Frontiers in Immunology (Apr 2021)
Case Report: VEXAS Syndrome: From Mild Symptoms to Life-Threatening Macrophage Activation Syndrome
- Frederik Staels,
- Frederik Staels,
- Albrecht Betrains,
- Albrecht Betrains,
- F. J. Sherida H. Woei-A-Jin,
- F. J. Sherida H. Woei-A-Jin,
- Nancy Boeckx,
- Nancy Boeckx,
- Marielle Beckers,
- Marielle Beckers,
- An Bervoets,
- An Bervoets,
- Mathijs Willemsen,
- Mathijs Willemsen,
- Barbara Neerinckx,
- Barbara Neerinckx,
- Stephanie Humblet-Baron,
- Daniel Engelbert Blockmans,
- Daniel Engelbert Blockmans,
- Steven Vanderschueren,
- Steven Vanderschueren,
- Rik Schrijvers,
- Rik Schrijvers,
- Rik Schrijvers
Affiliations
- Frederik Staels
- Laboratory of Adaptive Immunology, Immunology and Transplantation, Department of Microbiology, KU Leuven, Leuven, Belgium
- Frederik Staels
- Allergy and Clinical Immunology Research Group, Immunology and Transplantation, Department of Microbiology, KU Leuven, Leuven, Belgium
- Albrecht Betrains
- Department of General Internal Medicine, University Hospitals Leuven, Leuven, Belgium
- Albrecht Betrains
- Laboratory of Clinical Infectious and Inflammatory Disease, Immunology and Transplantation, Department of Microbiology, KU Leuven, Leuven, Belgium
- F. J. Sherida H. Woei-A-Jin
- Department of General Medical Oncology, Leuven Cancer Institute, University Hospitals Leuven, Leuven, Belgium
- F. J. Sherida H. Woei-A-Jin
- Laboratory of Experimental Oncology, Department of Oncology, KU Leuven, Leuven, Belgium
- Nancy Boeckx
- Clinical Department of Laboratory Medicine, University Hospitals Leuven, Leuven, Belgium
- Nancy Boeckx
- Laboratory of Experimental Hematology, Department of Oncology, KU Leuven, Leuven, Belgium
- Marielle Beckers
- Laboratory of Experimental Hematology, Department of Oncology, KU Leuven, Leuven, Belgium
- Marielle Beckers
- Department of Hematology, University Hospitals Leuven, Leuven, Belgium
- An Bervoets
- 0Department of Dermatology, University Hospitals Leuven, Leuven, Belgium
- An Bervoets
- 1Department of Dermatology, University Hospitals Antwerpen, Edegem, Belgium
- Mathijs Willemsen
- Laboratory of Adaptive Immunology, Immunology and Transplantation, Department of Microbiology, KU Leuven, Leuven, Belgium
- Mathijs Willemsen
- 2VIB-KU Leuven Center for Brain and Disease Research, KU Leuven, Leuven, Belgium
- Barbara Neerinckx
- 3Department of Rheumatology, University Hospitals Leuven, Leuven, Belgium
- Barbara Neerinckx
- 4Skeletal Biology and Engineering Research Center, Department of Development and Regeneration, KU Leuven, Leuven, Belgium
- Stephanie Humblet-Baron
- Laboratory of Adaptive Immunology, Immunology and Transplantation, Department of Microbiology, KU Leuven, Leuven, Belgium
- Daniel Engelbert Blockmans
- Department of General Internal Medicine, University Hospitals Leuven, Leuven, Belgium
- Daniel Engelbert Blockmans
- Laboratory of Clinical Infectious and Inflammatory Disease, Immunology and Transplantation, Department of Microbiology, KU Leuven, Leuven, Belgium
- Steven Vanderschueren
- Department of General Internal Medicine, University Hospitals Leuven, Leuven, Belgium
- Steven Vanderschueren
- Laboratory of Clinical Infectious and Inflammatory Disease, Immunology and Transplantation, Department of Microbiology, KU Leuven, Leuven, Belgium
- Rik Schrijvers
- Laboratory of Adaptive Immunology, Immunology and Transplantation, Department of Microbiology, KU Leuven, Leuven, Belgium
- Rik Schrijvers
- Allergy and Clinical Immunology Research Group, Immunology and Transplantation, Department of Microbiology, KU Leuven, Leuven, Belgium
- Rik Schrijvers
- Department of General Internal Medicine, University Hospitals Leuven, Leuven, Belgium
- DOI
- https://doi.org/10.3389/fimmu.2021.678927
- Journal volume & issue
-
Vol. 12
Abstract
Recently, a novel disorder coined VEXAS (vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic) syndrome was identified in patients with adult-onset inflammatory syndromes, often accompanied by myelodysplastic syndrome1. All patients had myeloid lineage-restricted somatic mutations in UBA1 affecting the Met41 residue of the protein and resulting in decreased cellular ubiquitylation activity and hyperinflammation. We here describe the clinical disease course of two VEXAS syndrome patients with somatic UBA1 mutations of which one with a mild phenotype characterized by recurrent rash and symmetric polyarthritis, and another who was initially diagnosed with idiopathic multicentric Castleman disease and developed macrophage activation syndrome as a complication of the VEXAS syndrome. The latter patients was treated with anti-IL6 therapy (siltuximab) leading to a resolution of systemic symptoms and reduction of transfusion requirements.
Keywords