Samuel D. Chauvin, United States of America
National Institute of Allergy and Infectious Diseases Molecular Development of the Immune System SectionPresenter of 1 Presentation
MALIGNANCY IN XMEN DISEASE
Abstract
Background and Aims
X-linked immunodeficiency with magnesium defect, Epstein-Barr virus (EBV) infection, and neoplasia (XMEN) disease is caused by loss of function (LOF) mutations in the magnesium transporter 1 gene (MAGT1). Patients have an inverted CD4:CD8 ratio with CD4 lymphocytopenia, increased B cells, and invariably, decreased expression of the activator receptor “Natural-Killer Group 2, member D” (NKG2D) on natural killer (NK) and CD8+ T cells. NKG2D loss results in impaired cytotoxicity and increased susceptibility to malignancies.
Methods
We reviewed the medical records and pathology slides of 9 patients with genetic confirmation of XMEN disease and histopathological diagnosis of malignancy. Patients with XMEN disease and no history of malignancy were excluded for this analysis. All subjects had variants in the MAGT1 gene that resulted in loss of protein expression. Decreased NKG2D surface expression was confirmed by flow cytometry. All subjects provided written informed consent in accordance with the Declaration of Helsinki.
Results
The most common neoplasia associated with XMEN disease was classical Hodgkin lymphoma (n=4). Burkitt’s lymphoma, diffuse large B cell lymphoma, EBV-positive lymphoproliferative disease, and liposarcoma were less frequently observed. Age of cancer onset varied from 7 to 45 years.
Conclusions
XMEN disease is a combined primary immunodeficiency that results in chronic EBV infection and increased risk for malignancy. EBV-encoded RNA (EBER)-positive Hodgkin lymphoma is the most common form of malignancy observed in our cohort of XMEN patients.