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Case Report: Genetic Double Strike: VEXAS and TET2-Positive Myelodysplastic Syndrome in a Patient With Long-Standing Refractory Autoinflammatory Disease
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...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Frontiers Media S.A.
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8811255/ https://www.ncbi.nlm.nih.gov/pubmed/35126364 http://dx.doi.org/10.3389/fimmu.2021.800149 |
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author | Lötscher, Fabian Seitz, Luca Simeunovic, Helena Sarbu, Adela-Cristina Porret, Naomi A. Feldmeyer, Laurence Borradori, Luca Bonadies, Nicolas Maurer, Britta |
author_facet | Lötscher, Fabian Seitz, Luca Simeunovic, Helena Sarbu, Adela-Cristina Porret, Naomi A. Feldmeyer, Laurence Borradori, Luca Bonadies, Nicolas Maurer, Britta |
author_sort | Lötscher, Fabian |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-8811255 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-88112552022-02-04 Case Report: Genetic Double Strike: VEXAS and TET2-Positive Myelodysplastic Syndrome in a Patient With Long-Standing Refractory Autoinflammatory Disease Lötscher, Fabian Seitz, Luca Simeunovic, Helena Sarbu, Adela-Cristina Porret, Naomi A. Feldmeyer, Laurence Borradori, Luca Bonadies, Nicolas Maurer, Britta Front Immunol Immunology 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. Frontiers Media S.A. 2022-01-20 /pmc/articles/PMC8811255/ /pubmed/35126364 http://dx.doi.org/10.3389/fimmu.2021.800149 Text en Copyright © 2022 Lötscher, Seitz, Simeunovic, Sarbu, Porret, Feldmeyer, Borradori, Bonadies and Maurer https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Immunology Lötscher, Fabian Seitz, Luca Simeunovic, Helena Sarbu, Adela-Cristina Porret, Naomi A. Feldmeyer, Laurence Borradori, Luca Bonadies, Nicolas Maurer, Britta Case Report: Genetic Double Strike: VEXAS and TET2-Positive Myelodysplastic Syndrome in a Patient With Long-Standing Refractory Autoinflammatory Disease |
title | Case Report: Genetic Double Strike: VEXAS and TET2-Positive Myelodysplastic Syndrome in a Patient With Long-Standing Refractory Autoinflammatory Disease |
title_full | Case Report: Genetic Double Strike: VEXAS and TET2-Positive Myelodysplastic Syndrome in a Patient With Long-Standing Refractory Autoinflammatory Disease |
title_fullStr | Case Report: Genetic Double Strike: VEXAS and TET2-Positive Myelodysplastic Syndrome in a Patient With Long-Standing Refractory Autoinflammatory Disease |
title_full_unstemmed | Case Report: Genetic Double Strike: VEXAS and TET2-Positive Myelodysplastic Syndrome in a Patient With Long-Standing Refractory Autoinflammatory Disease |
title_short | Case Report: Genetic Double Strike: VEXAS and TET2-Positive Myelodysplastic Syndrome in a Patient With Long-Standing Refractory Autoinflammatory Disease |
title_sort | case report: genetic double strike: vexas and tet2-positive myelodysplastic syndrome in a patient with long-standing refractory autoinflammatory disease |
topic | Immunology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8811255/ https://www.ncbi.nlm.nih.gov/pubmed/35126364 http://dx.doi.org/10.3389/fimmu.2021.800149 |
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