Spanish cohort of VEXAS syndrome: clinical manifestations, outcome of treatments and novel evidences about UBA1 mosaicism

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• dc.contributor.author Mascaró, Jose Manuel
• dc.contributor.author Tejedor Vaquero, Sonia, 1988-
• dc.contributor.author Magri, Giuliana, 1978-
• dc.contributor.author Cerutti, Andrea, 1965-
• dc.contributor.author Aróstegui Gorospe, Juan Ignacio
• dc.date.accessioned 2024-04-25T06:01:33Z
• dc.date.available 2024-04-25T06:01:33Z
• dc.date.issued 2023
• dc.description.abstract Background: The vacuoles, E1-enzyme, X linked, autoinflammatory and somatic (VEXAS) syndrome is an adult-onset autoinflammatory disease (AID) due to postzygotic UBA1 variants. Objectives: To investigate the presence of VEXAS syndrome among patients with adult-onset undiagnosed AID. Additional studies evaluated the mosaicism distribution and the circulating cytokines. Methods: 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. Results: 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. Conclusion: 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.
• dc.format.mimetype application/pdf
• dc.identifier.citation Mascaro JM, Rodriguez-Pinto I, Poza G, Mensa-Vilaro A, Fernandez-Martin J, Caminal-Montero L, et al. Spanish cohort of VEXAS syndrome: clinical manifestations, outcome of treatments and novel evidences about UBA1 mosaicism. Ann Rheum Dis. 2023 Dec;82(12):1594-605. DOI: 10.1136/ard-2023-224460
• dc.identifier.doi http://dx.doi.org/10.1136/ard-2023-224460
• dc.identifier.issn 0003-4967
• dc.identifier.uri http://hdl.handle.net/10230/59903
• dc.language.iso eng
• dc.publisher BMJ Publishing Group
• dc.relation.ispartof Ann Rheum Dis. 2023 Dec;82(12):1594-605
• dc.rights © Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ. This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated, and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/.
• dc.rights.accessRights info:eu-repo/semantics/openAccess
• dc.rights.uri http://creativecommons.org/licenses/by-nc/4.0/
• dc.subject.keyword Immune system diseases
• dc.subject.keyword Inflammation
• dc.subject.keyword Polymorphism
• dc.subject.keyword Genetic
• dc.title Spanish cohort of VEXAS syndrome: clinical manifestations, outcome of treatments and novel evidences about UBA1 mosaicism
• dc.type info:eu-repo/semantics/article
• dc.type.version info:eu-repo/semantics/publishedVersion