Typ-1-Interferonopathien

V. Tüngler; M. Lee-Kirsch

doi:10.1055/s-0037-1617993

Arthritis und Rheuma, Table of Contents

Arthritis und Rheuma 2014; 34(04): 225-233
DOI: 10.1055/s-0037-1617993

Kinderrheumatologie: Übersichtsarbeit

Schattauer GmbH

Typ-1-Interferonopathien

Type 1 interferonopathies

Authors

V. Tüngler

¹Molekulare Pädiatrie, Klinik für Kinder- und Jugendmedizin, Medizinische Fakultät Carl Gustav Carus, Technische Universität Dresden
M. Lee-Kirsch

¹Molekulare Pädiatrie, Klinik für Kinder- und Jugendmedizin, Medizinische Fakultät Carl Gustav Carus, Technische Universität Dresden

Abstract

Zusammenfassung

Die Aufklärung der genetischen Ursachen des Aicardi-Goutières-Syndroms und des familiären Chilblain-Lupus hat zur Identifizierung neuer pathophysiologischer Mechanismen beigetragen, die primär über das angeborene Immunsystem vermittelt werden und zu Autoinflammation und Autoimmunität führen. Diese als Typ-1-Interferonopathien bezeichneten seltenen Erkrankungen sind durch eine Dysregulation der Typ-1-Interferon (IFN)-Achse gekennzeichnet, die in einer inadäquaten Typ-1-IFN-Aktivierung resultiert. Die bisher gewonnenen Einblicke in die molekulare Pathogenese der Typ-1-Interferonopathien haben auch hohe Relevanz für unser Verständnis multifaktoriell bedingter Autoimmunkrankheiten wie dem systemischen Lupus erythematodes und können als Ausgangspunkt für die Entwicklung neuer kausal orientierter Therapieansätze dienen.

Summary

The elucidation of the genetic causes underlying the rare monogenic disorders Aicardi-Goutières syndrome and familial chilblain lupus has revealed novel disease mechanisms causing autoinflammation and autoimmunity. These so-called type 1 interferonopathies are characterized by a dysregulation of the type 1-IFN axis, which results in an inadequate type 1-IFN activation. Our current understanding of the molecular pathogenesis of type 1 interferonopathies is also highly relevant to our understanding of multifactorial autoimmune diseases such as systemic lupus erythematosus and can serve as a starting point for the development of novel causally oriented therapeutic approaches.

Schlüsselwörter

Typ-1-Interferon - Autoimmunität - Aicardi-Goutières-Syndrom - familiärer Chilblain-Lupus - systemischer Lupus erythematodes

Keywords

Type 1-interferon - autoimmunity - familial chilblain lupus - systemic lupus erythematosus

Full Text

References

Literatur
1 Crow YJ. Type I interferonopathies: a novel set of inborn errors of immunity. Ann N Y Acad Sci 2011; 1238: 91-98.
2 Nagano Y, Kojima Y. [Immunizing property of vaccinia virus inactivated by ultraviolets rays]. C R Seances Soc Biol Fil 1954; 148: 1700-1702.
3 Isaacs A, Lindenmann J. Virus interference. I. The interferon. Proc R Soc Lond B Biol Sci 1957; 147: 258-267.
4 Platanias LC. Mechanisms of type-I- and type-II-interferon-mediated signalling. Nat Rev Immunol 2005; 5: 375-386.
5 Samuel CE. Antiviral actions of interferons. Clin Microbiol Rev 2001; 14: 778-809 table
6 Lovgren T, Eloranta ML, Bave U. et al. Induction of interferon-alpha 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.
7 Marshak-Rothstein A. Toll-like receptors in systemic autoimmune disease. Nat Rev Immunol 2006; 6: 823-835.
8 Fenner JE, Starr R, Cornish AL. et al. Suppressor of cytokine signaling 1 regulates the immune response to infection by a unique inhibition of type I interferon activity. Nat Immunol 2006; 7: 33-39.
9 Richards KH, Macdonald A. Putting the brakes on the anti-viral response: negative regulators of type I interferon (IFN) production. Microbes Infect 2011; 13: 291-302.
10 Atianand MK, Fitzgerald KA. Molecular basis of DNA recognition in the immune system. J Immunol 2013; 190: 1911-1918.
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: 49-54.
12 Ramantani G, Maillard LG, Bast T. et al. Epilepsy in Aicardi-Goutieres syndrome. Eur J Paediatr Neurol 2014; 18: 30-37.
13 Lebon P, Badoual J, Ponsot G. et al. Intrathecal synthesis of interferon-alpha in infants with progressive familial encephalopathy. J Neurol Sci 1988; 84: 201-208.
14 Rice G, Patrick T, Parmar R. et al. Clinical and molecular phenotype of Aicardi-Goutieres syndrome. Am J Hum Genet 2007; 81: 713-725.
15 Ramantani G, Kohlhase J, Hertzberg C. et al. Expanding the phenotypic spectrum of lupus erythematosus in Aicardi-Goutieres syndrome. Arthritis Rheum 2010; 62: 1469-1477.
16 Vogt J, Agrawal S, Ibrahim Z. et al. Striking intrafamilial phenotypic variability in Aicardi-Goutieres syndrome associated with the recurrent Asian founder mutation in RNASEH2C. Am J Med Genet A 2013; 161A: 338-342
17 Tüngler V, Schmidt F, Hieronimus S. et al. Phenotypic Variability in a Family with Aicardi-Goutières Syndrome Due to the Common A177T RNASEH2B Mutation. Case Reports in Clinical Medicine 2014; 3: 153-156.
18 Tolmie JL, Shillito P, Hughes-Benzie R. et al. The Aicardi-Goutieres syndrome (familial, early onset encephalopathy with calcifications of the basal ganglia and chronic cerebrospinal fluid lymphocytosis). J Med Genet 1995; 32: 881-884.
19 Ramantani G, Hausler M, Niggemann P. et al. Aicardi-Goutieres syndrome and systemic lupus erythematosus (SLE) in a 12-year-old boy with SAMHD1 mutations. J Child Neurol 2011; 26: 1425-1428.
20 Rice GI, Forte GM, Szynkiewicz M. et al. Assessment of interferon-related biomarkers in Aicardi-Goutieres syndrome associated with mutations in TREX1, RNASEH2A, RNASEH2B, RNASEH2C, SAMHD1, and ADAR: a case-control study. Lancet Neurol 2013; 12: 1159-1169.
21 Akwa Y, Hassett DE, Eloranta ML. 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: 5016-5026.
22 Cuadrado E, Jansen MH, Anink J. et al. Chronic exposure of astrocytes to interferon-alpha reveals molecular changes related to Aicardi-Goutieres syndrome. Brain 2013; 136: 245-258.
23 Hoss M, Robins P, Naven TJ. et al. A human DNA editing enzyme homologous to the Escherichia coli DnaQ/MutD protein. EMBO J 1999; 18: 3868-3875.
24 Mazur DJ, Perrino FW. Identification and expression of the TREX1 and TREX2 cDNA sequences encoding mammalian 3’→5’ exonucleases. J Biol Chem 1999; 274: 19655-19660.
25 Chowdhury D, Beresford PJ, Zhu P. et al. The exonuclease TREX1 is in the SET complex and acts in concert with NM23-H1 to degrade DNA during granzyme A-mediated cell death. Mol Cell 2006; 23: 133-142.
26 Yang YG, Lindahl T, Barnes DE. Trex1 exonuclease degrades ssDNA to prevent chronic checkpoint activation and autoimmune disease. Cell 2007; 131: 873-886.
27 Stetson DB, Ko JS, Heidmann T. et al. Trex1 prevents cell-intrinsic initiation of autoimmunity. Cell 2008; 134: 587-598.
28 Deininger PL, Moran JV, Batzer MA. et al. Mobile elements and mammalian genome evolution. Curr Opin Genet Dev 2003; 13: 651-658.
29 Morita M, Stamp G, Robins P. et al. Gene-targeted mice lacking the Trex1 (DNase III) 3’→5’ DNA exonuclease develop inflammatory myocarditis. Mol Cell Biol 2004; 24: 6719-6727.
30 Gall A, Treuting P, Elkon KB. et al. Autoimmunity initiates in nonhematopoietic cells and progresses via lymphocytes in an interferon-dependent autoimmune disease. Immunity 2012; 36: 120-131.
31 Crow YJ, Hayward BE, Parmar R. et al. Mutations in the gene encoding the 3’-5’ DNA exonuclease TREX1 cause Aicardi-Goutieres syndrome at the AGS1 locus. Nat Genet 2006; 38: 917-920.
32 Rice G, Newman WG, Dean J. et al. Heterozygous Mutations in TREX1 Cause Familial Chilblain Lupus and Dominant Aicardi-Goutieres Syndrome. Am J Hum Genet 2007; 80: 811-815.
33 Tungler V, Silver RM, Walkenhorst H. et al. Inherited or de novo mutation affecting aspartate 18 of TREX1 results in either familial chilblain lupus or Aicardi-Goutieres syndrome. Br J Dermatol 2012; 167: 212-214.
34 Chon H, Vassilev A, DePamphilis ML. et al. Contributions of the two accessory subunits, RNASEH2B and RNASEH2C, to the activity and properties of the human RNase H2 complex. Nucleic Acids Res 2009; 37: 96-110.
35 Crow YJ, Leitch A, Hayward BE. et al. Mutations in genes encoding ribonuclease H2 subunits cause Aicardi-Goutieres syndrome and mimic congenital viral brain infection. Nat Genet 2006; 38: 910-916.
36 Reijns MA, Rabe B, Rigby RE. et al. Enzymatic removal of ribonucleotides from DNA is essential for mammalian genome integrity and development. Cell 2012; 149: 1008-1022.
37 Kind B, Muster B, Staroske W. et al. Altered spatio-temporal dynamics of RNase H2 complex assembly at replication and repair sites in Aicardi-Goutières syndrome. Hum Mol Genet. 2014 doi: [Epub ahead of print]
38 Goldstone DC, Ennis-Adeniran V, Hedden JJ. et al. HIV-1 restriction factor SAMHD1 is a deoxynucleoside triphosphate triphosphohydrolase. Nature 2011; 480: 379-382.
39 Rice GI, Bond J, Asipu A. et al. Mutations involved in Aicardi-Goutieres syndrome implicate SAMHD1 as regulator of the innate immune response. Nat Genet 2009; 4: 829-832.
40 Lahouassa H, Daddacha W, Hofmann H. et al. SAMHD1 restricts the replication of human immunodeficiency virus type 1 by depleting the intracellular pool of deoxynucleoside triphosphates. Nat Immunol 2012; 13: 223-228.
41 Tungler V, Staroske W, Kind B. et al. Single-stranded nucleic acids promote SAMHD1 complex formation. J Mol Med (Berl) 2013; 91: 759-770.
42 Beloglazova N, Flick R, Tchigvintsev A. et al. Nuclease activity of the human SAMHD1 protein implicated in the Aicardi-Goutieres syndrome and HIV-1 restriction. J Biol Chem 2013; 288: 8101-8110.
43 Cribier A, Descours B, Valadao AL. et al. Phosphorylation of SAMHD1 by cyclin A2/CDK1 regulates its restriction activity toward HIV-1. Cell Rep 2013; 3: 1036-1043.
44 Kretschmer S, Wolf C, Konig N. et al. SAMHD1 prevents autoimmunity by maintaining genome stability. Ann Rheum Dis. 2014 doi: [Epub ahead of print]
45 Rice GI, Kasher PR, Forte GM. et al. Mutations in ADAR1 cause Aicardi-Goutieres syndrome associated with a type I interferon signature. Nat Genet 2012; 44: 1243-1248.
46 Hartner JC, Walkley CR, Lu J. et al. ADAR1 is essential for the maintenance of hematopoiesis and suppression of interferon signaling. Nat Immunol 2009; 10: 109-115.
47 Rice GI, Del Toro DY, Jenkinson EM. et al. Gain-of-function mutations in IFIH1 cause a spectrum of human disease phenotypes associated with upregulated type I interferon signaling. Nat Genet 2014; 46: 503-509.
48 Richards A, van den Maagdenberg AM, Jen JC. et al. C-terminal truncations in human 3’-5’ DNA exonuclease TREX1 cause autosomal dominant retinal vasculopathy with cerebral leukodystrophy. Nat Genet 2007; 39: 1068-1070.
49 Lee-Kirsch MA, Gong M, Schulz H. et al. Familial chilblain lupus, a monogenic form of cutaneous lupus erythematosus, maps to chromosome 3p. Am J Hum Genet 2006; 79: 731-737.
50 Gunther C, Meurer M, Stein A. et al. Familial chilblain lupus--a monogenic form of cutaneous lupus erythematosus due to a heterozygous mutation in TREX1. Dermatology 2009; 219: 162-166.
51 Gunther C, Hillebrand M, Brunk J. et al. Systemic involvement in TREX1-associated familial chilblain lupus. J Am Acad Dermatol 2013; 69: e179-e181.
52 Lee-Kirsch MA, Chowdhury D, Harvey S. et al. A mutation in TREX1 that impairs susceptibility to granzyme A-mediated cell death underlies familial chilblain lupus. J Mol Med 2007; 85: 531-537.
53 Dale RC, Gornall H, Singh-Grewal D. et al. Familial Aicardi-Goutieres syndrome due to SAMHD1 mutations is associated with chronic arthropathy and contractures. Am J Med Genet A 2010; 152A: 938-942
54 Renella R, Schaefer E, LeMerrer M. 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: 541-550.
55 Briggs TA, Rice GI, Daly S. et al. Tartrate-resistant acid phosphatase deficiency causes a bone dysplasia with autoimmunity and a type I interferon expression signature. Nat Genet 2011; 43: 127-131.
56 Lausch E, Janecke A, Bros M. et al. Genetic deficiency of tartrate-resistant acid phosphatase associated with skeletal dysplasia, cerebral calcifications and autoimmunity. Nat Genet 2011; 43: 132-137.
57 Harley IT, Kaufman KM, Langefeld CD. et al. Genetic susceptibility to SLE: new insights from fine mapping and genome-wide association studies. Nat Rev Genet 2009; 10: 285-290.
58 Hooks JJ, Moutsopoulos HM, Geis SA. et al. Immune interferon in the circulation of patients with autoimmune disease. N Engl J Med 1979; 301: 5-8.
59 Baechler EC, Batliwalla FM, Karypis G. et al. Interferon-inducible gene expression signature in peripheral blood cells of patients with severe lupus. Proc Natl Acad Sci U S A 2003; 100: 2610-2615.
60 Niewold TB, Hua J, Lehman TJ. et al. High serum IFN-alpha activity is a heritable risk factor for systemic lupus erythematosus. Genes Immun 2007; 8: 492-502.
61 Blanco P, Palucka AK, Gill M. et al. Induction of dendritic cell differentiation by IFN-alpha in systemic lupus erythematosus. Science 2001; 294: 1540-1543.
62 Niewold TB. Interferon alpha-induced lupus: proof of principle. J Clin Rheumatol 2008; 14: 131-132.
63 Lee-Kirsch MA, Gong M, Chowdhury D. et al. Mutations in the gene encoding the 3’-5’ DNA exonuclease TREX1 are associated with systemic lupus erythematosus. Nat Genet 2007; 39: 1065-1067.
64 Yasutomo K, Horiuchi T, Kagami S. et al. Mutation of DNASE1 in people with systemic lupus erythematosus. Nat Genet 2001; 28: 313-314.
65 Al-Mayouf SM, Sunker A, Abdwani R. et al. Loss-of-function variant in DNASE1L3 causes a familial form of systemic lupus erythematosus. Nat Genet 2011; 43: 1186-1188.
66 Manderson AP, Botto M, Walport MJ. The role of complement in the development of systemic lupus erythematosus. Annu Rev Immunol 2004; 22: 431-456.
67 Santer DM, Hall BE, George TC. et al. C1q deficiency leads to the defective suppression of IFN-alpha in response to nucleoprotein containing immune complexes. J Immunol 2010; 185: 4738-4749.
68 Chatterjee P, Agyemang AF, Alimzhanov MB. et al. Complement C4 maintains peripheral B-cell tolerance in a myeloid cell dependent manner. Eur J Immunol 2013; 43: 2441-2450.
69 Lee-Kirsch MA, Wolf C, Gunther C. Aicardi-Goutieres syndrome: a model disease for systemic autoimmunity. Clin Exp Immunol 2014; 175: 17-24.
70 Behrendt R, Roers A. Mouse models for Aicardi-Goutieres syndrome provide clues to the molecular pathogenesis of systemic autoimmunity. Clin Exp Immunol 2014; 175: 9-16.
71 Yao Y, Richman L, Higgs BW. et al. Neutralization of interferon-alpha/beta-inducible genes and downstream effect in a phase I trial of an anti-interferon-alpha monoclonal antibody in systemic lupus erythematosus. Arthritis Rheum 2009; 60: 1785-1796.
72 Petri M, Wallace DJ, Spindler A. 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: 1011-1021.
73 Beck-Engeser GB, Eilat D, Wabl M. An autoimmune disease prevented by anti-retroviral drugs. Retrovirology 2011; 8: 91.
74 Volkman HE, Stetson DB. The enemy within: endogenous retroelements and autoimmune disease. Nat Immunol 2014; 15: 415-422.