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A Distinguishable Peripheral Blood and Conjunctival Transcriptome and Gut Microbiome in Sjögren's Disease: A Pilot
Robert D Nguyen1, Jeremy Nortey, Elisabeth Gebreegziabher
1Francis I. Proctor Foundation (R.D.N., J.N., E.G., A.H., L.Z., C.C., T.D., T.M.L., J.A.G.), University of California, San Francisco, CA; Department of Ophthalmology (T.D., T.M.L., J.A.G.), University of California, San Francisco, CA; Department of Ophthalmology (J.N.), Northwestern University, Chicago, IL.
This study identified new molecular pathways in Sjögren's disease conjunctiva and confirmed interferon/complement roles in blood. Distinct gut microbiome changes were found, offering potential therapeutic targets for Sjögren's disease.
Area of Science:
- Immunology
- Genomics
- Microbiome research
Background:
- Sjögren's disease is an autoimmune disorder affecting exocrine glands.
- Understanding the molecular basis and microbiome in Sjögren's disease is crucial for developing targeted therapies.
Purpose of the Study:
- To create a multi-tissue molecular atlas of Sjögren's disease using RNA sequencing.
- To identify differentially expressed genes (DEGs) and microbial profiles in Sjögren's disease patients.
- To characterize ocular surface and gut microbiome in Sjögren's disease.
Main Methods:
- High-throughput RNA sequencing was performed on peripheral blood, conjunctival, and rectal swabs.
- Participants included 11 Sjögren's disease patients and 4 non-Sjögren's controls.
- DEGs and microbial profiles were analyzed to differentiate between groups.
Main Results:
- Upregulated type I interferon and complement pathways were found in the peripheral blood of Sjögren's patients.
- Novel conjunctival pathways including intracellular vesicle trafficking, immunometabolism, and cytoskeletal remodeling were identified.
- Distinct gut microbiome profiles, with increased Lactobacillus reuteri, were observed in Sjögren's disease participants.
Conclusions:
- RNA sequencing confirmed known pathways and identified novel molecular signatures in Sjögren's disease.
- Findings expand understanding of Sjögren's disease mechanisms beyond traditional immune pathways.
- Distinct gut microbiome profiles suggest potential therapeutic targets and patient stratification strategies for Sjögren's disease, pending larger cohort validation.
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