Figure 1.

The spiral of disease progression in SLE. Individuals with identified genetic polymorphisms are at higher risk for SLE compared to the general population. Environmental triggers also probably contribute to the initiation and perpetuation of the disease. Activation of the innate immune system results in enhanced antigen presentation to T cells and the release of proinflammatory cytokines, including type I IFNs. These changes facilitate activation of the adaptive immune system and the development of autoantibodies. Autoantibodies bind to nucleic acids or cellular debris to form complexes that provide further stimulation to innate immune cells through TLRs. Autoreactive B cells act as antigen-presenting cells for the recruitment of more autoreactive T cells. These positive feedback loops that involve the innate and adaptive immune systems amplify clones of autoreactive lymphocytes during the preclinical stage of SLE. The onset of clinical manifestations is associated with systemic inflammation and injury of target organs, resulting in further amplification of immune activation. SLE becomes increasingly resistant to immune-modulating therapies and may eventually progress to irreversible tissue damage. The events that start to occur before or after the clinical onset are shown in green or blue, respectively.