Cargando…

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...

Descripción completa

Detalles Bibliográficos
Autores principales: Lötscher, Fabian, Seitz, Luca, Simeunovic, Helena, Sarbu, Adela-Cristina, Porret, Naomi A., Feldmeyer, Laurence, Borradori, Luca, Bonadies, Nicolas, Maurer, Britta
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
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
_version_ 1784644390537396224
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
work_keys_str_mv AT lotscherfabian casereportgeneticdoublestrikevexasandtet2positivemyelodysplasticsyndromeinapatientwithlongstandingrefractoryautoinflammatorydisease
AT seitzluca casereportgeneticdoublestrikevexasandtet2positivemyelodysplasticsyndromeinapatientwithlongstandingrefractoryautoinflammatorydisease
AT simeunovichelena casereportgeneticdoublestrikevexasandtet2positivemyelodysplasticsyndromeinapatientwithlongstandingrefractoryautoinflammatorydisease
AT sarbuadelacristina casereportgeneticdoublestrikevexasandtet2positivemyelodysplasticsyndromeinapatientwithlongstandingrefractoryautoinflammatorydisease
AT porretnaomia casereportgeneticdoublestrikevexasandtet2positivemyelodysplasticsyndromeinapatientwithlongstandingrefractoryautoinflammatorydisease
AT feldmeyerlaurence casereportgeneticdoublestrikevexasandtet2positivemyelodysplasticsyndromeinapatientwithlongstandingrefractoryautoinflammatorydisease
AT borradoriluca casereportgeneticdoublestrikevexasandtet2positivemyelodysplasticsyndromeinapatientwithlongstandingrefractoryautoinflammatorydisease
AT bonadiesnicolas casereportgeneticdoublestrikevexasandtet2positivemyelodysplasticsyndromeinapatientwithlongstandingrefractoryautoinflammatorydisease
AT maurerbritta casereportgeneticdoublestrikevexasandtet2positivemyelodysplasticsyndromeinapatientwithlongstandingrefractoryautoinflammatorydisease