Zusammenfassung
Das phänotypische und genetische Spektrum autoinflammatorischer Erkrankungen hat in den letzten Jahren stetig zugenommen. So sind mittlerweile mehrere monogen bedingte autoinflammatorische Erkrankungen bekannt, bei denen Fieberschübe nicht im Vordergrund stehen und die neben Zeichen systemischer Entzündung auch Autoimmunphänomene oder eine pathologische Infektanfälligkeit aufweisen. Für autoinflammatorische Erkrankungen, die mit einer unkontrollierten Aktivität der Zytokine, IL-1β, TNF-α oder Typ-1-IFN einhergehen, stehen kausale Therapien zur Verfügung. Daher kommt der Sicherung der genetischen Diagnose eine große Rolle zu. Die molekulargenetische Abklärung eines Patienten mit Autoinflammation sollte in Abhängigkeit von der Symptomkonstellation stufenweise erfolgen. Bei eindeutigen Symptomen kann als Erstes die Einzelgensequenzierung erfolgen. NGS-basierte Methoden wie die Panelsequenzierung und die Exomsequenzierung sowie die Array-CGH sind bei unklarer Symptomatik sinnvoll.
Abstract
Over the past years the phenotypic and genetic spectrum of autoinflammatory diseases has continuously increased. Moreover, several monogenic autoinflammatory disorders have now been identified where febrile episodes are not among the leading symptoms and which can be accompanied by autoimmune phenomena and susceptibility to infections. Autoinflammatory conditions that are characterized by uncontrolled activity of cytokines, such as interleukin-1 beta (IL1β), tumor necrosis factor alpha (TNF-α) and type 1 interferons (1-IFN), are amenable to specific therapeutic interventions. Thus, identification of the underlying genetic cause is important. During diagnostic work-up, genetic testing of a patient with autoinflammation should be carried out depending on the clinical presentation. If a distinct disorder is suspected, sequencing of the causative gene should be performed. Genetic tests using next generation sequencing (NGS), such as panel sequencing, exome sequencing and array comparative genomic hybridization (CGH) can be carried out if symptoms cannot be assigned to a specific disease entity.
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Abbreviations
- Bp:
-
Base pairs
- CGH:
-
Comparative genomic hybridization
- IL-1β:
-
Interleukin-1β
- Kb:
-
Kilobase
- 1 kb:
-
1000 bp
- Mb:
-
Megabase
- 1 Mb:
-
1.000.000 bp
- MLPA:
-
Multiplex ligation-dependent probe amplification
- NGS:
-
Next generation sequencing
- PCR:
-
Polymerase chain reaction
- TNF-α:
-
Tumor necrosis factor-α
- Typ-1-IFN:
-
Typ-1-Interferon
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M. Bienias, N. König, C. Wolf, S. Kretschmer, A. Rösen-Wolff, R. Berner, V. Tüngler und M.A. Lee-Kirsch geben an, dass kein Interessenkonflikt besteht.
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Bienias, M., König, N., Wolf, C. et al. Genetische Methoden für die Analyse autoinflammatorischer Erkrankungen. Z Rheumatol 76, 295–302 (2017). https://doi.org/10.1007/s00393-017-0300-x
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DOI: https://doi.org/10.1007/s00393-017-0300-x