Methodology and clinical utility of longitudinal UBA1 tracking in VEXAS syndrome

Carmelo Gurnari^{1

2}, Elisa Galossi¹, Eleonora Lumia¹, Alfonso Piciocchi³, Mariadomenica Divona¹, Elisa Casciani¹, Francesca Romano¹, Elisa Diral⁴, Alessandro Tomelleri⁵, Federico Caroni⁶, Antonio Vitale⁷, Gregorio Maria Bergonzi⁴, Annalisa Condorelli⁸, Giorgia Battipaglia⁹, Erika Morsia¹⁰, Elena Crisà¹¹, Paola Triggianese¹, Arianna Savi¹², Chiara Cardamone¹³, Matteo Dragani¹⁴, Giulia Rivoli¹⁴, Federica Pilo¹⁵, Davide Firinu¹⁶, Sara Plebani¹⁷, Francesco D'Agostino¹⁸, Alessandro D'Ambrosio¹⁹, Katja Sockel²⁰, Cristina Papayannidis²¹, Silvia Salmoiraghi⁸, Fabrizio Pane⁹, Monica Bocchia⁶, Luca Cantarini⁷, Marco Frigeni⁸, Corrado Campochiaro⁵, Lorenzo Dagna⁵, Raffaella Greco⁴, Fabio Ciceri⁴, Orietta Spinelli⁸, Christian Thiede²⁰, Maria Teresa Voso¹

Affiliations

¹ Department of Biomedicine and Prevention, University of Rome Tor Vergata, Rome, Italy.
² Translational Hematology and Oncology Research Department, Taussig Cancer Center, Cleveland Clinic, Cleveland, Ohio, USA.
³ GIMEMA Foundation, Rome, Italy.
⁴ Unit of Hematology and Bone Marrow Transplantation, IRCCS San Raffaele Hospital, Vita-Salute San Raffaele University, Milan, Italy.
⁵ Unit of Immunology, Rheumatology, Allergy and Rare Diseases (UnIRAR), IRCCS Ospedale San Raffaele & Vita-Salute San Raffaele University, Milan, Italy.
⁶ Hematology Unit, Azienda Ospedaliero-Universitaria Senese, University of Siena, Siena, Italy.
⁷ Department of Medical Sciences, Surgery and Neurosciences, Rheumatology Unit, University of Siena and Azienda Ospedaliero-Universitaria Senese [European Reference Network (ERN) for Rare Immunodeficiency, Autoinflammatory and Autoimmune Diseases (RITA) Center], Siena, Italy.
⁸ Department of Oncology and Hematology, ASST Papa Giovanni XXIII, SC Ematologia, Bergamo, Italy.
⁹ Department of Clinical Medicine and Surgery, University Federico II, Naples, Italy.
¹⁰ Hematology Department, University of Ancona, Azienda Ospedaliera Universitaria Ospedali Riuniti di Ancona, Ancona, Italy.
¹¹ Candiolo Cancer Institute, FPO-IRCCS, Candiolo (Torino), Italy.
¹² Department of Clinical and Biological Sciences, University of Turin, Torino, Italy.
¹³ Division of Allergy and Clinical Immunology, University of Salerno, Salerno, Italy.
¹⁴ Hematology and Cellular Therapy Unit, IRCCS Ospedale Policlinico San Martino, Genoa, Italy.
¹⁵ Hematology and BMT Unit, 'A.Businco' Hospital, AOB, Cagliari, Italy.
¹⁶ Department of Medical Sciences and Public Health, University of Cagliari, Cagliari, Italy.
¹⁷ Hematology, San Salvatore Hospital, L'Aquila, Italy.
¹⁸ UOC Hematology, IRCCS Ospedale Casa Sollievo Della Sofferenza, San Giovanni Rotondo, Italy.
¹⁹ AORN S.Anna e S. Sebastiano, Caserta, Italy.
²⁰ Department of Internal Medicine I, University Hospital Dresden, Technical University Dresden, Dresden, Germany.
²¹ IRCCS Azienda Ospedaliero-Universitaria di Bologna, Istituto di Ematologia 'Seràgnoli', Bologna, Italy.

PMID: 39533868
DOI: 10.1111/bjh.19897

Methodology and clinical utility of longitudinal UBA1 tracking in VEXAS syndrome

Carmelo Gurnari et al. Br J Haematol. 2025 Jan.

. 2025 Jan;206(1):331-336.

doi: 10.1111/bjh.19897. Epub 2024 Nov 13.

Authors

Affiliations

¹ Department of Biomedicine and Prevention, University of Rome Tor Vergata, Rome, Italy.
² Translational Hematology and Oncology Research Department, Taussig Cancer Center, Cleveland Clinic, Cleveland, Ohio, USA.
³ GIMEMA Foundation, Rome, Italy.
⁴ Unit of Hematology and Bone Marrow Transplantation, IRCCS San Raffaele Hospital, Vita-Salute San Raffaele University, Milan, Italy.
⁵ Unit of Immunology, Rheumatology, Allergy and Rare Diseases (UnIRAR), IRCCS Ospedale San Raffaele & Vita-Salute San Raffaele University, Milan, Italy.
⁶ Hematology Unit, Azienda Ospedaliero-Universitaria Senese, University of Siena, Siena, Italy.
⁷ Department of Medical Sciences, Surgery and Neurosciences, Rheumatology Unit, University of Siena and Azienda Ospedaliero-Universitaria Senese [European Reference Network (ERN) for Rare Immunodeficiency, Autoinflammatory and Autoimmune Diseases (RITA) Center], Siena, Italy.
⁸ Department of Oncology and Hematology, ASST Papa Giovanni XXIII, SC Ematologia, Bergamo, Italy.
⁹ Department of Clinical Medicine and Surgery, University Federico II, Naples, Italy.
¹⁰ Hematology Department, University of Ancona, Azienda Ospedaliera Universitaria Ospedali Riuniti di Ancona, Ancona, Italy.
¹¹ Candiolo Cancer Institute, FPO-IRCCS, Candiolo (Torino), Italy.
¹² Department of Clinical and Biological Sciences, University of Turin, Torino, Italy.
¹³ Division of Allergy and Clinical Immunology, University of Salerno, Salerno, Italy.
¹⁴ Hematology and Cellular Therapy Unit, IRCCS Ospedale Policlinico San Martino, Genoa, Italy.
¹⁵ Hematology and BMT Unit, 'A.Businco' Hospital, AOB, Cagliari, Italy.
¹⁶ Department of Medical Sciences and Public Health, University of Cagliari, Cagliari, Italy.
¹⁷ Hematology, San Salvatore Hospital, L'Aquila, Italy.
¹⁸ UOC Hematology, IRCCS Ospedale Casa Sollievo Della Sofferenza, San Giovanni Rotondo, Italy.
¹⁹ AORN S.Anna e S. Sebastiano, Caserta, Italy.
²⁰ Department of Internal Medicine I, University Hospital Dresden, Technical University Dresden, Dresden, Germany.
²¹ IRCCS Azienda Ospedaliero-Universitaria di Bologna, Istituto di Ematologia 'Seràgnoli', Bologna, Italy.

PMID: 39533868
DOI: 10.1111/bjh.19897

Abstract

Vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic (VEXAS) is a haemato-inflammatory syndrome genetically defined by somatic mutations in the X-linked UBA1 gene, typically Val/Thr/Leu substitutions at the Met41 hotspot. Clinical manifestations are heterogeneous and refractory to most haemato-rheumatological treatments. To date, no guidelines exist for the management of VEXAS, and scarce is the evidence on methodology and clinical significance of longitudinal UBA1 clonal burden evaluation upon therapy. Here, we validated a method to quantify UBA1 clonal burden and explored its applicability in patients with VEXAS. Given the different treatment interactions, droplet digital polymerase chain reaction (ddPCR) may allow for informed therapeutic decisions and implementation of personalized strategies.

Keywords: autoimmune disease; molecular diagnostics; mutation detection; myeloid neoplasia.

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References

REFERENCES

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Methodology and clinical utility of longitudinal UBA1 tracking in VEXAS syndrome

Affiliations

Methodology and clinical utility of longitudinal UBA1 tracking in VEXAS syndrome

Authors

Affiliations

Abstract

References

REFERENCES

MeSH terms

Substances

Supplementary concepts

Grants and funding

LinkOut - more resources

Full Text Sources

Research Materials

Miscellaneous