Type I interferon in the pathogenesis of systemic lupus erythematosus
M Postal, JF Vivaldo, R Fernandez-Ruiz… - Current opinion in …, 2020 - Elsevier
Current opinion in immunology, 2020•Elsevier
Highlights•Type I IFN is implicated in SLE pathogenesis by multiple lines of evidence,
including genetics and induction of SLE by IFN treatment.•Nucleic-acid sensing pathways
influence the threshold of activation and triggering of type I IFN production.•Abnormalities in
extracellular processing of DNA can enhance type I IFN production.•High type I IFN levels
are associated with nephritis, mucocutaneous manifestations, and the presence of
autoantibodies in SLE.•Anifrolumab, a monoclonal antibody that blocks the type I IFN …
including genetics and induction of SLE by IFN treatment.•Nucleic-acid sensing pathways
influence the threshold of activation and triggering of type I IFN production.•Abnormalities in
extracellular processing of DNA can enhance type I IFN production.•High type I IFN levels
are associated with nephritis, mucocutaneous manifestations, and the presence of
autoantibodies in SLE.•Anifrolumab, a monoclonal antibody that blocks the type I IFN …
Highlights
- Type I IFN is implicated in SLE pathogenesis by multiple lines of evidence, including genetics and induction of SLE by IFN treatment.
- Nucleic-acid sensing pathways influence the threshold of activation and triggering of type I IFN production.
- Abnormalities in extracellular processing of DNA can enhance type I IFN production.
- High type I IFN levels are associated with nephritis, mucocutaneous manifestations, and the presence of autoantibodies in SLE.
- Anifrolumab, a monoclonal antibody that blocks the type I IFN receptor, has shown therapeutic benefit in SLE.
Type I interferon (IFN) is a primary pathogenic factor in systemic lupus erythematosus (SLE). Gain-of-function genetic variants in the type I IFN pathway have been associated with risk of disease. Common polygenic as well as rare monogenic influences on type I IFN have been demonstrated, supporting a complex genetic basis for high IFN in many SLE patients. Both SLE-associated autoantibodies and high type I IFN can be observed in the pre-disease state. Patients with SLE and evidence of high type I IFN have more active disease and a greater propensity to nephritis and other severe manifestations. Despite the well-established association between type I IFN and SLE, the specific triggers of type I IFN production, the mechanisms by which IFNs help perpetuate the cycle of autoreactive cells and autoantibody production are not completely clear. This review provides an updated overview of type I IFN in SLE pathogenesis, clinical manifestations, and current therapeutic strategies targeting this pathway.
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