Skip to main content
SpringerLink
Log in

Therapeutic Modulation of the Interferon Pathway in Systemic Lupus Erythematosus

  • Chapter
  • First Online:
Pathogenesis of Systemic Lupus Erythematosus

  • 445 Accesses

Abstract

Interferons (IFNs), in particular type I IFN, have emerged as key pathogenic cytokines in systemic lupus erythematosus (SLE). The previous Chapter outlined the biology of type I IFN, and evidence for its contribution to disease pathogenesis in SLE. This Chapter will explore the evidence for therapeutic targeting of the IFN pathway in preclinical and clinical trial studies. There are multiple potential avenues to target the IFN pathway therapeutically (Fig. 5.1)—these include neutralizing the IFNs themselves, interfering with stimulators of IFN production such as nucleic acids, and altering the cellular machinery involved in IFN production (such as Toll-like receptors (TLRs), and the Janus Kinase/Signal Transducer and Activator of Transcription (JAK/STAT) signalling pathway). Later phase clinical trials of these agents have mostly used composite disease activity measures as their primary outcomes, and are conducted in patients with at least moderate disease activity (excluding those with severe lupus nephritis and central nervous system lupus), with standard of care (including immunosuppressive agents and anti-malarials) as placebo. Secondary outcome measures often include clinical parameters, steroid sparing effects, and the ability of the drug to suppress an IFN gene signature.

Therapeutics targetting the interferon system in systemic lupus erythematosus. Therapeutics targeting various aspects of the interferon pathway are in different stages of development, ranging from those that target the IFN producing cell, the pDC, to various parts of the IFN signaling machinery. (BDCA—blood dendritic cell antigen, IFN—interferon, JAK—Janus Kinase, pDC—plasmacytoid dendritic cell, STAT—Signal Transducer and Activator of Transcription, TLR—toll-like receptor)

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 89.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 119.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 169.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Braun D, Geraldes P, Demengeot J (2003) Type 1 interferon controls the onset and severity of autoimmune manifestations in lpr mice. J Autoimmun 20:15–25

    Article  PubMed  CAS  Google Scholar 

  2. Santiago-Raber ML, Baccala R, Haraldsson KM, Choubey D, Stewart TA, Kono DH et al (2003) Type-1 interferon receptor deficiency reduces lupus-like disease in NZB mice. J Exp Med 197:777–788

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  3. Kono DH, Baccala R, Theofilopoulos AN (2003) Inhibition of lupus by genetic alteration of the interferon-alpha/beta receptor. Autoimmunity 36(8):503–510

    Article  PubMed  CAS  Google Scholar 

  4. Agrawal H, Jacob N, Carreras E, Bajana S, Putterman C, Turner S et al (2009) Deficiency of type I IFN receptor in lupus-prone New Zealand mixed 2328 mice decreases dendritic cell numbers and activation and protects from disease. J Immunol 183:6021–6029

    Article  PubMed  CAS  Google Scholar 

  5. Baccala R, Gonzalez-Quintial R, Schreiber RD, Lawson BR, Kono DH, Theofilopoulos AN (2012) Anti-IFN-a/b receptor antibody treatment ameliorates disease in lupus-predisposed mice. J Immunol 189:5976–5984

    Article  PubMed  CAS  Google Scholar 

  6. Morand EF, Furie R, Tanaka Y, Bruce IN, Askanase AD, Richez C, et al (2020) TULIP-2 trial investigators. Trial of anifrolumab in active systemic lupus erythematosus. N Engl J Med 16:382(3):211–221

    Google Scholar 

  7. Furie RA, Morand EF, Bruce IN, Manzi S, Kalunian KC, Vital EM et al (2019) Type I interferon inhibitor anifrolumab in active systemic lupus erythematosus (TULIP-1): a randomised, controlled, phase 3 trial. Lancet Rheumatol 1:e208–e219

    Article  Google Scholar 

  8. Yee CS, Farewell V, Isenberg DA, Rahman A, Teh LS, Griffiths B et al (2007) British Isles Lupus Assessment Group 2004 index is valid for assessment of disease activity in systemic lupus erythematosus. Arthritis Rheum 56:4113–4119

    Article  PubMed  PubMed Central  Google Scholar 

  9. Gladman DD, Ibañez D, Urowitz MB (2002) Systemic lupus erythematosus disease activity index 2000. J Rheumatol 29:288–291

    PubMed  Google Scholar 

  10. Jolly M, Kazmi N, Mikolaitis RA, Sequeira W, Block JA (2013) Validation of the Cutaneous Lupus Disease Area and Severity Index (CLASI) using physician- and patient-assessed health outcome measures. J Am Acad Dermatol 68:618–623

    Article  PubMed  Google Scholar 

  11. Furie RA, Petri MA, Wallace DJ, Ginzler EM, Merrill JT, Stohl W et al (2009) Novel evidence based systemic lupus erythematosus responder index. Arthritis Rheum 61:1143–1151

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  12. Thanou A, Chakravarty E, James JA, Merrill JT (2014) Which outcome measures in SLE clinical trials best reflect medical judgement? Lupus Sci Med 1:e000005

    Google Scholar 

  13. Furie R, Khamashta M, Merrill JT, Werth VP, Kalunian K, Brohawn P, et al (2017) CD1013 study investigators. Anifrolumab, an anti-interferon-a receptor monoclonal antibody, in moderate-to-severe systemic lupus erythematosus. Arthritis Rheumatol 69(2):376–386

    Google Scholar 

  14. Tanaka Y, Takeuchi T, Okada M, Nakajima H, Kawai S, Nagashim T et al (2020) Safety and tolerability of anifrolumab, a monoclonal antibody targeting type I interferon receptor, in Japanese patients with systemic lupus erythematosus: a multicentre, phase 2, open-label study. Mod Rheumatol 30(1):101–108

    Article  PubMed  CAS  Google Scholar 

  15. Merrill JT, Furie R, Werth VP, Khamashta M, Drappa J, Wang L, et al (2018) Anifrolumab effects on rash and arthritis: impact of the type I interferon gene signature in the phase IIb MUSE study in patients with systemic lupus erythematosus. Lupus Sci Med 5(1):e000284

    Google Scholar 

  16. Casey KA, Guo X, Smith MA, Wang S, Sinibaldi D, Sanjuan MA, et al (2018) Type I interferon receptor blockade with anifrolumab corrects innate and adaptive immune perturbations of SLE. Lupus Sci Med 5(1):e000286

    Google Scholar 

  17. Tummala R, Rouse T, Berglind A, Santiago L (2018) Safety, tolerability and pharmacokinetics of subcutaneous and intravenous anifrolumab in healthy volunteers. Lupus Sci Med 5(1):e000252

    Google Scholar 

  18. Bruce I, Nami A, Schwetje E, Pierson M, Chia Y, Kuruvilla D, et al (2019) PK/PD, safety and exploratory efficacy of subcutaneous anifrolumab in SLE: a phase-II study in interferon type I high patients with active skin disease [abstract]. Arthritis Rhematol 71(suppl 10). https://acrabstracts.org/abstract/pk-pd-safety-and-exploratory-efficacy-of-subcutaneous-anifrolumab-in-sle-a-phase-ii-study-in-interferon-type-i-high-patients-with-active-skin-disease/. Accessed March 21, 2020

    Google Scholar 

  19. Chatham W, Furie R, Saxena A, Brohawn P, Schwetje E, Abreu G, et al (2019) A phase 2, open-label extension study to evaluate long-term safety of anifrolumab in adults with systemic lupus erythematosus [abstract]. Arthritis Rheumatol 71(suppl 10). https://acrabstracts.org/abstract/a-phase-2-open-label-extension-study-to-evaluate-long-term-safety-of-anifrolumab-in-adults-with-systemic-lupus-erythematosus/. Accessed March 21, 2020

  20. Khamashta M, Merrill JT, Werth VP, Furie R, Kalunian K, Illei GG, et al (2016) CD1067 study investigators. Sifalimumab, an anti-interferon-a monoclonal antibody, in moderate to severe systemic lupus erythematosus: a randomised, double-blind, placebo-controlled study. Ann Rheum Dis 75:1909–1916

    Google Scholar 

  21. Takeuchi T, Tanaka Y, Matsumura R, Saito K, Yoshimura M, Amano K et al (2020) Safety and tolerability of sifalimumab, an anti-interferon-a monoclonal antibody, in Japanese patients with systemic lupus erythematosus: a multicentre, phase 2, open-label study. Mod Rheumatol 30(1):93–100

    Article  PubMed  CAS  Google Scholar 

  22. Petri M, Wallace D, Spindler A, Chindalore V, Kalunian K, Mysler E et al (2013) Sifalimumab, a human anti-interferon-a monoclonal antibody, in systemic lupus erythematosus: a phase 1 randomized, controlled, dose-escalation study. Arthritis Rheum 65:1011–1021

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  23. Merrill JT, Wallace D, Petri M, Kirou K, Yao Y, White W et al (2011) Safety profile and clinical activity of sifalimumab, a fully human anti-interferon a monoclonal antibody, in systemic lupus erythematosus: a phase 1, multicentre, double bind randomised study. Ann Rheum Dis 70:1905–1913

    Article  PubMed  CAS  Google Scholar 

  24. Yao Y, Richman L, Higgs BW, Morehouse CA, de los Reyes M, Brohawn P, et al (2009) Neutralization of interferon-alpha/beta-inducible genes and downstream effect in a phase 1 trial of anti-intereferon-alpha monoclonal antibody in systemic lupus erythematosus. Arthritis Rheum 60:1785–1796

    Google Scholar 

  25. Kalunian KC, Merrill JT, Maciuca R, McBride J, Townsend M, Wei X et al (2016) A phase II study of the efficacy and safety of rontalizumab (rhuMAb interferon-a) in patients with systemic lupus erythematosus (ROSE). Ann Rheum Dis 75:196–202

    Article  PubMed  Google Scholar 

  26. McBride JM, Jiang J, Abbas A, Morimoto A, Li J, Maciuca R et al (2012) Safety and pharmacodynamics of rontalizumab in patients with systemic lupus erythematosus: results of a phase 1, placebo-controlled, double-blind, dose-escalation study. Arthritis Rheum 64:3666–3676

    Article  PubMed  CAS  Google Scholar 

  27. Tcherepanova M, Curtis M, Sale M, Miesowicz F, Nicolette C (2012) Results of a randomized placebo controlled phase Ia study of AGS-009, a humanized anti-interferon-alpha monoclonal antibody in subjects with systemic lupus erythematosus. Ann Rheum Dis 71(suppl 3):536–537

    Google Scholar 

  28. Morehouse C, Chang L, Wang L, Brohawn P, Ueda S, Ilei G, et al. Target modulation of a type I interferon (IFN) gene signature with sifalimumab or anifrolumab in systemic lupus erythematosus (SLE) patients in two open label phase 2 Japanese trials. In: Paper Presented at: 2014 American College of Rheumatology Annual Meeting, Boston, USA [abstract 719]. Available from http://acrabstracts.org/abstract/target-modulation-of-a-type-i-interferon-ifn-gene-signature-with-sifalimumab-or-anifrolumab-in-systemic-lupus-erythematosus-sle-patients-in-two-open-label-phase-2-japanese-trials/. Accessed 22 March, 2020

  29. Lauwerys BR, Hachulla E, Spertini F, Lazaro E, Jorgensen C, Mariette X et al (2013) Down-regulation of interferon signature in systemic lupus erythematosus patients by active immunization with interferon a-kinoid. Arthritis Rheum 65:447–456

    Article  PubMed  CAS  Google Scholar 

  30. Houssiau FA, Thanou A, Mazur M, Ramiterre E, Gomez Mora DA, Misterska-Skora, et al (2020) IFN-a kinoid in systemic lupus erythematosus: results from a phase IIb, randomised, placebo-controlled study. Ann Rheum Dis 79(3):347–355

    Google Scholar 

  31. Mathian A, Amoura Z, Adam E, Colaone F, Hoekman M, Dhellin O et al (2011) Active immunisation of human interferon a transgenic mice with a human interferon a kinoid induces antibodies that neutralise interferon a in sera from patients with systemic lupus erythematosus. Ann Rheum Dis 70:1138–1143

    Article  PubMed  CAS  Google Scholar 

  32. Morimoto AM, Flesher DT, Yang J, Wolslegel K, Wang X, Brady A et al (2011) Association of endogeneous anti-interferon-a autoantibodies with decreased interferon-pathway and disease activity in patients with systemic lupus erythematosus. Arthritis Rheum 63:2407–2415

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  33. Zagury D, Buanec H, Mathian A, Larcier P, Burnett R, Amoura Z et al (2009). IFNa kinoid vaccine-induced neutralizing antibodies prevent clinical manifestations in a lupus flare murine mode. Proc Natl Acad Sci USA 106: 5249–5294

    Google Scholar 

  34. Ducreaux J, Houssiau FA, Vandepapeliere P, Jorgensen C, Lazaro E, Spertini F et al (2016) Interferon a kinoid induces neutralizing anti-interferon a antibodies that decrease the expression of interferon-induced and B cell activation associated transcripts: analysis of extended follow-up data from the interferon a kinoid phase I/II study. Rheumatology (Oxford) 55(10):1901–1905

    Article  CAS  Google Scholar 

  35. Franklyn K, Lau CS, Navarra SV, Louthrenoo W, Lateef A, Hamijoyo L et al (2016) Definition and initial validation of a Lupus Low Disease Activity State (LLDAS). Ann Rheum Dis 75:1615–1621

    Article  PubMed  CAS  Google Scholar 

  36. Petri M, Kim MY, Kalunian KC, Grossman J, Hahn BH, Sammaritano LR, et al. for the OCSELENA Trial (2005) Combined oral contraceptives in women with systemic lupus erythematosus. NEJM 353:2550–2558

    Google Scholar 

  37. Welcher AA, Boedigheimer M, Kivitz AJ, Amoura Z, Buyon J, Rudinskaya A et al (2015) Blockade of interferon-gamma normalizes interferon-regulated gene expression and serum CXCL10 levels in patients with systemic lupus erythematosus. Arthritis Rheumatol 67:2713–2722

    Article  PubMed  PubMed Central  Google Scholar 

  38. Graninger WB, Hassfeld W, Pesau BB, Machold KP, Zielinski CC, Smolen JS (1991) Induction of systemic lupus erythematosus by intereferon gamma in a patient with rheumatoid arthritis. J Rheumatol 18:1621–1622

    PubMed  CAS  Google Scholar 

  39. Robak E, Smolewski P, Wozniacka A, Sysa-Jedrzejowska A, Stepien H, Robak T (2004) Relationship between peripheral blood dendritic cells and cytokines involved in the pathogenesis of systemic lupus erythematosus. Eur Cytokine Networks 15:222–230

    CAS  Google Scholar 

  40. Rana A, Minz RW, Aggarwal R, Anand S, Pasricha N, Singh S (2012) Gene expression of cytokines (TNF-alpha, IFN-gamma), serum profiles of IL-17 and IL-23 in paediatric systemic lupus erythematosus. Lupus 21:1105–1112

    Article  PubMed  CAS  Google Scholar 

  41. Csiszar A, Nagy G, Gergely P, Pozsonyi T, Pocski E (2000) Increased interferon-gamma (IFN-gamma), IL-10 and decreased IL-4 mRNA expression in peripheral blood mononuclear cells (PBMC) from patients with systemic lupus erythematosus (SLE). Clin Exp Immunol 122:464–470

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  42. Hervier B, Beziat V, Haroche J, Mathian A, Lebon P, Ghillani-Dalbin P et al (2011) Phenotype and function of natural killer cells in systemic lupus erythematosus: excess interferon-gamma production in patients with active disease. Arthritis Rheum 63:1698–1706

    Article  PubMed  CAS  Google Scholar 

  43. Lemay S, Mao C, Singh AK (1996) Cytokine gene expression in the MRL/lpr model of lupus nephritis. Kidney Int 50:85–93

    Article  PubMed  CAS  Google Scholar 

  44. Enghard P, Langnickel D, Riemekasten G (2006) T cell cytokine imbalance towards production of IFN-gamma and IL-10 in NZB/W F1 lupus-prone mice is associated with autoantibody levels and nephritis. Scand J Rheumatol 35:209–216

    Article  PubMed  CAS  Google Scholar 

  45. Jacob CO, van der Meide PH, McDeviitt HO (1987) In vivo treatment of (NZB X NZW)F1 lupus-like nephritis with monoclonal antibody to gamma interferon. J Exp Med 166:798–803

    Article  PubMed  CAS  Google Scholar 

  46. Schmidt T, Paust HJ, Krebs CF, Turner JE, Kaffke A, Bennstein SB et al (2015) Function of the Th17/interleukin-17A immune response in murine lupus nephritis. Arthritis Rheumatol 67:475–487

    Article  PubMed  CAS  Google Scholar 

  47. Haas C, Ryffel B, Le Hir M (1998) IFN-gamma receptor deletion prevents autoantibody production and glomerulonephritis in lupus-prone (NZB x NZW)F1 mice. J Immunol 160:3713–3718

    PubMed  CAS  Google Scholar 

  48. Werth VP, Fiorentino D, Sullivan BA, Boedigheimer MJ, Chiu K et al (2017) Brief report: Pharmacodynamics, safety and clinical efficacy of AMG 811, a human anti-intereferon-y antibody, in patients with discoid lupus erythematosus. Arthritis Rheumatol 69(5):1028–1034

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  49. Boedigheimer M, Martin D, Amoura Z, Sánchez-Guerrero J, Romero-Diaz J, Kivitz A et al (2017) Safety, pharmacokinetics and pharmacodynamics of AMG 811, an anti-interferon-γ monoclonal antibody, in SLE subjects without or with lupus nephritis. Lupus Sci Med 4:3000226

    Article  Google Scholar 

  50. Van Vollenhoven RF, Hahn BH, Tsokos GC, Wagner CL, Lipsky P, Touma Z et al (2018) Efficacy and safety of ustekinumab, an IL-12 and IL-23 inhibitor, in patients with active systemic lupus erythematosus: results of a multicentre, double-blind, phase 2, randomised, controlled study. Lancet 392:1330–1339

    Article  PubMed  Google Scholar 

  51. Cesaroni M, Seridi L, Jordan J, Sweet, K, Keying MA, Franks C, et al (2019) Biomarker profiling reveals novel mechanistic insights into ustekinumab therapeutic responses in systemic lupus erythematosus [abstract]. Arthritis Rheumatol 71(suppl 10). https://acrabstracts.org/abstract/biomarker-profiling-reveals-novel-mechanistic-insights-into-ustekinumab-therapeutic-responses-in-systemic-lupus-erythematosus/. Accessed April 5, 2020

  52. Chyuan IT, Tzeng HT, Chen JY (2019) Signaling pathways of type I and type III interferons and targeted therapies in systemic lupus erythematosus. Cells 8:E963

    Article  PubMed  CAS  Google Scholar 

  53. Jewell NA, Cline T, Mertz SE, Smirnov SV, Flaño E, Schindler C et al (2010) Lambda interferon is the predominant interferon induced by influenza A virus infection in vivo. J Virol 84:11515–11522

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  54. Amezcua-Guerra LM, Ferrusquía-Toriz D, Castillo-Martinez D, Márquez-Velasco R, Chávez-Rueda AK, Bojalil R (2015) Limited effectiveness for the therapeutic blockade of interferon alpha in systemic lupus erythematosus: a possible role for type III interferons. Rheumatology (Oxford) 54:203–205

    Article  CAS  Google Scholar 

  55. Wang Y, Li T, Chen Y, Wei H, Sun R, Tian Z (2017) Involvement of NK cells in IL-28B-mediated immunity against influenza virus infection. J Immunol 199:1012–1020

    Article  PubMed  CAS  Google Scholar 

  56. Megjugorac NJ, Gallagher GE, Gallagher G (2009) Modulation of human plasmacytoid DC function by IFN-lambda1 (IL-29). J Leukocyte Biol 86:1359–1363

    Article  PubMed  CAS  Google Scholar 

  57. Koltsida O, Hausding M, Stavropoulos A, Koch S, Tzelepis G, Ubel C et al (2011) IL-28A (IFN-lambda2) modulates lung DC function to promote Th1 immune skewing and suppress allergic airway disease. EMBO Mol Med 3:348–361

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  58. Hagberg N, Rönnblom L (2015) Systemic lupus erythematosus - a disease with a dysregulated type I interferon system. Scand J Immunol 82:199–207

    Article  PubMed  CAS  Google Scholar 

  59. Wu Q, Yang Q, Lourenco E, Sun H, Zhang Y (2011) Interferon-lambda1 induces peripheral blood mononuclear cell-derived chemokines secretion in patients with systemic lupus erythematosus: its correlation with disease activity. Arthritis Res Ther 13:R88

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  60. Zahn S, Rehkämper C, Kümmerer BM, Ferring-Schmidt S, Bieber T, Tüting T et al (2011) Evidence for a pathophysiological role of keratinocyte-derived type III interferon (IFNλ) in cutaneous lupus erythematosus. J Invest Dermatol 131:133–140

    Article  PubMed  CAS  Google Scholar 

  61. Zickert A, Oke V, Parodis I, Svenungsson E, Sundström Y, Gunnarsson I (2016) Interferon (IFN-λ) is a potential mediator in lupus nephritis. Lupus Sci Med 3:e000170

    Google Scholar 

  62. Oon S, Huynh H, Tai TY, Ng M, Monaghan K, Biondo M, et al (2016) A cytotoxic anti-IL-3Ra antibody targets key cells and cytokines implicated in systemic lupus erythematosus. JCI Insight 1(6):e86131

    Google Scholar 

  63. Lauterbach H, Bathke B, Gilles S, Traidl-Hoffmann C, Luber CA, Fejer G et al (2010) Mouse CD8alpha+ DCs and human BDCA3+ DCs are major producers of IFN-lambda in response to poly IC. J Exp Med 207:2703–2717

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  64. Ank N, West H, Bartholdy C, Eriksson K, Thomsen AR, Paludan SR (2006) Lambda interferon (IFN-lambda), a type III IFN, is induced by viruses and IFNs and displays potent antiviral activity against select virus infections in vivo. J Virol 80:4501–4509

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  65. Liu YJ (2005) IPC: professional type 1 interferon-producing cells and plasmacytoid dendritic cells precursors. Annu Rev Immunol 23:275–306

    Article  PubMed  CAS  Google Scholar 

  66. Banchereau J, Pascual V (2006) Type I interferon in systemic lupus erythematosus and other autoimmune diseases. Immunity 25(3):383–392

    Article  PubMed  CAS  Google Scholar 

  67. Means TK, Latz E, Hayashi F, Murali MR, Golenbock ET, Luster AD (2005) Human lupus autoantibody-DNA complexes activate DCs through cooperation of CD32 and TLR9. J Clin Invest 115:407–417

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  68. Lande R, Ganguly D, Facchinetti V, Frasca L, Conrad C, Gregorio J, et al (2011) Neutrophils activate plasmacytoid dendritic cells by releasing self-DNA-peptide complexes in systemic lupus erythematosus. Sci Transl Med 3:73ra19

    Google Scholar 

  69. Fiore N, Castellano G, Blasi A, Capobianco C, Loverre A, Montinaro V et al (2008) Immature myeloid and plasmacytoid dendritic cells infiltrate renal tubulointerstitium in patients with lupus nephritis. Mol Immunol 45:259–265

    Article  PubMed  CAS  Google Scholar 

  70. Tucci M, Quatraro C, Lomabardi L, Pelligrino C, Dammacco F, Silvestris F (2008) Glomerular accumulation of plasmacytoid dendritic cells in active lupus nephritis: role of interleukin-18. Arthritis Rheum 58:251–262

    Article  PubMed  CAS  Google Scholar 

  71. Migita K, Miyashita T, Maeda Y, Kimura H, Nakamura M, Yatsuhashi H et al (2005) Reduced blood BDCA2+ (lymphoid) and CD11c+ (myeloid) dendritic cells in systemic lupus erythematosus. Clin Exp Immunol 142:84–91

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  72. Cederblad B, Blomberg S, Vallin H, Perers A, Alm GV, Rönnblom L (1998) Paitents with systemic lupus erythematosus have reduced numbers of circulating natural interferon-a producing cells. J Autoimmun 11:465–470

    Article  PubMed  CAS  Google Scholar 

  73. Henriques A, Inês L, Carvalheiro T, Couto M, Andrade A, Pedreiro S et al (2012) Functional characterization of peripheral blood dendritic cells and monocytes in systemic lupus erythematosus. Rheumatol Int 32:863–869

    Article  PubMed  CAS  Google Scholar 

  74. Kwok SK, Lee JY, Park SH, Cho ML, Min SY, Park SH et al (2008) Dysfunctional interferon-alpha production by peripheral plasmacytoid dendritic cells upon Toll-like receptor-9 stimulation in patients with systemic lupus erythematosus. Arthritis Res Ther 10:R29

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  75. Jin O, Kavikondala S, Sun L, Fu RMok MY, Chan A, et al (2008) Systemic lupus erythematosus patients have increased number of circulating plasmacytoid dendritic cells, but decreased myeloid dendritic cells with deficient CD83 expression. Lupus 17:654–662

    Article  PubMed  CAS  Google Scholar 

  76. Farkas L, Beiske K, Lund-Johansen F, Brandtzaeg P, Jahsen F (2001) Plasmacytoid dendritic cells (natural interferon-a/b-producing cells) accumulate in cutaneous lupus erythematosus lesions. Am J Pathol 159:237–243

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  77. Blomberg S, Eloranta ML, Cederblad B, Nordlind K, Alm GV, Rönnblom L (2001) Presence of cutaneous interferon-alpha producing cells in patients with systemic lupus erythematosus. Lupus 10:484–490

    Article  PubMed  CAS  Google Scholar 

  78. Miyashita A, Fukushima S, Makino T, Yoshino Y, Yamashita J, Honda N et al (2014) Proportion of lymphocytic inflammation with CD123 positive cells in lupus erythematosus profundus predict a clinical response to treatment. Acta Derm Venereol 94:563–567

    Article  PubMed  CAS  Google Scholar 

  79. Jin O, Kavikondala S, Mok MY, Sun L, Gu J, Fu R et al (2010) Abnormalities in circulating plasmacytoid dendritic cells in patients with systemic lupus erythematosus. Arthritis Res Ther 12:R137

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  80. Morel L (2010) Genetics of SLE: evidence from mouse models. Nat Rev Rheumatol 6:348–357

    Article  PubMed  Google Scholar 

  81. Sisirak V, Ganguly D, Lewis KL, Couillault C, Tanaka L, Bolland S, et al (2014) Genetic evidence for the role of plasmacytoid dendritic cells in systemic lupus erythematosus. J Exp Med 1969–1976

    Google Scholar 

  82. Rowland SL, Riggs JM, Gilfillan S, Bugatti M, Vermi W, Kolbeck R et al (2014) Early, transient depletion of plasmacytoid dendritic cells ameliorates autoimmunity in a lupus model. J Exp Med 211:1977–1991

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  83. Davison LM, Jorgensen TN (2015) Sialic acid-binding immunoglobulin-type lectin H-positive plasmacytoid dendritic cells drive spontaneous lupus-like disease development in B6.Nba2 mice. Arthritis Rheumatol 67:1012–1022

    Google Scholar 

  84. Pellerin A, Otero K, Czerkowicz JM, Kerns HM, Shapiro RI, Ranger AM et al (2015) Anti-BDCA2 monoclonal antibody inhibits plasmacytoid dendritic cell activation through Fc-dependent and Fc-independent mechanisms. EMBO Mol Med 7:464–476

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  85. Furie R, Werth VP, Merola JF, Stevenson L, Reynolds TL, Naik H et al (2019) Monoclonal antibody targeting BDCA2 ameliorates skin lesions in systemic lupus erythematosus. J Clin Invest 129:1359–1371

    Article  PubMed  PubMed Central  Google Scholar 

  86. Furie R, van Vollenhoven R, Kalunian K, Navarra S, Romero-Díaz J, Werth V, et al (2020) Efficacy and safety results from a phase 2, randomized, double-blind trial of BIIB059, an anti-blood dendritic cell antigen 2 antibody, in SLE [abstract]. Arthritis Rheumatol 72(suppl 10). http://acrabstracts.org/abstract/efficacy-and-safety-results-from-a-phase-2-randomized-double-blind-trial-of-biib059-an-anti-blood-dendritic-cell-antigen-2-antibody-in-sle/. Accessed April 11, 2021

  87. Werth V, Furie R, Romero-Diaz J, Navarra S, Kalunian K, van Vollenhoven R, et al, and LILAC investigators (2020) OPO193 BIIB059, a humanized monoclonal antibody targeting BDCA2 on plasmacytoid dendritic cells (pDC), shows dose-related efficacy in the phase 2 LILAC study in patients (pts) with active cutaneous lupus erythematosus (LCE). Ann Rheum Dis 79:120–121

    Google Scholar 

  88. Henriquez JE, Crawford RB, Kaminski NE (2019) Suppression of CpG-ODN-mediated IFNa and TNFa response in human plasmacytoid dendritic cells (pDC) by cannabinoid receptor 2 (CB2)-specific agonists. Toxicol Appl Pharmacol 369:82–89

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  89. Dillmann C, Ringel C, Ringleb J, Mora J, Olesch C, Fink AF et al (2016) S1PR4 signaling attenuates ILT 7 internalization to limit IFN-a production by human plasmacytoid dendritic cells. J Immunol 196:1579–1590

    Article  PubMed  CAS  Google Scholar 

  90. Bardwell PD, Gu J, McCarthy D, Wallace C, Bryant S, Goess C et al (2009) The Bcl-2 family antagonist ABT-737 significantly inhibits multiple animal models of autoimmunity. J Immunol 182:7482–7489

    Article  PubMed  CAS  Google Scholar 

  91. Zhan Y, Carrington EM, Ko HJ, Vikstrom IB, Oon S, Zhang JG et al (2015) Bcl-2 antagonists kill plasmacytoid dendritic cells from lupus-prone mice and dampen interferon-a production. Arthritis Rheumatol 67:797–808

    Article  PubMed  CAS  Google Scholar 

  92. Hirai M, Kadowaki N, Kitawaki T, Fujita H, Takaori-Kondo A, Fukui R et al (2011) Bortezomib suppresses function and survival of plasmacytoid dendritic cells by targeting intracellular trafficking of Toll-like receptors and endoplasmic reticulum homeostasis. Blood 117(2):500–509

    Article  PubMed  CAS  Google Scholar 

  93. Ji J, Fan H, Li F, Li X, Dong G, Gong W et al (2015) A benzenediamine derivative fc-99 attenuates lupus-like syndrome in MRL/lpr mice related to suppression of pDC activation. Immunol Lett 168:355–365

    Article  PubMed  CAS  Google Scholar 

  94. Ishii T, Tanaka Y, Kawakami A, Saito K, Ichinose K, Fujii H et al (2018) Multicenter double-blind randomized controlled trial to evaluate the effectiveness and safety of bortezomib as a treatment for refractory systemic lupus erythematosus. Mod Rheumatol 28:982–992

    Article  CAS  Google Scholar 

  95. Segarra A, Arredondo KV, Jaramillo J, Jatem E, Salcedo MT, Agraz I et al (2020) Efficacy and safety of bortezomib in refractory lupus nephritis: a single centre experience. Lupus 29:118–125

    Article  PubMed  CAS  Google Scholar 

  96. Alexander T, Sarfert R, Klotsche J, Kühl AA, Rubbert-Roth A, Lorenz HM et al (2015) The proteasome inhibitor bortezomib depletes plasma cells and ameliorates clinical manifestations of refractory systemic lupus erythematosus. Ann Rheum Dis 74:1474–1478

    Article  PubMed  CAS  Google Scholar 

  97. Lu P, Fleischmann R, Curtis C, Ignatenko S, Clarke SH, Desai M et al (2018) Safety and pharmacodynamics of venetoclax (ABT-199) in a randomized single and multiple ascending dose study in women with systemic lupus erythematosus. Lupus 27:290–302

    Article  PubMed  CAS  Google Scholar 

  98. Macanovic M, Sinicropi D, Shak S, Baughman S, Thiru S, Lachmann PJ (1996) The treatment of systemic lupus erythematosus (SLE) in NZB/W F1 hybrid mice; studies with recombinant murine DNase and with dexamethasone. Clin Exp Immunol 106:243–252

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  99. Davis JC Jr, Manzi S, Yarboro C, Rairie J, McInnes I, Averthelyi D et al (1999) Recombinant human Dnase I (rhDNase) in patients with lupus nephritis. Lupus 8:68–76

    Article  PubMed  Google Scholar 

  100. Sun X, Widerman A, Agrawal N, Teal T, Tanaka L, Hudkins K et al (2013) Increased RNase expression reduces inflammation and prolongs survival in TLR7 transgenic mice. J Immunol 190:2536–2543

    Article  PubMed  CAS  Google Scholar 

  101. Burge DJ, Eisenman J, Byrnes-Blake K, Smolak P, Lau K, Cohen SB et al (2017) Safety, pharmacokinetics, and pharmacodynamics of RSLV-132, an RNase-Fc fusion protein in systemic lupus erythematosus: a randomized, double-blind, placebo-controlled study. Lupus 26:825–834

    Article  PubMed  CAS  Google Scholar 

  102. Resolve therapeutics. RSLV-132 demonstrates clinically meaningful improvement in patients with systemic lupus erythematosus in phase 2a clinical trial. December 9 2020. Available at https://www.prnewswire.com/news-releases/rslv-132-demonstrates-clinically-meaningful-improvement-in-patients-with-systemic-lupus-erythematosus-in-phase-2a-clinical-trial-301189541.html. Accessed 11 April, 2021

  103. Tillmanns S, Kolligs C, D’Cruz D, Doria A, Hachulla E, Voll R, et al. SM101, a novel recombinant, soluble, human FcyIIb receptor, in the treatment of systemic lupus erythematosus: results of a double-blind, placebo-controlled multicentre study. In: Paper Presented at: 2014 American College of Rheumatology Annual Meeting, Boston, USA [abstract 2833]. Available from https://acrabstracts.org/abstract/sm101-a-novel-recombinant-soluble-human-fcγiib-receptor-in-the-treatment-of-systemic-lupus-erythematosus-results-of-a-double-blind-placebo-controlled-multicenter-study/. Accessed 12 April 2020

    Google Scholar 

  104. Kono DH, Haraldsson MK, Lawson BR, Pollard KM, Koh YT, Du X et al (2009) Endosomal TLR signaling is required for anti-nucleic acid and rheumatoid factor autoantibodies in lupus. Proc Natl Acad Sci USA 106:12061–12066

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  105. Christensen SR, Shupe J, Nickerson K, Kashgarian M, Flavell RA, Schlomchik MJ (2006) Toll-like receptor 7 and TLR9 dictate autoantibody specificity and have opposing inflammatory and regulatory roles in a murine model of lupus. Immunity 25:417–428

    Article  PubMed  CAS  Google Scholar 

  106. Savarese E, Steinberg C, Pawar RD, Reindl W, Akira S, Anders HJ et al (2008) Requirement of Toll-like receptor 7 for pristane-induced production of autoantibodies and development of murine lupus nephritis. Arthritis Rheum 58:1107–1115

    Article  PubMed  CAS  Google Scholar 

  107. Savarese E, Chae OW, Trowitzsch S, Weber G, Kastner B, Akira S et al (2006) U1 small nuclear ribonucleoprotein immune complexes induce type I interferon in plasmacytoid dendritic cells through TLR7. Blood 107:3229–3234

    Article  PubMed  CAS  Google Scholar 

  108. Boulé MW, Broughton C, Mackay F, Akira S, Marshak-Rothstein A, Rifkin IR (2004) Toll-like receptor 9-dependent and -independent dendritic cell activation by chromatin-immunoglobulin G complexes. J Exp Med 199:1631–1640

    Article  PubMed  PubMed Central  Google Scholar 

  109. Zorro S, Arias M, Riaño F, Paris S, Ramírez LA, Uribe O et al (2009) Response to ODN-CpG by B cells from patients with systemic lupus erythematosus correlates with disease activity. Lupus 18:718–726

    Article  PubMed  CAS  Google Scholar 

  110. Umiker BR, Andersson S, Fernandez L, Korgaokar P, Larbi A, Pilichowska M et al (2014) Dosage of X-linked toll-like receptor 8 determines gender differences in the development of systemic lupus erythematosus. Eur J Immunol 44:1503–1516

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  111. Tran NL, Manzin-Lorenzi C, Santiago-Raber ML (2015) Toll-like receptor 8 deletion accelerates autoimmunity in a mouse model of lupus through a Toll-like receptor 7-dependent mechanism. Immunology 145:60–70

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  112. The Canadian Hydroxychloroquine Study Group (1991). A randomized study of the effect of withdrawing hydroxychloroquine sulfate in systemic lupus erythematosus. N Engl J Med 324:150–154

    Google Scholar 

  113. Alarcón GS, McGwin G Jr, Bertoli AM, Fessler BJ, Calvo-Alén J, Bastian HM et al (2007) Effect of hydroxychloroquine on the survival of patients with systemic lupus erythematosus: data from LUMINA, a multiethnic US cohort (LUMINA L). Ann Rheum Dis 66:1168–1172

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  114. Cairoli E, Rebella M, Danese N, Garra V, Borba EF (2012) Hydroxychloroquine reduces low-density lipoprotein cholesterol levels in systemic lupus erythematosus: a longitudinal evaluation of the lipid-lowering effect. Lupus 21:1178–1182

    Article  PubMed  CAS  Google Scholar 

  115. Espinola RG, Pierangeli SS, Gharavi AE, Harris EN (2002) Hydroxychloroquine reverses platelet activation induced by human IgG antiphospholipid antibodies. Thromb Haemost 87:518–522

    Article  PubMed  CAS  Google Scholar 

  116. Wu YW, Tang W, Zuo JP (2015) Toll-like receptors: potential targets for lupus treatment. Acta Pharmacol Sin 36:1395–1407

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  117. Gardet A, Pellerin A, McCarl CA, Diwanji R, Wang W, Donaldson D et al (2019) Effect of in vivo hydroxychloroquine and ex vivo anti-BDCA2 mAb treatment on pDC IFNa production from patients affected with cutaneous lupus erythematosus. Front Immunol 10:275

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  118. Sacre K, Criswell LA, McCune JM (2012) Hydroxychloroquine is associated with impaired interferon-alpha and tumor necrosis factor-alpha production by plasmacytoid dendritic cells in systemic lupus erythematosus. Arthritis Res Ther 14:R155

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  119. Barrat FJ, Meeker T, Chan JH, Guiducci C, Coffman RL (2007) Treatment of lupus-prone mice with a dual inhibitor of TLR7 and TLR9 leads to reduction of autoantibody production and amelioration of disease symptoms. Eur J Immunol 37:3582–3586

    Article  PubMed  CAS  Google Scholar 

  120. Barrat FJ, Meeker T, Gregorio J, Chan JH, Uematsu S, Akira S et al (2005) Nucleic acids of mammalian origin can act as endogenous ligands for Toll-like receptors and may promote systemic lupus erythematosus. J Exp Med 202:113–119

    Article  CAS  Google Scholar 

  121. Dynavax (DVAX) reports DV1179 did not meet endpoints in phase 1b/2a. August 7 2014. Available at https://www.streetinsider.com/Corporate+News/Dynavax+%28DVAX%29+Reports+DV1179+Did+Not+Meet+Endpoints+in+Phase+1b2a/9729788.html. Accessed 13 April, 2020

  122. Kimball AB, Krueger J, Sullivan T, Arbeit RD. IMO-3100, an antagonist of Toll-like receptor (TLR) 7 and TLR9, demonstrates clinical activity in psoriasis patients with 4 weeks of treatment in a phase 2a trial. Available at https://www.iderapharma.com/wp-content/uploads/2015/11/iid_2013_presentation_final.pdf. Accessed 13 April, 2020

  123. Balak DM, van Doorn MB, Arbeit RD, Rijneveld R, Klaasen E, Sullivan T et al (2017) IMO-8400, a toll-like receptor 7, 8, and 9 antagonist, demonstrates clinical activity in a phase 2a, randomized, placebo-controlled trial in patients with moderate-to-severe plaque psoriasis. Clin Immunol 174:63–72

    Article  PubMed  CAS  Google Scholar 

  124. Zhu F, Yu D, Kandimalla E, La Monica N, Agrawal S. Treatment with IMO-3100, a novel TLR7 and TLR9 dual antagonist, inhibits disease development in lupus prone NZBW/F1 mice. Keystone Symposia: Dendritic Cells and the Initiation of Adaptive Immunity; Santa Fe 2011

    Google Scholar 

  125. Zhu F, Jiang W, Dong Y, Kandimalla E, La Monica N, Agrawal S (2012) IMO-8400, a novel TLR7, TLR8 and TLR9 antagonist, inhibits disease development in lupus-prone NZBW/F1 mice. J Immunol 188:119.12

    Google Scholar 

  126. Capolunghi F, Rosado MM, Cascioli S, Girolami E, Bordasco S, Vivarelli M et al (2010) Pharmacological inhibition of TLR9 activation blocks autoantibody production in human B cells from SLE patients. Rheumatology (Oxford) 49:2281–2289

    Article  CAS  Google Scholar 

  127. Loiarro M, Capolunghi F, Fantò N, Gallo G, Campo S, Arseni B et al (2007) Pivotal advance: inhibition of MyD88 dimerization and recruitment of IRAK1 and IRAK4 by a novel peptidomimetic compound. J Leukoc Biol 82:801–810

    Article  PubMed  CAS  Google Scholar 

  128. Lipford G, Forsbach A, Zepp C, Nguyen T, Weeratna R, McCluskie M, et al. Selective toll-like receptor 7/8/9 antagonists for the oral treatment of autoimmune diseases. In: Paper Presented at: 2007 American College of Rheumatology Annual Meeting, Boston, USA [abstract 1596]. Available from https://acr.confex.com/acr/2007/webprogram/Paper8044.html. Accessed 13 April, 2020

  129. AdisInsight, CpG 52364. 2010. Available at https://adisinsight.springer.com/drugs/800027264. Accessed 13 April, 2020

  130. Mok CC (2019) The Jakinibs in systemic lupus erythematosus: progress and prospects. Expert Opin Investig Drugs 28:85–92

    Article  PubMed  CAS  Google Scholar 

  131. Markopoulou A, Kyttaris VC (2013) Small molecules in the treatment of systemic lupus erythematosus. Clin Immunol 148:359–368

    Article  PubMed  CAS  Google Scholar 

  132. Montealegre Sanchez GA, Reinhardt AL, Brogan P, Berkun Y, Brown D, Chira P et al (2013) Chronic atypical neutrophilic dermatosis with lipodystrophy and elevated temperatures (CANDLE): clinical characterization and initial response to Janus Kinase inhibition with baricitinib [abstract]. Arthritis Rheum 65(Suppl 10):1782

    Google Scholar 

  133. Liu Y, Jesus AA, Marrero B, Yang D, Ramsey SE, Montealegre Sanchez GA, Tenbrock K et al (2014) Activated STING in a vascular and pulmonary syndrome. NEJM 371:507–518

    Article  PubMed  CAS  Google Scholar 

  134. Wallace D, Furie R, Tanaka Y, Kalunian K, Mosca M, Petri M et al (2018) Baricitinib for systemic lupus erythematosus: a double-blind, randomised, placebo-controlled, phase 2 trial. Lancet 392:222–231

    Article  CAS  PubMed  Google Scholar 

  135. Keown A. Gilead and Galapagos’ JAK inhibitor stumbles in mid-stage lupus trial. Available at https://www.biospace.com/article/gilead-and-galapagos-filgotinib-fails-in-mid-stage-lupus-trial/. Accessed April 19, 2020

  136. Han P, Pohlmeyer C, Shang C, Cui Z, Lopez D, Clarke A, et al (2018) Monotherapy with filgotinib, a JAK1-selective inhibitor, reduces disease severity and alters immune cell subsets in the NZB/W F1 murine model of lupus [abstract]. Arthritis Rheumatol 70(suppl 10). https://acrabstracts.org/abstract/monotherapy-with-filgotinib-a-jak1-selective-inhibitor-reduces-disease-severity-and-alters-immune-cell-subsets-in-the-nzb-w-f1-murine-model-of-lupus/. Accessed April 19, 2020

  137. van Vollenhoven RF, Layton M, Kahl L, Schifano L, Hachulla E, Machado D et al (2015) DRESS syndrome and reversible liver function abnormalities in patients with systemic lupus erythematosus treated with the highly selective JAK-1 inhibitor GSK2586184. Lupus 24:648–649

    Article  PubMed  Google Scholar 

  138. Presto JK, Okon LG, Feng R, Wallace DJ, Furie R, Fiorentino D et al (2018) Computerized planimetry to assess clinical responsiveness in a phase II randomized trial of topical R333 for discoid lupus erythematosus. Br J Derm 178:1308–1314

    Article  CAS  Google Scholar 

  139. Hasni S, Gupta S, Davis M, Poncio E, Temesgen-Oyelakin Y, Biehl A, et al (2019). A phase 1B/2A trial of tofacitinib, an oral janus kinase inhibitor, in systemic lupus erythematosus. [abstract]. Lupus Sci Med. https://doi.org/10.1136/lupus-2019-lsm.183. Accessed April 19, 2020

  140. Sarhan RA, Aboelenein HR, Sourour SK, Fawzy IO, Salah S, Abdelaziz AI (2015) Targeting E2F1 and c-Myc expression by microRNA-17-5p represses interferon-stimulated gene MxA in peripheral blood mononuclear cells of pediatric systemic lupus erythematosus patients. Discov Med 19:419–425

    PubMed  Google Scholar 

  141. Han X, Wang Y, Zhang X, Qin Y, Qu B, Wu L et al (2016) MicroRNA-130b ameliorates murine lupus nephritis through targeting the type 1 interferon pathway on renal mesangial cells. Arthritis Rheumatol 68:2232–2243

    Article  PubMed  CAS  Google Scholar 

  142. Fabricius D, Neubauer M, Mandel B, Schütz C, Viardot A, Vollmer A et al (2010) Prostagladin E2 inhibits IFN-alpha secretion and Th1 costimulation by human plasmacytoid dendritic cells via E-prostanoid 2 and E-prostainoid 4 receptor engagement. J Immunol 184:677–684

    Article  PubMed  CAS  Google Scholar 

  143. Khoryati L, Augusto JF, Contin-Bordes C, Douchet I, Mitrovic S, Truchetet ME, et al (2016) Federation Hospitalo-Universitaire ACRONIM. IgE inhibits Toll-like receptor 7- and toll-like receptor-9-mediated expression of interferon-a by plasmacytoid dendritic cells in patients with systemic lupus erythematosus. Arthritis Rheumatol 68:2221–2231

    Google Scholar 

  144. Mina-Osorio P, LaStant J, Keirstead N, Whittard T, Ayala J, Stefanova S et al (2013) Suppression of glomerulonephritis in lupus-prone NZB x NZW mice by RN486, a selective inhibitor of Bruton’s tyrosine kinase. Arthritis Rheum 65:2380–2391

    Article  PubMed  CAS  Google Scholar 

  145. Bender AT, Pereira A, Fu K, Samy E, Wu Y, Liu-Bujalski L et al (2016) Btk inhibition treats TLR7/IFN driven murine lupus. Clin Immunol 164:65–77

    Article  PubMed  CAS  Google Scholar 

  146. Katewa A, Wang Y, Hackney JA, Huang T, Suto E, Ramamoorthi N, et al (2017) Btk-specific inhibition blocks pathogenic plasma cell signatures and myeloid cell-associated damage in IFNa-driven lupus nephritis. JCI Insight 2(7):e90111

    Google Scholar 

  147. Wu L, Qin Y, Xia S, Dai M, Han X, Wu Y et al (2016) Identification of cyclin-dependent kinase 1 as a novel regulator of type I interferon signalling in systemic lupus erythematosus. Arthritis Rheumatol 68:1222–1232

    PubMed  CAS  Google Scholar 

  148. Pauls E, Shapiro N, Peggie M, Young E, Sorcek R, Tan L et al (2012) Essential role for IKKb in production of type 1 interferons by plasmacytoid dendritic cells. J Biol Chem 287:19216–19228

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  149. Miyamoto R, Ito T, Nomura S, Amakawa R, Amuro H, Katashiba Y et al (2010) Inhibitor of IKB kinase activity, BAY 11–7082, interferes with interferon regulatory factor 7 nuclear translocation and type I interferon production by plasmacytoid dendritic cells. Arthritis Res Ther 12:R87

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  150. Wang H, Li T, Chen S, Gu Y, Ye S (2015) Neutrophil extracellular trap mitochondrial DNA and its autoantibody in systemic lupus erythematosus and a proof of concept trial of metformin. Arthritis Rheumatol 67:3190–3200

    Article  PubMed  CAS  Google Scholar 

  151. Oke V, Gunnarsson I, Dorschner J, Eketjäll S, Zickert A, Niewold T et al (2019) High levels of circulating interferons type I, type II and type III associate with distinct clinical features of active systemic lupus erythematosus. Arthritis Res Ther 21:107

    Article  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

Elaine Oon—Graphics.

Author information

Authors and Affiliations

  1. Department of Rheumatology, The Royal Melbourne Hospital, Parkville, VIC, Australia

    Shereen Oon

  2. Department of Rheumatology, St Vincent’s Hospital, Fitzroy, VIC, Australia

    Shereen Oon

  3. Department of Medicine at St Vincent’s Hospital, The University of Melbourne, Parkville, VIC, Australia

    Shereen Oon

Authors
  1. Shereen Oon
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Shereen Oon .

Editor information

Editors and Affiliations

  1. Department of Medicine, Monash University, Clayton, VIC, Australia

    Alberta Hoi

Rights and permissions

Reprints and permissions

Copyright information

© 2021 Springer Nature Switzerland AG

About this chapter

Check for updates. Verify currency and authenticity via CrossMark

Cite this chapter

Oon, S. (2021). Therapeutic Modulation of the Interferon Pathway in Systemic Lupus Erythematosus. In: Hoi, A. (eds) Pathogenesis of Systemic Lupus Erythematosus. Springer, Cham. https://doi.org/10.1007/978-3-030-85161-3_5

Download citation

Publish with us

Policies and ethics

Search

Navigation