title: From mechanism to therapies in systemic lupus erythematosus.
abstract: Systemic lupus erythematosus (SLE) is a disabling and deadly disease. Development of novel therapies for SLE has historically been limited by incomplete understanding of immune dysregulation. Recent advances in lupus pathogenesis, however, have led to the adoption or development of new therapeutics, including the first Food and Drug Administration-approved drug in 50 years.
  
  
  
  Multiple cytokines (interferon, B lymphocyte stimulator, IL-6, and IL-17), signaling pathways (Bruton's Tyrosine Kinase, Janus kinase/signal transducer and activator of transcription), and immune cells are dysregulated in SLE. In this review, we cover seminal discoveries that demonstrate how this dysregulation is integral to SLE pathogenesis and the novel therapeutics currently under development or in clinical trials. In addition, early work suggests metabolic derangements are another target for disease modification. Finally, molecular profiling has led to improved patient stratification in the heterogeneous SLE population, which may improve clinical trial outcomes and therapeutic selection.
  
  
  
  Recent advances in the treatment of SLE have directly resulted from improved understanding of this complicated disease. Rheumatologists may have a variety of novel agents and more precise targeting of select lupus populations in the coming years.
authors.affiliation: aDivision of Rheumatology, Washington University School of Medicine, St. Louis, Missouri bDivision of Immunology/Rheumatology, Stanford University, Palo Alto, California, USA.
authors.forename: Michael A
authors.initials: MA
authors.lastname: Paley
authors.forename: Vibeke
authors.initials: V
authors.lastname: Strand
authors.forename: Alfred H J
authors.initials: AH
authors.lastname: Kim
mesh_terms: D000225:Adenine / Q000031:analogs & derivatives; D000077329:Agammaglobulinaemia Tyrosine Kinase; D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D061067:Antibodies, Monoclonal, Humanized / Q000627:therapeutic use; D053264:B-Cell Activating Factor / Q000276:immunology*; D003499:Cyclic S-Oxides / Q000627:therapeutic use; D016207:Cytokines / Q000276:immunology; D017277:Drug Approval; D055808:Drug Discovery; D006801:Humans; D007155:Immunologic Factors / Q000627:therapeutic use; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D016898:Interferon-alpha / Q000276:immunology*; D020381:Interleukin-17 / Q000276:immunology*; D015850:Interleukin-6 / Q000276:immunology*; D007546:Isoquinolines / Q000627:therapeutic use; D053612:Janus Kinases / Q000276:immunology; D008180:Lupus Erythematosus, Systemic / Q000188:drug therapy / Q000276:immunology*; D010880:Piperidines / Q000627:therapeutic use; D011505:Protein-Tyrosine Kinases / Q000276:immunology; D011720:Pyrazoles / Q000627:therapeutic use; D011743:Pyrimidines / Q000627:therapeutic use; D011993:Recombinant Fusion Proteins / Q000627:therapeutic use; D000069283:Rituximab / Q000627:therapeutic use; D050791:STAT Transcription Factors / Q000276:immunology; D015398:Signal Transduction / Q000276:immunology*
chemical_list: C585580:5-amino-1-(1-cyanopiperidin-3-yl)-3-(4-(2,4-difluorophenoxy)phenyl)-1H-pyrazole-4-carboxamide; D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D053264:B-Cell Activating Factor; D003499:Cyclic S-Oxides; D016207:Cytokines; D007155:Immunologic Factors; D007166:Immunosuppressive Agents; D016898:Interferon-alpha; D020381:Interleukin-17; D015850:Interleukin-6; D007546:Isoquinolines; D010880:Piperidines; D011720:Pyrazoles; D011743:Pyrimidines; C000588993:RN486; D011993:Recombinant Fusion Proteins; D050791:STAT Transcription Factors; C517409:stattic; C551803:ibrutinib; D000069283:Rituximab; C000604955:clazakizumab; C568922:sirukumab; C511911:belimumab; D011505:Protein-Tyrosine Kinases; D000077329:Agammaglobulinaemia Tyrosine Kinase; D053612:Janus Kinases; D000225:Adenine; C524618:TACI receptor-IgG Fc fragment fusion protein; C577244:rontalizumab; C568334:sifalimumab