Das VEXAS-Syndrom

ZUSAMMENFASSUNG

Das VEXAS-Syndrom ist eine neu identifizierte autoinflammatorische Systemerkrankung. Dabei steht das Akronym VEXAS für Vacuoles, E1 enzyme, X-linked, Autoinflammatory, Somatic. Zugrundeliegend für die Erkrankung ist eine somatische Mutation des UBA1-Gens. Dieses kodiert für das E1-Enzym, welches für die Ubiquitinierung von Proteinen verantwortlich ist. Aufgrund der fehlerhaften Ubiquitinierung kommt es zu einer Überregulierung von proinflammatorischen Zytokinen. Da das UBA1-Gen auf dem X-Chromosom liegt, sind von der Erkrankung fast nur Männer betroffen. Interessanterweise tritt das VEXAS-Syndrom erst in der 2. Lebenshälfte auf und die Betroffenen können eine Vielzahl von inflammatorischen klinischen Symptomen aufweisen. Insbesondere das Vorliegen von zytoplasmatischen Vakuolen im Knochenmark ist charakteristisch. Hierbei kommt es in der klinischen Ausprägung häufig zu Überlappungen aus hämatologischen, dermatologischen und rheumatologischen Krankheitsbildern. Der Artikel gibt einen Überblick über die Pathophysiologie, Klinik und Diagnostik des Erkrankungsbildes.

ABSTRACT

VEXAS syndrome is a newly identified autoinflammatory systemic disease. The VEXAS acronym stands for vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic. The disease is caused by a somatic mutation of the UBA1 gene. This gene is responsible for the E1 enzyme, which is involved in the ubiquitination of proteins. Due to abnormal ubiquitination, proinflammatory cytokines are grossly upregulated. Since the UBA1 gene is located on the X chromosome, the disease affects almost only males. Interestingly, VEXAS syndrome does occur in the 2. half of life and affected individuals may present with a variety of inflammatory clinical symptoms. In particular, the presence of cytoplasmic vacuoles in the bone marrow is characteristic. The clinical manifestations often overlap between hematological, dermatological and rheumatological diseases. This article provides an overview of the pathophysiology, clinical manifestations and diagnostic features of the disease.

Schlüsselwörter

Autoinflammation - Hämatoinflammation - X-Chromosom - Vakuolen - myelodypslastisches Syndrom - Polychondritis - Ruxolitinib-Stammzelltransplantation

Keywords

Autoinflammation - hematoinflammation - X-chromosome - vacuoles - myelodysplastic syndrome - polychondritis - ruxolitinib stem cell transplantation

• Literatur

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