Monogenic Autoinflammatory Diseases: State of the Art and Future Perspectives
Systemic autoinflammatory diseases are a heterogeneous family of disorders characterized by a dysregulation of the innate immune system, in which sterile inflammation primarily develops through antigen-independent hyperactivation of immune pathways. In most cases, they have a strong genetic backgrou...
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| Format: | Article |
| Language: | English |
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MDPI AG
2021-06-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/22/12/6360 |
| _version_ | 1797530165907030016 |
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| author | Giulia Di Donato Debora Mariarita d’Angelo Luciana Breda Francesco Chiarelli |
| author_facet | Giulia Di Donato Debora Mariarita d’Angelo Luciana Breda Francesco Chiarelli |
| author_sort | Giulia Di Donato |
| collection | DOAJ |
| description | Systemic autoinflammatory diseases are a heterogeneous family of disorders characterized by a dysregulation of the innate immune system, in which sterile inflammation primarily develops through antigen-independent hyperactivation of immune pathways. In most cases, they have a strong genetic background, with mutations in single genes involved in inflammation. Therefore, they can derive from different pathogenic mechanisms at any level, such as dysregulated inflammasome-mediated production of cytokines, intracellular stress, defective regulatory pathways, altered protein folding, enhanced NF-kappaB signalling, ubiquitination disorders, interferon pathway upregulation and complement activation. Since the discover of pathogenic mutations of the pyrin-encoding gene MEFV in Familial Mediterranean Fever, more than 50 monogenic autoinflammatory diseases have been discovered thanks to the advances in genetic sequencing: the advent of new genetic analysis techniques and the discovery of genes involved in autoinflammatory diseases have allowed a better understanding of the underlying innate immunologic pathways and pathogenetic mechanisms, thus opening new perspectives in targeted therapies. Moreover, this field of research has become of great interest, since more than a hundred clinical trials for autoinflammatory diseases are currently active or recently concluded, allowing us to hope for considerable acquisitions for the next few years. General paediatricians need to be aware of the importance of this group of diseases and they should consider autoinflammatory diseases in patients with clinical hallmarks, in order to guide further examinations and refer the patient to a specialist rheumatologist. Here we resume the pathogenesis, clinical aspects and diagnosis of the most important autoinflammatory diseases in children. |
| first_indexed | 2024-03-10T10:25:07Z |
| format | Article |
| id | doaj.art-1ab934bb7095463fb718881a15f77cdb |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-10T10:25:07Z |
| publishDate | 2021-06-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-1ab934bb7095463fb718881a15f77cdb2023-11-22T00:03:33ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672021-06-012212636010.3390/ijms22126360Monogenic Autoinflammatory Diseases: State of the Art and Future PerspectivesGiulia Di Donato0Debora Mariarita d’Angelo1Luciana Breda2Francesco Chiarelli3Department of Pediatrics, University of Chieti, 66100 Chieti, ItalyDepartment of Pediatrics, University of Chieti, 66100 Chieti, ItalyDepartment of Pediatrics, University of Chieti, 66100 Chieti, ItalyDepartment of Pediatrics, University of Chieti, 66100 Chieti, ItalySystemic autoinflammatory diseases are a heterogeneous family of disorders characterized by a dysregulation of the innate immune system, in which sterile inflammation primarily develops through antigen-independent hyperactivation of immune pathways. In most cases, they have a strong genetic background, with mutations in single genes involved in inflammation. Therefore, they can derive from different pathogenic mechanisms at any level, such as dysregulated inflammasome-mediated production of cytokines, intracellular stress, defective regulatory pathways, altered protein folding, enhanced NF-kappaB signalling, ubiquitination disorders, interferon pathway upregulation and complement activation. Since the discover of pathogenic mutations of the pyrin-encoding gene MEFV in Familial Mediterranean Fever, more than 50 monogenic autoinflammatory diseases have been discovered thanks to the advances in genetic sequencing: the advent of new genetic analysis techniques and the discovery of genes involved in autoinflammatory diseases have allowed a better understanding of the underlying innate immunologic pathways and pathogenetic mechanisms, thus opening new perspectives in targeted therapies. Moreover, this field of research has become of great interest, since more than a hundred clinical trials for autoinflammatory diseases are currently active or recently concluded, allowing us to hope for considerable acquisitions for the next few years. General paediatricians need to be aware of the importance of this group of diseases and they should consider autoinflammatory diseases in patients with clinical hallmarks, in order to guide further examinations and refer the patient to a specialist rheumatologist. Here we resume the pathogenesis, clinical aspects and diagnosis of the most important autoinflammatory diseases in children.https://www.mdpi.com/1422-0067/22/12/6360systemic autoinflammatory diseasesinflammasomopathiesinterferonopathiesperiodic fevernext generation sequencing |
| spellingShingle | Giulia Di Donato Debora Mariarita d’Angelo Luciana Breda Francesco Chiarelli Monogenic Autoinflammatory Diseases: State of the Art and Future Perspectives International Journal of Molecular Sciences systemic autoinflammatory diseases inflammasomopathies interferonopathies periodic fever next generation sequencing |
| title | Monogenic Autoinflammatory Diseases: State of the Art and Future Perspectives |
| title_full | Monogenic Autoinflammatory Diseases: State of the Art and Future Perspectives |
| title_fullStr | Monogenic Autoinflammatory Diseases: State of the Art and Future Perspectives |
| title_full_unstemmed | Monogenic Autoinflammatory Diseases: State of the Art and Future Perspectives |
| title_short | Monogenic Autoinflammatory Diseases: State of the Art and Future Perspectives |
| title_sort | monogenic autoinflammatory diseases state of the art and future perspectives |
| topic | systemic autoinflammatory diseases inflammasomopathies interferonopathies periodic fever next generation sequencing |
| url | https://www.mdpi.com/1422-0067/22/12/6360 |
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