A plasmacytoid dendritic cells-type I interferon axis is critically implicated in the pathogenesis of systemic lupus erythematosus

International Journal of Molecular Sciences

Volumn 16, Issue 6, 2015, Pages 14158-14170

  Kim, Ji Min ^a   Park, Sung Hwan ^b   Kim, Ho Youn ^c   Kwok, Seung Ki ^b  

^a Dongsan Medical Center   (South Korea)

^b The Catholic University of Korea   (South Korea)

^c Konkuk University Hospital   (South Korea)

Author keywords

Dendritic cells; Systemic lupus erythematosus; Type i interferon

Indexed keywords

ALPHA INTERFERON; ALPHA INTERFERON RECEPTOR; B7 ANTIGEN; CD4 ANTIGEN; CD40 ANTIGEN; CD8 ANTIGEN; CD86 ANTIGEN; CYTOTOXIC T LYMPHOCYTE ANTIGEN 4; HIGH MOBILITY GROUP B1 PROTEIN; INTERFERON; INTERFERON REGULATORY FACTOR 9; INTERFERON STIMULATED GENE FACTOR 3; INTERLEUKIN 17; INTERLEUKIN 6; JANUS KINASE 1; MITOGEN ACTIVATED PROTEIN KINASE; MYELOID DIFFERENTIATION FACTOR 88; PHOSPHATIDYLINOSITOL 3 KINASE; PROTEIN TYROSINE KINASE; RONTALIZUMAB; SIFALIMUMAB; STAT PROTEIN; TOLL LIKE RECEPTOR 7; TOLL LIKE RECEPTOR 9; TUMOR NECROSIS FACTOR ALPHA;

ADAPTIVE IMMUNITY; AUTOIMMUNITY; DRUG EFFICACY; DRUG SAFETY; HUMAN; IMMUNOLOGICAL TOLERANCE; IMMUNOPATHOGENESIS; INNATE IMMUNITY; NONHUMAN; PLASMACYTOID DENDRITIC CELL; PROTEIN EXPRESSION; REVIEW; SYSTEMIC LUPUS ERYTHEMATOSUS; TH17 CELL; ANIMAL; DENDRITIC CELL; METABOLISM; PATHOLOGY;

ANIMALS; DENDRITIC CELLS; HUMANS; INTERFERON TYPE I; LUPUS ERYTHEMATOSUS, SYSTEMIC;

EID: 84935006858     PISSN: 16616596     EISSN: 14220067     Source Type: Journal    
DOI: 10.3390/ijms160614158     Document Type: Review

References (76)

1. Rahman, A.; Isenberg, D.A. Systemic lupus erythematosus. N. Engl. J. Med. 2008, 358, 929–939.
2. Lisnevskaia, L.; Murphy, G.; Isenberg, D. Systemic lupus erythematosus. Lancet 2014, 384, 1878–1888.
3. Munoz, L.E.; Lauber, K.; Schiller, M.; Manfredi, A.A.; Herrmann, M. The role of defective clearance of apoptotic cells in systemic autoimmunity. Nat. Rev. Rheumatol. 2010, 6, 280–289.
4. Satpathy, A.T.; Wu, X.; Albring, J.C.; Murphy, K.M. Re(de)fining the dendritic cell lineage. Nat. Immunol. 2012, 13, 1145–1154.
5. Kadowaki, N.; Ho, S.; Antonenko, S.; Malefyt, R.W.; Kastelein, R.A.; Bazan, F.; Liu, Y.J. Subsets of human dendritic cell precursors express different toll-like receptors and respond to different microbial antigens. J. Exp. Med. 2001, 194, 863–869.
6. MacDonald, K.P.; Munster, D.J.; Clark, G.J.; Dzionek, A.; Schmitz, J.; Hart, D.N. Characterization of human blood dendritic cell subsets. Blood 2002, 100, 4512–4520.
7. Jego, G.; Palucka, A.K.; Blanck, J.P.; Chalouni, C.; Pascual, V.; Banchereau, J. Plasmacytoid dendritic cells induce plasma cell differentiation through type I interferon and interleukin 6. Immunity 2003, 19, 225–234.
8. Siegal, F.P.; Kadowaki, N.; Shodell, M.; Fitzgerald-Bocarsly, P.A.; Shah, K.; Ho, S.; Antonenko, S.; Liu, Y.J. The nature of the principal type I interferon-producing cells in human blood. Science 1999, 284, 1835–1837.
9. Shortman, K.; Liu, Y.J. Mouse and human dendritic cell subtypes. Nat. Rev. Immunol. 2002, 2, 151–161.
10. Kaisho, T. Pathogen sensors and chemokine receptors in dendritic cell subsets. Vaccine 2012, 30, 7652–7657.
11. Hawiger, D.; Inaba, K.; Dorsett, Y.; Guo, M.; Mahnke, K.; Rivera, M.; Ravetch, J.V.; Steinman, R.M.; Nussenzweig, M.C. Dendritic cells induce peripheral t cell unresponsiveness under steady state conditions in vivo. J. Exp. Med. 2001, 194, 769–779.
12. Kretschmer, K.; Apostolou, I.; Hawiger, D.; Khazaie, K.; Nussenzweig, M.C.; von Boehmer, H. Inducing and expanding regulatory t cell populations by foreign antigen. Nat. Immunol. 2005, 6, 1219–1227.
13. Bonasio, R.; Scimone, M.L.; Schaerli, P.; Grabie, N.; Lichtman, A.H.; von Andrian, U.H. Clonal deletion of thymocytes by circulating dendritic cells homing to the thymus. Nat. Immunol. 2006, 7, 1092–1100.
14. Proietto, A.I.; van Dommelen, S.; Zhou, P.; Rizzitelli, A.; D’Amico, A.; Steptoe, R.J.; Naik, S.H.; Lahoud, M.H.; Liu, Y.; Zheng, P.; et al. Dendritic cells in the thymus contribute to T-regulatory cell induction. Proc. Natl. Acad. Sci. USA 2008, 105, 19869–19874.
15. Probst, H.C.; McCoy, K.; Okazaki, T.; Honjo, T.; van den Broek, M. Resting dendritic cells induce peripheral CD8+ T cell tolerance through PD-1 and CTLA-4. Nat. Immunol. 2005, 6, 280–286.
16. Sela, U.; Olds, P.; Park, A.; Schlesinger, S.J.; Steinman, R.M. Dendritic cells induce antigen-specific regulatory T cells that prevent graft vs. host disease and persist in mice. J. Exp. Med. 2011, 208, 2489–2496.
17. Suffner, J.; Hochweller, K.; Kuhnle, M.C.; Li, X.; Kroczek, R.A.; Garbi, N.; Hammerling, G.J. Dendritic cells support homeostatic expansion of Foxp3+ regulatory t cells in Foxp3.Lucidtr mice. J. Immunol. 2010, 184, 1810–1820.
18. Coombes, J.L.; Siddiqui, K.R.; Arancibia-Carcamo, C.V.; Hall, J.; Sun, C.M.; Belkaid, Y.; Powrie, F. A functionally specialized population of mucosal cd103+ dcs induces Foxp3+ regulatory T cells via a TGF-β and retinoic acid-dependent mechanism. J. Exp. Med. 2007, 204, 1757–1764.
19. Bar-On, L.; Birnberg, T.; Kim, K.W.; Jung, S. Dendritic cell-restricted CD80/86 deficiency results in peripheral regulatory T-cell reduction but is not associated with lymphocyte hyperactivation. Eur. J. Immunol. 2011, 41, 291–298.
20. Teichmann, L.L.; Ols, M.L.; Kashgarian, M.; Reizis, B.; Kaplan, D.H.; Shlomchik, M.J. Dendritic cells in lupus are not required for activation of T and B cells but promote their expansion, resulting in tissue damage. Immunity 2010, 33, 967–978.
21. Stranges, P.B.; Watson, J.; Cooper, C.J.; Choisy-Rossi, C.M.; Stonebraker, A.C.; Beighton, R.A.; Hartig, H.; Sundberg, J.P.; Servick, S.; Kaufmann, G.; et al. Elimination of antigen-presenting cells and autoreactive T cells by fas contributes to prevention of autoimmunity. Immunity 2007, 26, 629–641.
22. Carreno, L.J.; Pacheco, R.; Gutierrez, M.A.; Jacobelli, S.; Kalergis, A.M. Disease activity in systemic lupus erythematosus is associated with an altered expression of low-affinity Fc y receptors and costimulatory molecules on dendritic cells. Immunology 2009, 128, 334-341.
23. Migita, K.; Miyashita, T.; Maeda, Y.; Kimura, H.; Nakamura, M.; Yatsuhashi, H.; Ishibashi, H.; Eguchi, K. Reduced blood BDCA-2+ (lymphoid) and CD11c+ (myeloid) dendritic cells in systemic lupus erythematosus. Clin. Exp. Immunol. 2005, 142, 84-91.
24. Fiore, N.; Castellano, G.; Blasi, A.; Capobianco, C.; Loverre, A.; Montinaro, V.; Netti, S.; Torres, D.; Manno, C.; Grandaliano, G.; et al. Immature myeloid and plasmacytoid dendritic cells infiltrate renal tubulointerstitium in patients with lupus nephritis. Mol. Immunol. 2008, 45, 259-265.
25. Tucci, M.; Quatraro, C.; Lombardi, L.; Pellegrino, C.; Dammacco, F.; Silvestris, F. Glomerular accumulation of plasmacytoid dendritic cells in active lupus nephritis: Role of interleukin-18. Arthritis Rheum. 2008, 58, 251-262.
26. Farkas, L.; Beiske, K.; Lund-Johansen, F.; Brandtzaeg, P.; Jahnsen, F.L. Plasmacytoid dendritic cells (natural interferon-a/p-producing cells) accumulate in cutaneous lupus erythematosus lesions. Am. J. Pathol. 2001, 159, 237-243.
27. Blomberg, S.; Eloranta, ML.; Cederblad, B.; Nordlin, K.; Alm, GV.; Ronnblom, L. Presence of cutaneous interferon-a producing cells in patients with systemic lupus erythematosus. Lupus 2001, 10, 484-490.
28. Kwok, S.K.; Lee, J.Y.; Park, S.H.; Cho, ML.; Min, S.Y.; Park, S.H.; Kim, H.Y.; Cho, Y.G. Dysfunctional interferon-a production by peripheral plasmacytoid dendritic cells upon toll-like receptor-9 stimulation in patients with systemic lupus erythematosus. Arthritis Res. Ther. 2008, 10, doi:10.1126/scitranslmed.3001180.
29. Nie, Y.J.; Mok, M.Y.; Chan, G.C.; Chan, A.W.; Jin, O.U.; Kavikondala, S.; Lie, A.K.; Lau, C.S. Phenotypic and functional abnormalities of bone marrow-derived dendritic cells in systemic lupus erythematosus. Arthritis Res. Ther. 2010, 12, doi:10.1186/ar3018.
30. Gerl, V.; Lischka, A.; Panne, D.; Grossmann, P.; Berthold, R.; Hoyer, B.F.; Biesen, R.; Bruns, A.; Alexander, T.; Jacobi, A.; et al. Blood dendritic cells in systemic lupus erythematosus exhibit altered activation state and chemokine receptor function. Ann. Rheum. Dis. 2010, 69, 1370-1377.
31. Wittamer, V.; Franssen, J.D.; Vulcano, M.; Mirjolet, J.F.; le Poul, E.; Migeotte, I.; Brezillon, S.; Tyldesley, R.; Blanpain, C.; Detheux, M.; et al. Specific recruitment of antigen-presenting cells by chemerin, a novel processed ligand from human inflammatory fluids. J. Exp. Med. 2003, 198, 977-985.
32. Vermi, W.; Riboldi, E.; Wittamer, V.; Gentili, F.; Luini, W.; Marrelli, S.; Vecchi, A.; Franssen, J.D.; Communi, D.; Massardi, L.; et al. Role of chemr23 in directing the migration of myeloid and plasmacytoid dendritic cells to lymphoid organs and inflamed skin. J. Exp. Med. 2005, 201, 509-515.
33. Jin, O.; Kavikondala, S.; Mok, M.Y.; Sun, L.; Gu, J.; Fu, R.; Chan, A.; Yeung, J.; Nie, Y.; Lau, C.S. Abnormalities in circulating plasmacytoid dendritic cells in patients with systemic lupus erythematosus. Arthritis Res. Ther. 2010, 12, doi:10.1186/ar3075.
34. Rowland, S.L.; Riggs, J.M.; Gilfillan, S.; Bugatti, M.; Vermi, W.; Kolbeck, R.; Unanue, E.R.; Sanjuan, M.A.; Colonna, M. Early, transient depletion of plasmacytoid dendritic cells ameliorates autoimmunity in a lupus model. J. Exp. Med. 2014, 211, 1977–1991.
35. Barrat, F.J.; Meeker, T.; Gregorio, J.; Chan, J.H.; Uematsu, S.; Akira, S.; Chang, B.; Duramad, O.; Coffman, R.L. Nucleic acids of mammalian origin can act as endogenous ligands for toll-like receptors and may promote systemic lupus erythematosus. J. Exp. Med. 2005, 202, 1131–1139.
36. Lovgren, T.; Eloranta, M.L.; Bave, U.; Alm, G.V.; Ronnblom, L. Induction of interferon-α production in plasmacytoid dendritic cells by immune complexes containing nucleic acid released by necrotic or late apoptotic cells and lupus IgG. Arthritis Rheum. 2004, 50, 1861–1872.
37. Christensen, S.R.; Shupe, J.; Nickerson, K.; Kashgarian, M.; Flavell, R.A.; Shlomchik, M.J. Toll-like receptor 7 and TLR9 dictate autoantibody specificity and have opposing inflammatory and regulatory roles in a murine model of lupus. Immunity 2006, 25, 417–428.
38. Deane, J.A.; Pisitkun, P.; Barrett, R.S.; Feigenbaum, L.; Town, T.; Ward, J.M.; Flavell, R.A.; Bolland, S. Control of toll-like receptor 7 expression is essential to restrict autoimmunity and dendritic cell proliferation. Immunity 2007, 27, 801–810.
39. Karrich, J.J.; Jachimowski, L.C.; Uittenbogaart, C.H.; Blom, B. The plasmacytoid dendritic cell as the swiss army knife of the immune system: Molecular regulation of its multifaceted functions. J. Immunol. 2014, 193, 5772–5778.
40. Honda, K.; Yanai, H.; Negishi, H.; Asagiri, M.; Sato, M.; Mizutani, T.; Shimada, N.; Ohba, Y.; Takaoka, A.; Yoshida, N.; et al. IRF-7 is the master regulator of type-I interferon-dependent immune responses. Nature 2005, 434, 772–777.
41. Garcia-Romo, G.S.; Caielli, S.; Vega, B.; Connolly, J.; Allantaz, F.; Xu, Z.; Punaro, M.; Baisch, J.; Guiducci, C.; Coffman, R.L.; et al. Netting neutrophils are major inducers of type I IFN production in pediatric systemic lupus erythematosus. Sci. Transl. Med. 2011, 3, doi:10.1126/scitranslmed.3001201.
42. Tian, J.; Avalos, A.M.; Mao, S.Y.; Chen, B.; Senthil, K.; Wu, H.; Parroche, P.; Drabic, S.; Golenbock, D.; Sirois, C.; et al. Toll-like receptor 9-dependent activation by DNA-containing immune complexes is mediated by HMGB1 and rage. Nat. Immunol. 2007, 8, 487–496.
43. Lande, R.; Ganguly, D.; Facchinetti, V.; Frasca, L.; Conrad, C.; Gregorio, J.; Meller, S.; Chamilos, G.; Sebasigari, R.; Riccieri, V.; et al. Neutrophils activate plasmacytoid dendritic cells by releasing self-DNA-peptide complexes in systemic lupus erythematosus. Sci. Transl. Med. 2011, 3, doi:10.1126/scitranslmed.3001180.
44. Baechler, E.C.; Batliwalla, F.M.; Karypis, G.; Gaffney, P.M.; Ortmann, W.A.; Espe, K.J.; Shark, K.B.; Grande, W.J.; Hughes, K.M.; Kapur, V.; et al. Interferon-inducible gene expression signature in peripheral blood cells of patients with severe lupus. Proc. Natl. Acad. Sci. USA 2003, 100, 2610–2615.
45. Reizis, B.; Colonna, M.; Trinchieri, G.; Barrat, F.; Gilliet, M. Plasmacytoid dendritic cells: One-trick ponies or workhorses of the immune system? Nat. Rev. Immunol. 2011, 11, 558–565.
46. Schilling, P.J.; Kurzrock, R.; Kantarjian, H.; Gutterman, J.U.; Talpaz, M. Development of systemic lupus erythematosus after interferon therapy for chronic myelogenous leukemia. Cancer 1991, 68, 1536–1537.
47. Ho, V.; McLean, A.; Terry, S. Severe systemic lupus erythematosus induced by antiviral treatment for hepatitis C. J. Clin. Rheumatol. Pract. Rep. Rheum. Musculoskelet. Dis. 2008, 14, 166–168.
48. Dall’era, M.C.; Cardarelli, P.M.; Preston, B.T.; Witte, A.; Davis, J.C., Type I interferon correlates with serological and clinical manifestations of SLE. Ann. Rheum. Dis. 2005, 64, 1692–1697.
49. Postal, M.; Sinicato, N.A.; Pelicari, K.O.; Marini, R.; Lavras Costallat, L.T.; Appenzeller, S. Clinical and serological manifestations associated with interferon-α levels in childhood-onset systemic lupus erythematosus. Clinics 2012, 67, 157–162.
50. Bennett, L.; Palucka, A.K.; Arce, E.; Cantrell, V.; Borvak, J.; Banchereau, J.; Pascual, V. Interferon and granulopoiesis signatures in systemic lupus erythematosus blood. J. Exp. Med. 2003, 197, 711–723.
51. Lin, Q.; Dong, C.; Cooper, M.D. Impairment of t and B cell development by treatment with a type I interferon. J. Exp. Med. 1998, 187, 79–87.
52. Lood, C.; Tyden, H.; Gullstrand, B.; Klint, C.; Wenglen, C.; Nielsen, C.T.; Heegaard, N.H.; Jonsen, A.; Kahn, R.; Bengtsson, A.A. Type I interferon-mediated skewing of the serotonin synthesis is associated with severe disease in systemic lupus erythematosus. PLoS ONE 2015, 10, e0125109.
53. Blanco, P.; Palucka, A.K.; Gill, M.; Pascual, V.; Banchereau, J. Induction of dendritic cell differentiation by IFN-α in systemic lupus erythematosus. Science 2001, 294, 1540–1543.
54. Longhi, M.P.; Trumpfheller, C.; Idoyaga, J.; Caskey, M.; Matos, I.; Kluger, C.; Salazar, A.M.; Colonna, M.; Steinman, R.M. Dendritic cells require a systemic type I interferon response to mature and induce CD4+ Th1 immunity with poly IC as adjuvant. J. Exp. Med. 2009, 206, 1589–1602.
55. Le Bon, A.; Etchart, N.; Rossmann, C.; Ashton, M.; Hou, S.; Gewert, D.; Borrow, P.; Tough, D.F. Cross-priming of CD8+ T cells stimulated by virus-induced type I interferon. Nat. Immunol. 2003, 4, 1009–1015.
56. Curtsinger, J.M.; Valenzuela, J.O.; Agarwal, P.; Lins, D.; Mescher, M.F. Type I IFNs provide a third signal to CD8 T cells to stimulate clonal expansion and differentiation. J. Immunol. 2005, 174, 4465–4469.
57. Biron, C.A.; Nguyen, K.B.; Pien, G.C.; Cousens, L.P.; Salazar-Mather, T.P. Natural killer cells in antiviral defense: Function and regulation by innate cytokines. Ann. Rev. Immunol. 1999, 17, 189–220.
58. Le Bon, A.; Schiavoni, G.; D’Agostino, G.; Gresser, I.; Belardelli, F.; Tough, D.F. Type I interferons potently enhance humoral immunity and can promote isotype switching by stimulating dendritic cells in vivo. Immunity 2001, 14, 461–470.
59. Yasuda, K.; Richez, C.; Maciaszek, J.W.; Agrawal, N.; Akira, S.; Marshak-Rothstein, A.; Rifkin, I.R. Murine dendritic cell type I IFN production induced by human IgG-RNA immune complexes is IFN regulatory factor (IRF) 5 and IRF7 dependent and is required for ILl–6 production. J. Immunol. 2007, 178, 6876–6885.
60. Ambrosi, A.; Espinosa, A.; Wahren-Herlenius, M. IL-17: A new actor in IFN-driven systemic autoimmune diseases. Eur. J. Immunol. 2012, 42, 2274–2284.
61. Doreau, A.; Belot, A.; Bastid, J.; Riche, B.; Trescol-Biemont, M.C.; Ranchin, B.; Fabien, N.; Cochat, P.; Pouteil-Noble, C.; Trolliet, P.; et al. Interleukin 17 acts in synergy with B cell-activating factor to influence B cell biology and the pathophysiology of systemic lupus erythematosus. Nat. Immunol. 2009, 10, 778–785.
62. Gaffen, S.L. An overview of IL-17 function and signaling. Cytokine 2008, 43, 402–407.
63. Ozaki, K.; Spolski, R.; Ettinger, R.; Kim, H.P.; Wang, G.; Qi, C.F.; Hwu, P.; Shaffer, D.J.; Akilesh, S.; Roopenian, D.C.; et al. Regulation of B cell differentiation and plasma cell generation by IL-21, a novel inducer of Blimp-1 and Bcl-6. J. Immunol. 2004, 173, 5361–5371.
64. Vogelzang, A.; McGuire, H.M.; Yu, D.; Sprent, J.; Mackay, C.R.; King, C. A fundamental role for interleukin-21 in the generation of t follicular helper cells. Immunity 2008, 29, 127–137.
65. Nzeusseu Toukap, A.; Galant, C.; Theate, I.; Maudoux, A.L.; Lories, R.J.; Houssiau, F.A.; Lauwerys, B.R. Identification of distinct gene expression profiles in the synovium of patients with systemic lupus erythematosus. Arthritis Rheum. 2007, 56, 1579–1588.
66. Peterson, K.S.; Huang, J.F.; Zhu, J.; D’Agati, V.; Liu, X.; Miller, N.; Erlander, M.G.; Jackson, M.R.; Winchester, R.J. Characterization of heterogeneity in the molecular pathogenesis of lupus nephritis from transcriptional profiles of laser-captured glomeruli. J. Clin. Investig. 2004, 113, 1722–1733.
67. Liu, Z.; Bethunaickan, R.; Huang, W.; Lodhi, U.; Solano, I.; Madaio, M.P.; Davidson, A. Interferon-α accelerates murine systemic lupus erythematosus in a T cell-dependent manner. Arthritis Rheum. 2011, 63, 219–229.
68. Migliorini, A.; Angelotti, M.L.; Mulay, S.R.; Kulkarni, O.O.; Demleitner, J.; Dietrich, A.; Sagrinati, C.; Ballerini, L.; Peired, A.; Shankland, S.J.; et al. The antiviral cytokines IFN-α and IFN-β modulate parietal epithelial cells and promote podocyte loss: Implications for IFN toxicity, viral glomerulonephritis, and glomerular regeneration. Am. J. Pathol. 2013, 183, 431–440.
69. Denny, M.F.; Thacker, S.; Mehta, H.; Somers, E.C.; Dodick, T.; Barrat, F.J.; McCune, W.J.; Kaplan, M.J. Interferon-α promotes abnormal vasculogenesis in lupus: A potential pathway for premature atherosclerosis. Blood 2007, 110, 2907–2915.
70. Thacker, S.G.; Zhao, W.; Smith, C.K.; Luo, W.; Wang, H.; Vivekanandan-Giri, A.; Rabquer, B.J.; Koch, A.E.; Pennathur, S.; Davidson, A.; et al. Type I interferons modulate vascular function, repair, thrombosis, and plaque progression in murine models of lupus and atherosclerosis. Arthritis Rheum. 2012, 64, 2975–2985.
71. Santer, D.M.; Yoshio, T.; Minota, S.; Moller, T.; Elkon, K.B. Potent induction of IFN-α and chemokines by autoantibodies in the cerebrospinal fluid of patients with neuropsychiatric lupus. J. Immunol. 2009, 182, 1192–1201.
72. Merrill, J.T.; Wallace, D.J.; Petri, M.; Kirou, K.A.; Yao, Y.; White, W.I.; Robbie, G.; Levin, R.; Berney, S.M.; Chindalore, V.; et al. Safety profile and clinical activity of sifalimumab, a fully human anti-interferon alpha monoclonal antibody, in systemic lupus erythematosus: A phase I, multicentre, double-blind randomised study. Ann. Rheum. Dis. 2011, 70, 1905–1913.
73. Petri, M.; Wallace, D.J.; Spindler, A.; Chindalore, V.; Kalunian, K.; Mysler, E.; Neuwelt, C.M.; Robbie, G.; White, W.I.; Higgs, B.W.; et al. Sifalimumab, a human anti-interferon-α monoclonal antibody, in systemic lupus erythematosus: A phase I randomized, controlled, dose-escalation study. Arthritis Rheum. 2013, 65, 1011–1021.
74. McBride, J.M.; Jiang, J.; Abbas, A.R.; Morimoto, A.; Li, J.; Maciuca, R.; Townsend, M.; Wallace, D.J.; Kennedy, W.P.; Drappa, J. Safety and pharmacodynamics of rontalizumab in patients with systemic lupus erythematosus: Results of a phase I, placebo-controlled, double-blind, dose-escalation study. Arthritis Rheum. 2012, 64, 3666–3676.
75. Lauwerys, B.R.; Hachulla, E.; Spertini, F.; Lazaro, E.; Jorgensen, C.; Mariette, X.; Haelterman, E.; Grouard-Vogel, G.; Fanget, B.; Dhellin, O.; et al. Down-regulation of interferon signature in systemic lupus erythematosus patients by active immunization with interferon α-kinoid. Arthritis Rheum. 2013, 65, 447–456.
76. Li, J.; Wang, X.; Zhang, F.; Yin, H. Toll-like receptors as therapeutic targets for autoimmune connective tissue diseases. Pharmacol. Ther. 2013, 138, 441–451.