Lupus nephritis. How latest insights into its pathogenesis promote novel therapies

Abstract

A set of novel drugs have the potential to more specifically interfere with these pathomechanisms and raise hope to more efficiently treat lupus nephritis with fewer side-effects in the near future.

The etiology of glomerulonephritis: roles of infection and autoimmunity

“…109 Activation of the type I IFN pathway results in a 'signature' of specific gene expression that is observed with both viral infections and SLE. 19,23,106,107 Indeed, IFN-a has been shown to be essential for development of SLE in both spontaneous and induced animal models. 106,107 Of the potential viral etiologies that may trigger the disease, the best studied is the EBV.…”

“…19,23,106,107 Indeed, IFN-a has been shown to be essential for development of SLE in both spontaneous and induced animal models. 106,107 Of the potential viral etiologies that may trigger the disease, the best studied is the EBV. 110,111 This virus infects B cells via binding of its viral envelope glycoprotein 350 to the B-cell type 2 complement receptor and remains latent for the life of the individual.…”

“…19,23,104,106 Multiple genes have been incriminated as risk factors, particularly ones that normally assure low levels of DNA or nucleotides in extracellular compartments through opsonization of dead cells, or apoptosis, and genes coding for components of the classical complement pathway. 104,106,107 There is a remarkable similarity between the immune environment in SLE and that stimulated by viral infections, which initiate type I interferon (IFN-a) or IFN-g. 16,38,103,108 In brief, many viruses can induce an immune response by the release of viral ribonucleoprotein and U1 small ribonucleoprotein, which is similar to that observed in SLE. 19,23 These ligands bind TLRs, particularly TLR3, TLR7, and TLR9, to activate the innate immune system and induce type I IFN release by plasmacytoid dendritic cells.…”

Regulatory cell subsets in the control of autoantibody production related to systemic autoimmunity

“…Immune complex deposition is readily detectable in the glomeruli of SLE. The classic hypothesis of circulating immune complex deposits inside the glomerulus was a matter of debate 2 3. It was proposed that DNA immune complex forms in situ by binding to nucleosomes from renal cells4 or mesangial annexin II 5.…”

“…It was proposed that DNA immune complex forms in situ by binding to nucleosomes from renal cells4 or mesangial annexin II 5. Immune complex activates glomerular cells by the ligation of Fc receptor and the nucleic acid component of immune complex activates the renal macrophages and dendritic cells through Toll-like receptors 3. The pathogenecity of SLE immune complex was proved by the observation that passive transfer of human SLE sera into mice expressing human FcγRIIA and FcγRIIB on neutrophils induces lupus nephritis when the mice additionally lack Mac-1 6…”