SLE

Question 1

Hallmarks of SLE

Answer 1

Auto-reactive B cell and T cell, deposition of immune complex in tissues, systemic activation of type I IFN signaling and cytokines

Question 2

Hallmarks of SLE

Answer 2

Antibody against nucleic acid, especially those against naked and nucleosome-associated dsDNA, RNA/RBP; IFN signatures in blood and affected tissues

Question 3

FDA approved SLE drug?

Answer 3

1. Monoclonal antibody against the interferon-induced B cell proliferation and differentiation factor BAFF
2. Monoclonal antibody blocking type I IFN receptor 1 subunit

Question 4

Mechanisms of dsDNA exposure and clearance in normal cells?

Answer 4

1. Cell death - apoptosis: during apoptosis, chromatin DNA is digested intracrllularly by DNA fragmentation factor DFFB; nucleosides are then either leased as cell-free monomers/polymers, or incorporated into membrane-coated vesicles or micro particles which are all eventually find in plasma; micro particles expose nucleosides on their surface and trigger extracellular digestion by DNase 1 and phagocytosis by phagocytes, and remaining dsDNA is degraded by DNase 2
2. NETosis: granulocytes such as neutrophils expose dsDNA when they die by NETosis
3. Inside the cell: reverse transcription of retro elements; DNA and DNA/RNA hybrid are digested by the 3’ exonuclease TREX1