfunction seen in Sjögren's.
#EULAR2024
#SjogrensSyndrome
This interaction likely contributes to the early glandular dysfunction seen in Sjögren's.
#EULAR2024
#SjogrensSyndrome
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