Problemi speciali
Le interferonopatie di tipo I
Type I interferonopathies
Alberto Tommasini1,2, Irene Bruno1, Maria Elisa Morelli3, Loredana Lepore1
1Clinica Pediatrica, IRCCS Materno-Infantile “Burlo Garofolo”, Trieste
2Dipartimento di Scienze Mediche, Chirurgiche e della Salute, Università di Trieste
3SC di Neuropsichiatria Infantile, IRCCS Materno-Infantile “Burlo Garofolo”, Trieste
Ottobre 2021 - pagg. 509 -514 | DOI: 10.53126/MEB40509
Abstract
Type I interferonopathies are autoinflammatory monogenic disorders arising from excessive production of interferons. Some manifestations like chilblains, neurologic involvement, arthritis and lipodystrophy may be shared by several diseases. Measure of interferon score and genetic analysis can assist a definite diagnosis. Among immunomodulant drugs, glucocorticoids, micofenolate and antimalarials can be of some benefit, however other drugs like JAK inhibitors seem more effective in controlling interferon-related complaints. Apart from allowing better diagnosis and care to affected patients, the study of interferonopathies may also reflect on a better knowledge on multifactorial disorders associated with interferon-related inflammation.
Riassunto
Le interferonopatie di tipo 1 sono un gruppo di malattie autoinfiammatorie monogeniche caratterizzate da eccessiva produzione di interferoni di tipo I. Alcuni sintomi, come il lupus pernio, il coinvolgimento neurologico, l’artrite e la lipodistrofia possono caratterizzare diverse interferonopatie. La diagnosi si basa sulla misura dello score interferonico e su esami genetici. Tra i farmaci immunomodulatori convenzionali, solo i glucocorticoidi, il micofenolato e gli antimalarici sembrano di qualche utilità, mentre appaiono più promettenti i JAK-inibitori, in grado di inibire meglio gli effetti interferonici. Lo studio di queste malattie, oltre a permettere una migliore diagnosi e cura per i bambini affetti, comporta anche su una migliore comprensione di malattie multifattoriali più comuni, come il lupus eritematoso sistemico, la dermatomiosite o la malattia di Sjögren, in cui l’infiammazione interferonica può giocare un ruolo di primo piano.
Classificazione MeSH
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Bibliografia
1. Tommasini A, Lepore L. Le sindromi autoinfiammatorie: quando non è solo PFAPA
Medico e Bambino 2021;40(4):221-5. doi: 10.53126/MEB402211.
2. Volpi S, Picco P, Caorsi R, Candotti F, Gattorno M. Type I interferonopathies in pediatric rheumatology. Pediatr Rheumatol Online J 2016;14:35. doi: 10.1186/s12969-016-0094-4.
3. Volpi, S, Tommasini, A. Le interferonopatie. Prospettive in Pediatria 2020;50:65-75.
4. Ablasser A, Hur S. Regulation of cGAS- and RLR-mediated immunity to nucleic acids. Nat Immunol 2020;21:17-29. doi: 10.1038/ s41590-019-0556-1.
5. Horvath CM. The Jak-STAT pathway stimulated by interferon alpha or interferon beta. Sci STKE 2004;2004(260):tr10. doi: 10.1126/stke.2602004tr10.
6. Mielcarska MB, Bossowska-Nowicka M, Toka FN. Functional failure of TLR3 and its signaling components contribute to herpes simplex encephalitis. J Neuroimmunol 2018; 316:65-73. doi: 10.1016/j.jneuroim.2017. 12.011.
7. Rodero MP, Crow YJ. Type I interferon-mediated monogenic autoinflammation: the type I interferonopathies, a conceptual overview. J Exp Med 2016;213:2527-38. doi: 10.1084/jem.20161596.
8. 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. doi: 10.1007/s00109-016-1465-5.
9. 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(5):2610-5. doi: 10.1073/pnas. 0337679100.
10. Rice GI, Forte GM, 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 (12):1159-69. doi: 10.1016/S1474-4422(13) 70258-8.
11. Pin A, Monasta L, Taddio A, Piscianz E, Tommasini A, Tesser A. An easy and reliable strategy for making type I interferon signature analysis comparable among research Centers. Diagnostics (Basel) 2019;9:113. doi: 10.3390/diagnostics9030113.
12. Prencipe, G, Bracaglia, C, Caiello, I, et al. The interferon-gamma pathway is selectively up-regulated in the liver of patients with secondary hemophagocytic lymphohistiocytosis. PLoS One 2019;14:e0226043. doi: 10.1371/journal.pone.0226043.
13. Garau J, Cavallera V, Valente M, et al. Molecular genetics and interferon signature in the Italian Aicardi-Goutières syndrome cohort: report of 12 new cases and literature review. J Clin Med 2019;8(5):750. doi: 10.3390/jcm8050750.
14. Crow YJ, Chase DS, Lowenstein Schmidt J, et al. Characterization of human disease phenotypes associated with mutations in TREX1, RNASEH2A, RNASEH2B, RNASEH2C, SAMHD1, ADAR, and IFIH1. Am J Med Genet A 2015;167A(2):296-312. doi: 10.1002/ajmg.a.36887.
15. Bourgon N, Lefebvre M, Kuentz P, et al. Prenatal presentation of Aicardi-Goutières syndrome: Nonspecific phenotype necessitates exome sequencing for definitive diagnosis. Prenat Diagn 2019;39(9):806-10. doi: 10.1002/pd.5424.
16. Crow YJ, Manel N. Aicardi-Goutieres syndrome and the type I interferonopathies. Nat Rev Immunol 2015;15(7):429-40. doi: 10.1038/nri3850.
17. Mura, E, Masnada, S, Antonello, C, et al. Ruxolitinib in Aicardi-Goutières syndrome. Metab Brain Dis 2021;36(5):859-63. doi: 10.1007/s11011-021-00716-5.
18. Tonduti D, Fazzi E, Badolato R, Orcesi S. Novel and emerging treatments for Aicardi-Goutières syndrome. Expert Rev Clin Immunol 2020;16(2):189-98. doi: 10.1080/ 1744666X.2019.1707663.
19. Meesilpavikkai K, Dik WA, Schrijver B, et al. Efficacy of baricitinib in the treatment of chilblains associated with Aicardi-Goutières syndrome, a type I interferonopathy. Arthritis Rheumatol 2019;71(5):829-31. doi: 10.1002/art.40805.
20. Ohmura K. Nakajo-Nishimura syndrome and related proteasome-associated autoinflammatory syndromes. J Inflamm Res 2019; 12:259-65. doi: 10.2147/JIR.S194098.
21. McDermott A, Jacks J, Kessler M, Emanuel PD, Gao L. Proteasome-associated autoinflammatory syndromes: advances in pathogeneses, clinical presentations, diagnosis, and management. Int J Dermatol 2015; 54(2):121-9. doi: 10.1111/ijd.12695.
22. Sanchez GAM, Reinhardt A, Ramsey S, et al. JAK1/2 inhibition with baricitinib in the treatment of autoinflammatory interferonopathies. J Clin Invest 2018;128(7):3041-52. doi: 10.1172/JCI98814.
23. Liu Y, Jesus AA, Marrero B, et al. Activated STING in a vascular and pulmonary syndrome. N Engl J Med 2014;371(6):507-18. doi: 10.1056/NEJMoa1312625.
24. Frémond ML, Hadchouel A, Berteloot L, et al. Overview of STING-Associated Vasculopathy with onset in Infancy (SAVI) among 21 patients. J Allergy Clin Immunol Pract 2021;9(2):803-18.e11. doi: 10.1016/j.jaip. 2020.11.007.
25. Munoz, J, Rodiere, M, Jeremiah, N, et al. Stimulator of interferon genes-associated vasculopathy with onset in infancy: a mimic of childhood granulomatosis with polyangiitis. JAMA Dermatol 2015;151(8):872-7. doi: 10.1001/jamadermatol.2015.0251.
26. Vece TJ, Watkin LB, Nicholas S, et al. Copa syndrome: a novel autosomal dominant immune dysregulatory disease. J Clin Immunol 2016;36(4):377-87. doi: 10.1007/s10875-016-0271-8.
27. Lepelley A, Martin-Niclos MJ, Le Bihan M, et al. Mutations in COPA lead to abnormal trafficking of STING to the Golgi and interferon signaling. J Exp Med 2020;217(11): e20200600. doi: 10.1084/jem.20200600.
28. Fremond ML, Nathan N. COPA syndrome, 5 years after: where are we? Joint Bone Spine 2021;88(2):105070. doi: 10.1016/j.jbspin.2020.09.002.
29. Watkin LB, Jessen B, Wiszniewski W, et al. COPA mutations impair ER-Golgi transport and cause hereditary autoimmune-mediated lung disease and arthritis. Nat Genet 2015;47(6):654-60. doi: 10.1038/ng.3279.
30. Volpi S, Tsui J, Mariani M, et al. Type I interferon pathway activation in COPA syndrome. Clin Immunol 2018;187:33-6. doi: 10.1016/j.clim.2017.10.001.
31. Frémond ML, Legendre M, Fayon M, et al. Use of ruxolitinib in COPA syndrome manifesting as life-threatening alveolar haemorrhage. Thorax 2020;75:92-5. doi: 10.1136/thoraxjnl-2019-213892.
32. Krutzke S, Rietschel C, Horneff G. Baricitinib in therapy of COPA syndrome in a 15-year-old girl. Eur J Rheumatol 2019;7(Suppl 1):1-4. doi: 10.5152/eurjrheum.2019.18177.
33. Muskardin TLW, Niewold TB. Type I interferon in rheumatic diseases. Nat Rev Rheumatol 2018;14(4):214-28. doi: 10.1038/ nrrheum.2018.31.
34. Rönnblom L, Leonard D. Interferon pathway in SLE: one key to unlocking the mystery of the disease. Lupus Sci Med 2019;6(1):e000270. doi: 10.1136/lupus-2018-000270.
35. Niewold TB, Hua J, Lehman TJ, Harley JB, Crow MK. High serum IFN-alpha activity is a heritable risk factor for systemic lupus erythematosus. Genes Immun 2007;8:492-502. doi: 10.1038/sj.gene.6364408.
36.Landolt-Marticorena C, Bonventi G, Lubovich A, et al. Lack of association between the interferon-alpha signature and longitudinal changes in disease activity in systemic lupus erythematosus. Ann Rheum Dis 2009;68 (9):1440-6. doi: 10.1136/ard.2008. 093146.
37. Felten R, Scher F, Sagez F, Chasset F, Arnaud L. Spotlight on anifrolumab and its potential for the treatment of moderate-to-severe systemic lupus erythematosus: evidence to date. Drug Des Devel Ther 2019;13:1535-43. doi: 10.2147/DDDT.S170969.
38. Brohawn PZ, Streicher K, Higgs BW, et al. Type I interferon gene signature test-low and -high patients with systemic lupus erythematosus have distinct gene expression signatures. Lupus 2019;28(13):1524-33. doi: 10.1177/0961203319885447.
39. Rubenstein M, Shaw M, Targonski P, McKiel CF, Dubin A, Guinan P. GM-CSF restoration of a differentiated (growth factor-regulated) phenotype in an anaplastic tumor. Urol Res 1991;19(5):309-12. doi: 10.1007/ BF00299066.
40. Balboni I, Niewold TB, Morgan G, et al. Interferon-alpha induction and detection of anti-ro, anti-la, anti-sm, and anti-rnp autoantibodies by autoantigen microarray analysis in juvenile dermatomyositis. Arthritis Rheum 2013;65(9):2424-9. doi: 10.1002/art.38038.
41. Moghadam-Kia S, Charlton D, Aggarwal R, Oddis CV. Management of refractory cutaneous dermatomyositis: potential role of Janus kinase inhibition with tofacitinib. Rheumatology (Oxford) 2019;58(6):1011-5. doi: 10.1093/rheumatology/key366.
42. Ladislau L, Suarez-Calvet X, Toquet S, et al. JAK inhibitor improves type I interferon induced damage: proof of concept in dermatomyositis. Brain 2018;141(6):1609-21. doi: 10.1093/brain/awy105.
43. Chen Z, Wang X, Ye S. Tofacitinib in amyopathic dermatomyositis-associated interstitial lung disease. N Engl J Med 2019; 381(3):291-3. doi: 10.1056/NEJMc1900045.
Corrispondenza: alberto.tommasini@burlo.trieste.it