VEXAS (vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic) syndrome is an autoinflammatory disorder characterized by somatic mutations in the UBA1 gene in hematopoietic stem cells and associated with diffuse inflammation and myelodysplastic changes amongst others. Due to unspecific symptoms the diagnosis is challenging, and there is an unmet need for clinical markers to select patients for genetic examination. Sera of 9 patients with confirmed VEXAS syndrome were analyzed for immunoglobulin (Ig)G4 levels. Disease parameters and clinical response to therapy were correlated with IgG4 levels. A histopathological examination was performed on the available samples to exclude IgG4-related autoimmune diseases. In this cohort, 44% of our patients showed markedly elevated serum IgG4 levels. We observed a general trend toward a positive correlation between IgG4 levels and inflammatory markers as well as a correlation with clinical response in one patient. Histopathological analysis showed no evidence of IgG4 related disease. IgG4 levels seem to be elevated in a relevant fraction of patients with VEXAS syndrome. In some cases, this might be misinterpreted as IgG4-related disease, a pitfall clinicians should be aware of. Furthermore, our results warrant the further evaluation of a potential correlation of IgG4 levels with disease activity and severity of inflammation. IgG4 serum levels might be useful in the evaluation of the disease course.
