Spanish cohort of VEXAS syndrome: clinical manifestations, outcome of treatments and novel evidences about UBA1 mosaicism.
Обработка статьи · этапы, ошибки и управление
Ошибки и ограничения
История · было → стало
Состояние обновляется каждые 5 секунд, пока блок открыт. Процент показывается только там, где известен объём работы. Пауза останавливает продолжение этапа; текущий запрос к источнику может завершиться.
Mascaro Jose Manuel, Rodriguez-Pinto Ignasi, Poza Gabriela, Mensa-Vilaro Anna, Fernandez-Martin Julian, Caminal-Montero Luis, Espinosa Gerard, Hernández-Rodríguez Jose, Diaz Marina, Rita-Marques Joana, Sanmarti Raimon, Castañeda Santos, Colunga Dolores, Coto-Hernández Rubén, Fanlo Patricia, Elejalde Jose Ignacio, Bujan Segundo, Figueras Ignasi, Marco Francisco Manuel, Andrés Mariano, Suárez Silvia, Gonzalez-Garcia Andres, Fustà-Novell Xavier, Garcia-Belando Clara, Granados Ana, Fernandez-Figueras Maria Teresa, Quilis Neus, Orriols-Caba Maria, Gómez de la Torre Ricardo, Cid Maria Cinta, Espígol-Frigolé Georgina, Alvarez-Abella Alba, Labrador Eztizen, Rozman Maria, Lopez-Guerra Monica, Castillo Paola, Alamo-Moreno Jose R, Gonzalez-Roca Eva, Plaza Susana, Fabregat Virginia, Lara Rocio, Vicente-Rabaneda Esther F, Tejedor-Vaquero Sonia, Magri Giuliana, Bonet Nuria, Solis-Moruno Manuel, Cerutti Andrea, Fornas Oscar, Casals Ferran, Yagüe Jordi, Aróstegui Juan I
Аннотация
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.