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Type I Interferonopathies: From Pathophysiology to Clinical Expression

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Auto-Inflammatory Syndromes

Abstract

Type I interferonopathies are a diverse group of monogenic diseases which hallmarked the type I interferon (IFN) pathway activation. Abnormal accumulation of endogenous nucleic acids, excessive sensitivity or activity of DNA/RNA sensors, and the dysregulation of type I IFN pathway have been identified as the main contributors to excessive type I IFN signaling in this setting. Chilblain-like lesions, central nervous system calcifications, interstitial lung disease, and growth retardation are among the most common features shared by the majority of type I interferonopathies. Targeting of type I IFN signaling seems to hold a promising therapeutic role.

Authors Christina Maria Flessa and Evangelia Argiriou are equally contributed to this work.

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References

  1. Rodero MP, Crow YJ. Type I interferon-mediated monogenic autoinflammation: the type I interferonopathies, a conceptual overview. J Exp Med. 2016;213(12):2527–38.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Isaacs A, Lindenmann J. Virus interference. I. The interferon. Proc R Soc Lond B Biol Sci. 1957;147(927):258–67.

    Article  CAS  PubMed  Google Scholar 

  3. Isaacs A, Lindenmann J, Valentine RC. Virus interference. II. Some properties of interferon. Proc R Soc Lond B Biol Sci. 1957;147(927):268–73.

    Article  CAS  PubMed  Google Scholar 

  4. Mavragani CP, Crow MK. Activation of the type I interferon pathway in primary Sjogren's syndrome. J Autoimmun. 2010;35(3):225–31.

    Article  CAS  PubMed  Google Scholar 

  5. Hooks JJ, et al. Immune interferon in the circulation of patients with autoimmune disease. N Engl J Med. 1979;301(1):5–8.

    Article  CAS  PubMed  Google Scholar 

  6. Crow MK. Type I interferon in the pathogenesis of lupus. J Immunol. 2014;192(12):5459–68.

    Article  CAS  PubMed  Google Scholar 

  7. Kim D, et al. Induction of interferon-alpha by scleroderma sera containing autoantibodies to topoisomerase I: association of higher interferon-alpha activity with lung fibrosis. Arthritis Rheum. 2008;58(7):2163–73.

    Article  CAS  PubMed  Google Scholar 

  8. Nezos A, et al. Type I and II interferon signatures in Sjogren's syndrome pathogenesis: contributions in distinct clinical phenotypes and Sjogren's related lymphomagenesis. J Autoimmun. 2015;63:47–58.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Vakaloglou KM, Mavragani CP. Activation of the type I interferon pathway in primary Sjogren’s syndrome: an update. Curr Opin Rheumatol. 2011;23(5):459–64.

    Article  CAS  PubMed  Google Scholar 

  10. Gresser I, et al. Interferon-induced disease in mice and rats. Ann N Y Acad Sci. 1980;350:12–20.

    Article  CAS  PubMed  Google Scholar 

  11. Aicardi J, Goutieres F. A progressive familial encephalopathy in infancy with calcifications of the basal ganglia and chronic cerebrospinal fluid lymphocytosis. Ann Neurol. 1984;15(1):49–54.

    Article  CAS  PubMed  Google Scholar 

  12. Lebon P, et al. Intrathecal synthesis of interferon-alpha in infants with progressive familial encephalopathy. J Neurol Sci. 1988;84(2–3):201–8.

    Article  CAS  PubMed  Google Scholar 

  13. Crow YJ, et al. Cree encephalitis is allelic with Aicardi-Goutieres syndrome: implications for the pathogenesis of disorders of interferon alpha metabolism. J Med Genet. 2003;40(3):183–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Akwa Y, et al. Transgenic expression of IFN-alpha in the central nervous system of mice protects against lethal neurotropic viral infection but induces inflammation and neurodegeneration. J Immunol. 1998;161(9):5016–26.

    CAS  PubMed  Google Scholar 

  15. Campbell IL, et al. Structural and functional neuropathology in transgenic mice with CNS expression of IFN-alpha. Brain Res. 1999;835(1):46–61.

    Article  CAS  PubMed  Google Scholar 

  16. Kavanagh D, et al. Type I interferon causes thrombotic microangiopathy by a dose-dependent toxic effect on the microvasculature. Blood. 2016;128(24):2824–33.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Ivashkiv LB, Donlin LT. Regulation of type I interferon responses. Nat Rev Immunol. 2014;14(1):36–49.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. de Weerd NA, et al. Structural basis of a unique interferon-beta signaling axis mediated via the receptor IFNAR1. Nat Immunol. 2013;14(9):901–7.

    Article  PubMed  CAS  Google Scholar 

  19. Mostafavi S, et al. Parsing the interferon transcriptional network and its disease associations. Cell. 2016;164(3):564–78.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Muller M, et al. The protein tyrosine kinase JAK1 complements defects in interferon-alpha/beta and -gamma signal transduction. Nature. 1993;366(6451):129–35.

    Article  CAS  PubMed  Google Scholar 

  21. Stark GR, Darnell JE Jr. The JAK-STAT pathway at twenty. Immunity. 2012;36(4):503–14.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Velazquez L, et al. A protein tyrosine kinase in the interferon alpha/beta signaling pathway. Cell. 1992;70(2):313–22.

    Article  CAS  PubMed  Google Scholar 

  23. Blaszczyk K, et al. STAT2/IRF9 directs a prolonged ISGF3-like transcriptional response and antiviral activity in the absence of STAT1. Biochem J. 2015;466(3):511–24.

    Article  CAS  PubMed  Google Scholar 

  24. Bluyssen HA, Levy DE. Stat2 is a transcriptional activator that requires sequence-specific contacts provided by stat1 and p48 for stable interaction with DNA. J Biol Chem. 1997;272(7):4600–5.

    Article  CAS  PubMed  Google Scholar 

  25. Uddin S, Platanias LC. Mechanisms of type-I interferon signal transduction. J Biochem Mol Biol. 2004;37(6):635–41.

    CAS  PubMed  Google Scholar 

  26. Medzhitov R, Preston-Hurlburt P, Janeway CA Jr. A human homologue of the Drosophila Toll protein signals activation of adaptive immunity. Nature. 1997;388(6640):394–7.

    Article  CAS  PubMed  Google Scholar 

  27. Lamkanfi M, Dixit VM. Inflammasomes and their roles in health and disease. Annu Rev Cell Dev Biol. 2012;28:137–61.

    Article  CAS  PubMed  Google Scholar 

  28. Paludan SR, Bowie AG. Immune sensing of DNA. Immunity. 2013;38(5):870–80.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Vidya MK, et al. Toll-like receptors: significance, ligands, signaling pathways, and functions in mammals. Int Rev Immunol. 2018;37(1):20–36.

    Article  CAS  PubMed  Google Scholar 

  30. Wu J, Chen ZJ. Innate immune sensing and signaling of cytosolic nucleic acids. Annu Rev Immunol. 2014;32:461–88.

    Article  CAS  PubMed  Google Scholar 

  31. Kawai T, Akira S. The role of pattern-recognition receptors in innate immunity: update on Toll-like receptors. Nat Immunol. 2010;11(5):373–84.

    Article  CAS  PubMed  Google Scholar 

  32. Yoneyama M, et al. Shared and unique functions of the DExD/H-box helicases RIG-I, MDA5, and LGP2 in antiviral innate immunity. J Immunol. 2005;175(5):2851–8.

    Article  CAS  PubMed  Google Scholar 

  33. Seth RB, et al. Identification and characterization of MAVS, a mitochondrial antiviral signaling protein that activates NF-kappaB and IRF 3. Cell. 2005;122(5):669–82.

    Article  CAS  PubMed  Google Scholar 

  34. Silverman RH. Viral encounters with 2′,5′-oligoadenylate synthetase and RNase L during the interferon antiviral response. J Virol. 2007;81(23):12720–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Diebold SS, et al. Viral infection switches non-plasmacytoid dendritic cells into high interferon producers. Nature. 2003;424(6946):324–8.

    Article  CAS  PubMed  Google Scholar 

  36. Chiu YH, Macmillan JB, Chen ZJ. RNA polymerase III detects cytosolic DNA and induces type I interferons through the RIG-I pathway. Cell. 2009;138(3):576–91.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Ishikawa H, Barber GN. STING is an endoplasmic reticulum adaptor that facilitates innate immune signalling. Nature. 2008;455(7213):674–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Tanaka Y, Chen ZJ. STING specifies IRF3 phosphorylation by TBK1 in the cytosolic DNA signaling pathway. Sci Signal. 2012;5(214):ra20.

    Article  PubMed  PubMed Central  Google Scholar 

  39. Du XX, Su XD. Detection of cyclic dinucleotides by STING. Methods Mol Biol. 2017;1657:59–69.

    Article  CAS  PubMed  Google Scholar 

  40. Burdette DL, et al. STING is a direct innate immune sensor of cyclic di-GMP. Nature. 2011;478(7370):515–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Xiao TS, Fitzgerald KA. The cGAS-STING pathway for DNA sensing. Mol Cell. 2013;51(2):135–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Sun L, et al. Cyclic GMP-AMP synthase is a cytosolic DNA sensor that activates the type I interferon pathway. Science. 2013;339(6121):786–91.

    Article  CAS  PubMed  Google Scholar 

  43. Wu J, et al. Cyclic GMP-AMP is an endogenous second messenger in innate immune signaling by cytosolic DNA. Science. 2013;339(6121):826–30.

    Article  CAS  PubMed  Google Scholar 

  44. Stetson DB, et al. Trex1 prevents cell-intrinsic initiation of autoimmunity. Cell. 2008;134(4):587–98.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Crow YJ. The story of DNase II: a stifled death-wish leads to self-harm. Eur J Immunol. 2010;40(9):2376–8.

    Article  CAS  PubMed  Google Scholar 

  46. Burckstummer T, et al. An orthogonal proteomic-genomic screen identifies AIM2 as a cytoplasmic DNA sensor for the inflammasome. Nat Immunol. 2009;10(3):266–72.

    Article  PubMed  CAS  Google Scholar 

  47. Picard C, Belot A. Does type-I interferon drive systemic autoimmunity? Autoimmun Rev. 2017;16(9):897–902.

    Article  CAS  PubMed  Google Scholar 

  48. Mavragani CP, et al. Defective regulation of L1 endogenous retroelements in primary Sjogren’s syndrome and systemic lupus erythematosus: role of methylating enzymes. J Autoimmun. 2018;88:75–82.

    Article  CAS  PubMed  Google Scholar 

  49. Mavragani CP, et al. Expression of long interspersed nuclear element 1 retroelements and induction of type I interferon in patients with systemic autoimmune disease. Arthritis Rheumatol. 2016;68(11):2686–96.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. Melki I, et al. Disease-associated mutations identify a novel region in human STING necessary for the control of type I interferon signaling. J Allergy Clin Immunol. 2017;140(2):543–52. e5

    Article  CAS  PubMed  Google Scholar 

  51. Warner JD, et al. STING-associated vasculopathy develops independently of IRF3 in mice. J Exp Med. 2017;214:3279–92.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  52. Jeremiah N, et al. Inherited STING-activating mutation underlies a familial inflammatory syndrome with lupus-like manifestations. J Clin Invest. 2014;124(12):5516–20.

    Article  PubMed  PubMed Central  Google Scholar 

  53. Liu Y, et al. Activated STING in a vascular and pulmonary syndrome. N Engl J Med. 2014;371(6):507–18.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  54. Kim H, Sanchez GA, Goldbach-Mansky R. Insights from Mendelian interferonopathies: comparison of CANDLE, SAVI with AGS, monogenic lupus. J Mol Med (Berl). 2016;94(10):1111–27.

    Article  CAS  Google Scholar 

  55. Richards A, et al. C-terminal truncations in human 3′-5′ DNA exonuclease TREX1 cause autosomal dominant retinal vasculopathy with cerebral leukodystrophy. Nat Genet. 2007;39(9):1068–70.

    Article  CAS  PubMed  Google Scholar 

  56. Schuh E, et al. Multiple sclerosis-like lesions and type I interferon signature in a patient with RVCL. Neurol Neuroimmunol Neuroinflamm. 2015;2(1):e55.

    Article  PubMed  Google Scholar 

  57. Feigenbaum A, et al. Singleton-Merten syndrome: an autosomal dominant disorder with variable expression. Am J Med Genet A. 2013;161A(2):360–70.

    Article  PubMed  Google Scholar 

  58. Jang MA, et al. Mutations in DDX58, which encodes RIG-I, cause atypical Singleton-Merten syndrome. Am J Hum Genet. 2015;96(2):266–74.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  59. Lee-Kirsch MA. The type I interferonopathies. Annu Rev Med. 2017;68:297–315.

    Article  CAS  PubMed  Google Scholar 

  60. Rutsch F, et al. A specific IFIH1 gain-of-function mutation causes Singleton-Merten syndrome. Am J Hum Genet. 2015;96(2):275–82.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  61. de Carvalho LM, et al. Musculoskeletal disease in MDA5-related type I interferonopathy: a Mendelian mimic of Jaccoud’s arthropathy. Arthritis Rheumatol. 2017;69(10):2081–91.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  62. Chahwan C, Chahwan R. Aicardi-Goutieres syndrome: from patients to genes and beyond. Clin Genet. 2012;81(5):413–20.

    Article  CAS  PubMed  Google Scholar 

  63. Barth PG. The neuropathology of Aicardi-Goutieres syndrome. Eur J Paediatr Neurol. 2002;6(Suppl A):A27–31; discussion A37–9, A77–86.

    Article  PubMed  Google Scholar 

  64. Ekholm L, et al. Autoantibody specificities and type I interferon pathway activation in idiopathic inflammatory myopathies. Scand J Immunol. 2016;84(2):100–9.

    Article  CAS  PubMed  Google Scholar 

  65. Eloranta ML, Ronnblom L. Cause and consequences of the activated type I interferon system in SLE. J Mol Med (Berl). 2016;94(10):1103–10.

    Article  Google Scholar 

  66. Crow YJ, Manel N. Aicardi-Goutieres syndrome and the type I interferonopathies. Nat Rev Immunol. 2015;15(7):429–40.

    Article  CAS  PubMed  Google Scholar 

  67. Ablasser A, et al. TREX1 deficiency triggers cell-autonomous immunity in a cGAS-dependent manner. J Immunol. 2014;192(12):5993–7.

    Article  CAS  PubMed  Google Scholar 

  68. Mackenzie KJ, et al. Ribonuclease H2 mutations induce a cGAS/STING-dependent innate immune response. EMBO J. 2016;35(8):831–44.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  69. Clifford R, et al. SAMHD1 is mutated recurrently in chronic lymphocytic leukemia and is involved in response to DNA damage. Blood. 2014;123(7):1021–31.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  70. Kretschmer S, et al. SAMHD1 prevents autoimmunity by maintaining genome stability. Ann Rheum Dis. 2015;74(3):e17.

    Article  PubMed  CAS  Google Scholar 

  71. Maelfait J, et al. Restriction by SAMHD1 limits cGAS/STING-dependent innate and adaptive immune responses to HIV-1. Cell Rep. 2016;16(6):1492–501.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  72. Mannion NM, et al. The RNA-editing enzyme ADAR1 controls innate immune responses to RNA. Cell Rep. 2014;9(4):1482–94.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  73. Vitali P, Scadden AD. Double-stranded RNAs containing multiple IU pairs are sufficient to suppress interferon induction and apoptosis. Nat Struct Mol Biol. 2010;17(9):1043–50.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  74. Hayashi M, Suzuki T. Dyschromatosis symmetrica hereditaria. J Dermatol. 2013;40(5):336–43.

    Article  CAS  PubMed  Google Scholar 

  75. Funabiki M, et al. Autoimmune disorders associated with gain of function of the intracellular sensor MDA5. Immunity. 2014;40(2):199–212.

    Article  CAS  PubMed  Google Scholar 

  76. Oda H, et al. Aicardi-Goutieres syndrome is caused by IFIH1 mutations. Am J Hum Genet. 2014;95(1):121–5.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  77. Fiehn C. Familial chilblain lupus - what can we learn from type I interferonopathies? Curr Rheumatol Rep. 2017;19(10):61.

    Article  PubMed  CAS  Google Scholar 

  78. Lee-Kirsch MA, et al. A mutation in TREX1 that impairs susceptibility to granzyme A-mediated cell death underlies familial chilblain lupus. J Mol Med (Berl). 2007;85(5):531–7.

    Article  CAS  Google Scholar 

  79. Lee-Kirsch MA, et al. Familial chilblain lupus, a monogenic form of cutaneous lupus erythematosus, maps to chromosome 3p. Am J Hum Genet. 2006;79(4):731–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  80. Briggs TA, et al. Spondyloenchondrodysplasia due to mutations in ACP5: a comprehensive survey. J Clin Immunol. 2016;36(3):220–34.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  81. Lausch E, et al. Genetic deficiency of tartrate-resistant acid phosphatase associated with skeletal dysplasia, cerebral calcifications and autoimmunity. Nat Genet. 2011;43(2):132–7.

    Article  CAS  PubMed  Google Scholar 

  82. An J, et al. Tartrate-resistant acid phosphatase deficiency in the predisposition to systemic lupus erythematosus. Arthritis Rheumatol. 2017;69(1):131–42.

    Article  CAS  PubMed  Google Scholar 

  83. Briggs TA, et al. Tartrate-resistant acid phosphatase deficiency causes a bone dysplasia with autoimmunity and a type I interferon expression signature. Nat Genet. 2011;43(2):127–31.

    Article  CAS  PubMed  Google Scholar 

  84. Navarro V, et al. Two further cases of spondyloenchondrodysplasia (SPENCD) with immune dysregulation. Am J Med Genet A. 2008;146A(21):2810–5.

    Article  CAS  PubMed  Google Scholar 

  85. Renella R, et al. Spondyloenchondrodysplasia with spasticity, cerebral calcifications, and immune dysregulation: clinical and radiographic delineation of a pleiotropic disorder. Am J Med Genet A. 2006;140(6):541–50.

    Article  PubMed  Google Scholar 

  86. Roifman CM, Melamed I. A novel syndrome of combined immunodeficiency, autoimmunity and spondylometaphyseal dysplasia. Clin Genet. 2003;63(6):522–9.

    Article  CAS  PubMed  Google Scholar 

  87. Schorr S, Legum C, Ochshorn M. Spondyloenchondrodysplasia. Enchondromatomosis with severe platyspondyly in two brothers. Radiology. 1976;118(1):133–9.

    Article  CAS  PubMed  Google Scholar 

  88. Zhang X, et al. Human intracellular ISG15 prevents interferon-alpha/beta over-amplification and auto-inflammation. Nature. 2015;517(7532):89–93.

    Article  CAS  PubMed  Google Scholar 

  89. Bogunovic D, et al. Mycobacterial disease and impaired IFN-gamma immunity in humans with inherited ISG15 deficiency. Science. 2012;337(6102):1684–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  90. Meuwissen ME, et al. Human USP18 deficiency underlies type 1 interferonopathy leading to severe pseudo-TORCH syndrome. J Exp Med. 2016;213(7):1163–74.

    Article  PubMed  PubMed Central  Google Scholar 

  91. Brehm A, et al. Additive loss-of-function proteasome subunit mutations in CANDLE/PRAAS patients promote type I IFN production. J Clin Invest. 2015;125(11):4196–211.

    Article  PubMed  PubMed Central  Google Scholar 

  92. Torrelo A. CANDLE syndrome as a paradigm of proteasome-related autoinflammation. Front Immunol. 2017;8:927.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  93. Castanier C, et al. MAVS ubiquitination by the E3 ligase TRIM25 and degradation by the proteasome is involved in type I interferon production after activation of the antiviral RIG-I-like receptors. BMC Biol. 2012;10:44.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  94. Tufekci O, et al. CANDLE syndrome: a recently described autoinflammatory syndrome. J Pediatr Hematol Oncol. 2015;37(4):296–9.

    Article  PubMed  Google Scholar 

  95. Starokadomskyy P, et al. DNA polymerase-alpha regulates the activation of type I interferons through cytosolic RNA:DNA synthesis. Nat Immunol. 2016;17(5):495–504.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  96. Pezzani L, et al. X-linked reticulate pigmentary disorder with systemic manifestations: a new family and review of the literature. Am J Med Genet A. 2013;161A(6):1414–20.

    Article  PubMed  Google Scholar 

  97. Zhang J, Li M, Yao Z. Updated review of genetic reticulate pigmentary disorders. Br J Dermatol. 2017;177(4):945–59.

    Article  CAS  PubMed  Google Scholar 

  98. Navon Elkan P, et al. Mutant adenosine deaminase 2 in a polyarteritis nodosa vasculopathy. N Engl J Med. 2014;370(10):921–31.

    Article  PubMed  CAS  Google Scholar 

  99. Beck-Engeser GB, Eilat D, Wabl M. An autoimmune disease prevented by anti-retroviral drugs. Retrovirology. 2011;8:91.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  100. Fremond ML, et al. Efficacy of the Janus kinase 1/2 inhibitor ruxolitinib in the treatment of vasculopathy associated with TMEM173-activating mutations in 3 children. J Allergy Clin Immunol. 2016;138(6):1752–5.

    Article  CAS  PubMed  Google Scholar 

  101. Manoussakis MN, et al. Type I interferonopathy in a young adult. Rheumatology (Oxford). 2017;56:2241–3.

    Article  CAS  Google Scholar 

  102. Konig N, et al. Familial chilblain lupus due to a gain-of-function mutation in STING. Ann Rheum Dis. 2017;76(2):468–72.

    Article  PubMed  CAS  Google Scholar 

  103. Jabbari A, et al. Reversal of alopecia areata following treatment with the JAK1/2 inhibitor baricitinib. EBioMedicine. 2015;2(4):351–5.

    Article  PubMed  PubMed Central  Google Scholar 

  104. Oon S, Wilson NJ, Wicks I. Targeted therapeutics in SLE: emerging strategies to modulate the interferon pathway. Clin Transl Immunol. 2016;5(5):e79.

    Article  CAS  Google Scholar 

  105. Petri M, et al. Sifalimumab, a human anti-interferon-alpha monoclonal antibody, in systemic lupus erythematosus: a phase I randomized, controlled, dose-escalation study. Arthritis Rheum. 2013;65(4):1011–21.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  106. Relle M, et al. Genetics and novel aspects of therapies in systemic lupus erythematosus. Autoimmun Rev. 2015;14(11):1005–18.

    Article  CAS  PubMed  Google Scholar 

  107. An J, et al. Cutting edge: antimalarial drugs inhibit IFN-beta production through blockade of cyclic GMP-AMP synthase-DNA interaction. J Immunol. 2015;194(9):4089–93.

    Article  CAS  PubMed  Google Scholar 

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    1. Department of Physiology, School of Medicine, National and Kapodistrian University of Athens, Athens, Greece

      Christina Maria Flessa, Evangelia Argiriou & Clio P. Mavragani

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    1. Christina Maria Flessa
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    1. New York University School of Medicine, New York, NY, USA

      Petros Efthimiou

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    Flessa, C.M., Argiriou, E., Mavragani, C.P. (2019). Type I Interferonopathies: From Pathophysiology to Clinical Expression. In: Efthimiou, P. (eds) Auto-Inflammatory Syndromes. Springer, Cham. https://doi.org/10.1007/978-3-319-96929-9_10

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