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Pathogenesis of systemic lupus erythematosus: risks, mechanisms and therapeutic targets
  1. Mary K Crow
  1. Mary Kirkland Center for Lupus Research, Hospital for Special Surgery, New York, New York, USA
  1. Correspondence to Professor Mary K Crow, Mary Kirkland Center for Lupus Research, Hospital for Special Surgery, New York, NY 10021, USA; crowm{at}


Research elucidating the pathogenesis of systemic lupus erythematosus (SLE) has defined two critical families of mediators, type I interferon (IFN-I) and autoantibodies targeting nucleic acids and nucleic acid-binding proteins, as fundamental contributors to the disease. On the fertile background of significant genetic risk, a triggering stimulus, perhaps microbial, induces IFN-I, autoantibody production or most likely both. When innate and adaptive immune system cells are engaged and collaborate in the autoimmune response, clinical SLE can develop. This review describes recent data from genetic analyses of patients with SLE, along with current studies of innate and adaptive immune function that contribute to sustained IFN-I pathway activation, immune activation and autoantibody production, generation of inflammatory mediators and tissue damage. The goal of these studies is to understand disease mechanisms, identify therapeutic targets and stimulate development of therapeutics that can achieve improved outcomes for patients.

  • Lupus Erythematosus, Systemic
  • Polymorphism, Genetic
  • Cytokines
  • Autoantibodies
  • Autoimmunity

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  • Handling editor Josef S Smolen

  • Contributors MKC is responsible for all planning, literature review and writing of this article.

  • Funding MKC is supported by the Benjamin M. Rosen Chair in Immunology and Inflammation Research.

  • Competing interests MKC is an associate editor of Annals of the Rheumatic Diseases. She has consulting relationships with AMPEL BioSolutions, Astra Zeneca, Bristol Myers Squibb, Glaxo Smith Kline and Lilly, and holds a research grant from Gilead Sciences.

  • Provenance and peer review Commissioned; externally peer reviewed.