1. Nat. Rev. Nephrol. doi:10.1038/nrneph.2017.85
Figure 3 Therapeutic targets in systemic lupus erythematosus (SLE) and lupus nephritis
Figure 3 | Therapeutic targets in systemic lupus erythematosus (SLE) and lupus nephritis. Greater understanding of the pathogenic processes underlying lupus nephritis has led to the identification of new therapeutic targets. B cells have a critical role in the pathogenesis of SLE, and B-cell depletion therapy therefore remains an attractive therapeutic option. The anti-CD20 antibody, rituximab, can deplete autoreactive B cells and thereby attenuate the production of autoantibodies involved in disease manifestations. The B-cell-activating factor (BAFF)-neutralizing antibody, belimumab, was shown to reduce renal flares and proteinuria in patients with SLE. Other promising B cell-depleting monoclonal antibodies, such as tabalumab and epratuzumab, require further testing. Abatacept is a co-stimulatory inhibitor that targets B7-1 (CD80) on the surface of dendritic cells or B cells, and blocks co-stimulation of CD28 on T cells. Inhibitors of the complement system, such as eculizumab and CCX-168 could have therapeutic value in patients with concurrent thrombotic microangiopathy or anti-neutrophil cytoplasmic antibody-associated vasculitis. Calcineurin inhibitors (CNIs) have immune modulatory effects but also direct effects on podocytes, and might be useful in patients with lupus-associated podocyte injury. Inhibition of the apoptosis regulator BCL-2 prevented the development of tubulointerstital inflammation in a mouse model of lupus nephritis. IL-23 activation might have a role in the development of glomerular crescents, suggesting that anti-IL-23 antibodies might be beneficial. Other promising therapies that need further exploration include infliximab, which targets the inflammatory tumour necrosis factor (TNF), sirukumab, which targets inflammatory IL-6, and monoclonal antibodies to interferon (IFN). GBM, glomerular basement membrane; TH17, T helper type 17 cell.
Yu, F. et al. (2017) Redefining lupus nephritis: clinical implications of pathophysiologic subtypes
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