Case Report: Genetic Double Strike: VEXAS and TET2-Positive Myelodysplastic Syndrome in a Patient With Long-Standing Refractory Autoinflammatory Disease

被引:25
作者
Loetscher, Fabian [1 ]
Seitz, Luca [1 ]
Simeunovic, Helena [2 ]
Sarbu, Adela-Cristina [1 ]
Porret, Naomi A. [2 ]
Feldmeyer, Laurence [3 ]
Borradori, Luca [3 ]
Bonadies, Nicolas [2 ,4 ]
Maurer, Britta [1 ]
机构
[1] Univ Bern, Bern Univ Hosp, Inselspital, Dept Rheumatol & Immunol, Bern, Switzerland
[2] Univ Bern, Inselspital Bern, Dept Hematol & Cent Hematol Lab, Bern, Switzerland
[3] Univ Bern, Bern Univ Hosp, Inselspital, Dept Dermatol, Bern, Switzerland
[4] Univ Bern, Dept BioMed Res, Bern, Switzerland
来源
FRONTIERS IN IMMUNOLOGY | 2022年 / 12卷
关键词
VEXAS syndrome; autoinflammation; TET2; vasculitis; MDS; CHRONIC MYELOMONOCYTIC LEUKEMIA; CLONAL HEMATOPOIESIS; MANIFESTATIONS; CLASSIFICATION; INFLAMMATION; CRITERIA;
D O I
10.3389/fimmu.2021.800149
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Somatic genetic mutations involving the innate and inflammasome signaling are key drivers of the pathogenesis of myelodysplastic syndromes (MDS). Herein, we present a patient, who suffered from a long-standing refractory adult-onset autoinflammatory syndrome (AIS), previously interpreted as various distinct rheumatic disorders. Developing pancytopenia and particularly macrocytic anemia prompted the screening for a hematological malignancy, which led to the diagnosis of a TET-2-positive MDS. The impressive and continuously changing range of organ involvement, with remarkable refractoriness to anti-inflammatory treatment, exceeded the common autoinflammatory phenotype of MDS patients. This prompted us to suspect a recently discovered disease, characterized by somatic mutations of the UBA1 gene: the VEXAS (Vacuoles, E1 enzyme, X-linked, Autoinflammatory, Somatic) syndrome, which was ultimately confirmed by genetic testing. Reevaluation of previous bone marrow biopsies showed the presence of characteristic vacuoles in myeloid- and erythroid progenitor cells. Our case illustrates that the triad of an unresponsive multisystemic autoinflammatory disease, hematological abnormalities and vacuoles in myeloid- and erythroid progenitors in the bone marrow biopsy should prompt screening for the VEXAS syndrome.
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页数:7
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