Table 3:
Summary of Drug Development Findings in Human and Mouse SLE
| Human SLE | Mouse SLE | |||
|---|---|---|---|---|
| TheraDeutic | Immunolosical | Therapeutic | Immunoloeical | |
| Belimumab | ↓ : disease activity, organ system manifestations, incidence and severity of disease flares, steroid-sparing effects ↓ : anti-dsDNA titers |
↓ : naïve, activated, plasmacytoid B cells - : plasma cells, class-switched memory B cells, T cells |
↓ : disease activity, autoantibody production | ↓ : T2, marginal zone, follicular B cells, plasma cells - : T cells |
| MMF | ↓ : disease activity, organ system manifestations, incidence of flares | ↓ : almost all B cell subsets, Th17 and Tres cells ↓ : VEGF, PDGF-BB, CXCL12, CXCL9, B cell and STAT3 pathways - : double-nesative memory B cells |
↓ : disease activity, organ infiltrates and manifestations, Anti-dsDNA levels | Mixed results ↓ : podocyte urokine receptor expression, PKC/fibronectin deposition in glomeruli/interstititium |
| Abatacept | ↓ : anti-dsDNA, complement levels - : efficacy | ↓ : disease activity in patients with high plasma, dendritic, neutrophil, and natural killer cells | ↓ : disease activity, organ manifestations, decreased autoantibody production | ↓ : T and B cell activation/proliferation ↓ : serum IFNg, IL-4, CD11b, CD11c, Gr1, CD21, CD86, MHCII in splenic B cells |
| Rituximab | - : efficacy ↓ : anti-dsDNA, anti- cardiolipin ↓ : complement, BAFF levels |
- : double negative and CD5+ memory B cells ↓ : CD40, CD80 expression on B cells ↓ : activated CD4, CD8, Treg cells |
↓ : disease activity, autoantibody production | ↓ : B cell subsets, T cell activation - : splenic MZ and T2 B cells |
| Anti-IFN | ↓ : disease activity, organ system manifestations, incidence and severity of disease flares, steroid-sparing effects | ↑ : class-switched memory B cells, CD4, CD8, CXCR5 +/- memory cells ↓ : CXCL13, BAFF, CCL19, endothelial cell markers |
↓ : disease activity, organ manifestation, autoantibody production | ↓ : activated T, activated B cells, macrophages, CD40hi pDC |
Symbols: ↓ indicate a decrease or improvement; ↑ indicate an increase; - indicate no change