Abstract
The pathogenesis of Systemic Lupus Erythematosus (SLE) is complex and remains poorly understood. Infectious triggers, genetic background, immunological abnormalities and environmental factors are all supposed to interact for the disease development. Familial SLE as well as early-onset juvenile SLE studies make it possible to identify monogenic causes of SLE. Identification of these rare inherited conditions is of great interest to understand both SLE pathogenesis and molecular human tolerance mechanisms. Complement deficiencies, genetic overproduction of interferon-α and apoptosis defects are the main situations that can lead to monogenic SLE.Here, we review the different genes involved in monogenic SLE and highlight their importance in SLE pathogenesis.
Highlights
The pathogenesis of Systemic Lupus Erythematosus (SLE) is complex and remains poorly understood
Systemic lupus erythematosus (SLE) is a complex disease: environmental factors, immunological defects, and genetic factors all play a role in its development
Complement plays a role in T and B cell activation as well, and complement deficiency may upset the balance of lymphoid cell activation[10]
Summary
CNS involvement, photosensitivity Nephritis Multiorgan involvement; glomerulonephritis Photosensitivity and articular involvement; mild or absent renal, neurological or pleuropericardial involvement Malar rash, photosensitivity, arthralgia and Raynaud’s phenomenon Multiorgan involvement. Two unrelated cases of juvenile SLE were reported with a mutation in DNAse type 1 [39], and exhibited very high levels of antinucleosomal antibodies This variant represent a very rare cause of lupus and further exploration in a large UK cohort of 170 SLE patients did not found any mutation [40]. Neutrophils are have been shown to be important in lupus pathogenesis, especially since mature SLE neutrophils are primed in vivo by type I IFN and die upon exposure to SLE-derived anti-ribonucleoprotein antibodies, releasing neutrophil extracellular traps (NETs) which contain DNA as well as large amounts of proteins that facilitate the uptake and recognition of mammalian DNA by plasmacytoid dendritic cells [45]. SLE NETs activate pDCs to produce high levels of IFN-α in a DNA- and Toll-like receptor 9-dependent manner These data might suggest that CYBB and other CGD-related genes could be lupus-susceptibility genes
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