Subscribe to RSS
DOI: 10.1055/a-1849-5251
Typ-1-Interferonopathien
Ein ÜberblickType 1 interferonopathiesAn overviewZUSAMMENFASSUNG
Die Typ-1-Interferonopathien umfassen eine Gruppe seltener, genetisch und phänotypisch heterogener Erkrankungen, die durch eine chronische Typ-1-IFN-Aktivierung gekennzeichnet sind und denen eine Fehlfunktion des angeborenen Immunsystems zugrunde liegt. Das breite und variable klinische Spektrum ist durch das gemeinsame Auftreten von Autoinflammation und Autoimmunität, aber auch einer möglichen Immundefizienz charakterisiert. Ursächlich sind meist Störungen im Metabolismus oder Sensing von Nukleinsäuren, welche zu einer pathologischen, konstitutiven Aktivierung der Typ-1-IFN-Achse mit schädlichen Folgen für den Wirtsorganismus führen. Januskinase-Inhibitoren können eine effektive Therapieoption darstellen.
ABSTRACT
The type 1 interferonopathies comprise a group of rare, genetically and phenotypically heterogeneous diseases characterized by a constitutive activation of type I interferon that is caused by a dysfunction of the innate immune system. The broad and variable clinical spectrum is characterized by the co-occurrence of autoinflammation, autoimmunity and immunodeficiency. Most commonly, pertubations in the metabolism or sensing of nucleic acids are responsible for the pathological constitutive activation of the type I IFN axis with harmful consequences for the host organism. Janus kinase inhibitors may provide an effective therapeutical option.
Schlüsselwörter
Typ-1-Interferon - angeborene Immunität - Autoinflammation - Autoimmunität - GenetikPublication History
Article published online:
07 September 2022
© 2022. Thieme. All rights reserved.
Georg Thieme Verlag KG
Rüdigerstraße 14, 70469 Stuttgart, Germany
-
Literatur
- 1 Isaacs A, Lindenmann J. Virus interference. I. The interferon. Proc R Soc Lond B Biol Sci 1957; 147: 258-267 DOI: 10.1098/rspb.1957.0048.
- 2 Teijaro JR. Type I interferons in viral control and immune regulation. Curr Opin Virol 2016; 16: 31-40 DOI: 10.1016/j.coviro.2016.01.001.
- 3 Janeway CA, Medzhitov R. Innate immune recognition. Annu Rev Immunol 2002; 20: 197-216 DOI: 10.1146/annurev.immunol.20.083001.084359.
- 4 O’Neill LAJ, Golenbock D, Bowie AG. The history of Toll-like receptors –redefining innate immunity. Nat Rev Immunol 2013; 13: 453-460 DOI: 10.1038/nri3446.
- 5 Ishikawa H, Ma Z, Barber GN. STING regulates intracellular DNA-mediated, type I interferon-dependent innate immunity. Nature 2009; 461: 788-792 DOI: 10.1038/nature08476.
- 6 Kato H, Takeuchi O, Sato S. et al Differential roles of MDA5 and RIG-I helicases in the recognition of RNA viruses. Nature 2006; 441: 101-105 DOI: 10.1038/nature04734.
- 7 Pichlmair A, Schulz O, Tan CP. et al RIG-I-Mediated Antiviral Responses to Single-Stranded RNA Bearing 5’-Phosphates. Science 2006; 314: 997-1001 DOI: 10.1126/science.1132998.
- 8 Hornung V, Ellegast J, Kim S. et al 5’-Triphosphate RNA Is the Ligand for RIG-I. Science 2006; 314: 994-997 DOI: 10.1126/science.1132505.
- 9 Darnell JE, Kerr lan M, Stark GR. Jak-STAT Pathways and Transcriptional Activation in Response to IFNs and Other Extracellular Signaling Proteins. Science 1994; 264: 1415-1421 DOI: 10.1126/science.8197455.
- 10 Leonard WJ, O’Shea JJ. Jaks and STATs: biological implications. Annu Rev Immunol 1998; 16: 293-322 DOI: 10.1146/annurev.immunol.16.1.293.
- 11 Lee-Kirsch MA. The Type I Interferonopathies. Annu Rev Med 2017; 68: 297-315 DOI: 10.1146/annurev-med-050715-104506.
- 12 König N, Fiehn C, Wolf C. et al Familial chilblain lupus due to a gain-of-function mutation in STING. Ann Rheum Dis 2017; 76: 468-472 DOI: 10.1136/annrheumdis-2016-209841.
- 13 Kretschmer S, Wolf C, König N. et al SAMHD1 prevents autoimmunity by maintaining genome stability. Ann Rheum Dis 2015; 74: e17 DOI: 10.1136/annrheumdis-2013-204845.
- 14 Crow YJ, Stetson DB. The type I interferonopathies: 10 years on. Nat Rev Immunol 2021 DOI: 10.1038/s41577-021-00633-9
- 15 Manthiram K, Zhou Q, Aksentijevich I. et al The monogenic autoinflammatory diseases define new pathways in human innate immunity and inflammation. Nat Immunol 2017; 18: 832-842 DOI: 10.1038/ni.3777.
- 16 Liu Y, Jesus AA, Marrero B. et al Activated STING in a vascular and pulmonary syndrome. N Engl J Med 2014; 371: 507-518 DOI: 10.1056/NEJMoa1312625.
- 17 Seo J, Kang J-A, Suh DI. et al Tofacitinib relieves symptoms of stimulator of interferon genes (STING)–associated vasculopathy with onset in infancy caused by 2 de novo variants in TMEM173. J Allergy Clin Immunol 2017; 139: 1396-1399.e12 DOI: 10.1016/j.jaci.2016.10.030.
- 18 Sanchez GAM, Reinhardt A, Ramsey S. et al JAK1/2 inhibition with baricitinib in the treatment of autoinflammatory interferonopathies. J Clin Invest 2018; 128: 3041-3052 DOI: 10.1172/JCI98814.
- 19 Vanderver A, Adang L, Gavazzi F. et al Janus Kinase Inhibition in the Aicardi-Goutières Syndrome. N Engl J Med 2020; 383: 986-989 DOI: 10.1056/NEJMc2001362.
- 20 Kim H, Brooks KM, Tang CC. et al Pharmacokinetics, Pharmacodynamics, and Proposed Dosing of the Oral JAK1 and JAK2 Inhibitor Baricitinib in Pediatric and Young Adult CANDLE and SAVI Patients. Clin Pharmacol Ther 2018; 104: 364-373 DOI: 10.1002/cpt.936.
- 21 Rice GI, Forte GMA, Szynkiewicz M. et al Assessment of interferon-related biomarkers in Aicardi-Goutières syndrome associated with mutations in TREX1, RNASEH2A, RNASEH2B, RNASEH2C, SAMHD1, and ADAR: a case-control study. Lancet Neurol 2013; 12: 1159-1169 DOI: 10.1016/S1474-4422(13)70258-8.
- 22 Takeuchi T, Tanaka Y, Matsumura R. et al Safety and tolerability of sifalimumab, an anti-interferon-α monoclonal antibody, in Japanese patients with systemic lupus erythematosus: A multicenter, phase 2, open-label study. Mod Rheumatol 2020; 30: 93-100 DOI: 10.1080/14397595.2019.1583832.
- 23 Morand EF, Furie R, Tanaka Y. et al Trial of Anifrolumab in Active Systemic Lupus Erythematosus. N Engl J Med 2020; 382: 211-221 DOI: 10.1056/NEJMoa1912196.
- 24 d’Angelo DM, Di Filippo P, Breda L. et al Type I Interferonopathies in Children: An Overview. Front Pediatr 2021: 9