Thinking toward improved treatments of systemic lupus erythematosus

Excerpt

In 2012, recommended therapies for SLE include antimalarials, glucocorticoids, azathioprine, mycophenolate mofetil (or myfortic acid), cyclophosphamide, and other immunosuppressants. Belimumab has been added recently. Most are targeted toward adaptive immune responses. We now suspect that several pathways in innate immunity are also critical to driving SLE, including dendritic cells (major source of IFNα), and monocyte/macrophages that appear central in the damage that occurs to renal tissue in lupus nephritis. Abnormalities in neutrophils may also drive IFNα production and damage to endothelial cells. Therefore, treatments that modify these innate immune cells are of great interest. Antimalarials primarily suppress antigen-presenting cells (APC), including TLR activation; clinically they suppress disease activity and damage, but not strongly. Glucocorticoids suppress DC, monocytes and lymphocytes, with reduction of trafficking of proinflammatory cells to target tissues, but they are quite toxic. Belimumab is directed primarily at prevention of B-cell maturation and has clinical benefits that are not large when added to standard therapies. …