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| Home > Articles > Published articles > Spanish cohort of VEXAS syndrome : |
(Hospital Clínic i Provincial de Barcelona) (Hospital Clínic i Provincial de Barcelona) (Hospital Álvaro Cunqueiro) (Instituto de Investigación Sanitaria del Principado de Asturias) (Hospital Clínic i Provincial de Barcelona) (Hospital Clínic i Provincial de Barcelona) (Hospital Clínic i Provincial de Barcelona) (Universidad Autónoma de Madrid) (Universidad Miguel Hernández de Elche) (Hospital Valle del Nalón) (Fundació Althaia de Manresa) (Parc Taulí Hospital Universitari. Institut d'Investigació i Innovació Parc Taulí (I3PT)) (Hospital Universitari General de Catalunya) (Hospital Universitari de Vinalopo) (Hospital Clínic i Provincial de Barcelona) (Hospital Clínic i Provincial de Barcelona) (Hospital Clínic i Provincial de Barcelona) (Hospital Clínic i Provincial de Barcelona) (Hospital Clínic i Provincial de Barcelona) (Hospital Clínic i Provincial de Barcelona) (Institut Hospital del Mar d'Investigacions Mèdiques) (Institut Hospital del Mar d'Investigacions Mèdiques) (Institut Hospital del Mar d'Investigacions Mèdiques) (Universitat Pompeu Fabra) (Universitat de Barcelona) (Hospital Clínic i Provincial de Barcelona) (Hospital Clínic i Provincial de Barcelonaa)| Date: | 2023 |
| Abstract: | The vacuoles, E1-enzyme, X linked, autoinflammatory and somatic (VEXAS) syndrome is an adult-onset autoinflammatory disease (AID) due to postzygotic UBA1 variants. To investigate the presence of VEXAS syndrome among patients with adult-onset undiagnosed AID. Additional studies evaluated the mosaicism distribution and the circulating cytokines. Gene analyses were performed by both Sanger and amplicon-based deep sequencing. Patients' data were collected from their medical charts. Cytokines were quantified by Luminex. Genetic analyses of enrolled patients (n=42) identified 30 patients carrying UBA1 pathogenic variants, with frequencies compatible for postzygotic variants. All patients were male individuals who presented with a late-onset disease (mean 67. 5 years; median 67. 0 years) characterised by cutaneous lesions (90%), fever (66. 7%), pulmonary manifestations (66. 7%) and arthritis (53. 3%). Macrocytic anaemia and increased erythrocyte sedimentation rate and ferritin were the most relevant analytical abnormalities. Glucocorticoids ameliorated the inflammatory manifestations, but most patients became glucocorticoid-dependent. Positive responses were obtained when targeting the haematopoietic component of the disease with either decitabine or allogeneic haematopoietic stem cell transplantation. Additional analyses detected the UBA1 variants in both haematopoietic and non-haematopoietic tissues. Finally, analysis of circulating cytokines did not identify inflammatory mediators of the disease. Thirty patients with adult-onset AID were definitively diagnosed with VEXAS syndrome through genetic analyses. Despite minor interindividual differences, their main characteristics were in concordance with previous reports. We detected for the first time the UBA1 mosaicism in non-haematopoietic tissue, which questions the previous concept of myeloid-restricted mosaicism and may have conceptual consequences for the disease mechanisms. |
| Grants: | Agencia Estatal de Investigación RTI2018-096824-B-C21 Agencia Estatal de Investigación RTI2018-096824-B-C22 Agencia Estatal de Investigación PID2021-125106OB-C31 Agencia Estatal de Investigación PID2021-125106OB-C32 Instituto de Salud Carlos III PI19/01567 |
| Rights: | Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, sempre que no sigui amb finalitats comercials, i sempre que es reconegui l'autoria de l'obra original.  |
| Language: | Anglès |
| Document: | Article ; recerca ; Versió publicada |
| Subject: | Immune system diseases ; Inflammation ; Polymorphism, genetic |
| Published in: | Annals of the rheumatic diseases, Vol. 82 (september 2023) , p. 1594-1605, ISSN 1468-2060 |
