Diversity of XMEN Disease: Description of 2 Novel Variants and Analysis of the Lymphocyte Phenotype
| Autor: | Bethany Pillay, Elizabeth Klinken, Jonathan Chan, Lisa Worley, Ben A Wood, Andrew McLean-Tooke, Gulbu Uzel, Stuart G. Tangye, Bruce Bennetts, Kathryn Payne, Cindy S. Ma, Paul Gray, Emily S.J. Edwards, Dorothy Hung, Glenn M. Marshall, Richard Mitchell |
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| Rok vydání: | 2019 |
| Předmět: |
Adult
Male Epstein-Barr Virus Infections Herpesvirus 4 Human T cell Lymphocyte Immunology XMEN disease X-Linked Combined Immunodeficiency Diseases Chimerism Immunophenotyping Immune system Lymphopenia Neoplasms medicine Humans Immunology and Allergy Magnesium Child Cation Transport Proteins Immunodeficiency business.industry Hematopoietic Stem Cell Transplantation CD28 Cell Differentiation NKG2D medicine.disease medicine.anatomical_structure NK Cell Lectin-Like Receptor Subfamily K Leukocytes Mononuclear business Immunologic Memory |
| Zdroj: | Journal of Clinical Immunology. 40:299-309 |
| ISSN: | 1573-2592 0271-9142 |
| Popis: | Variants in MAGT1 have been identified as the cause of an immune deficiency termed X-linked immunodeficiency with magnesium defect, Epstein-Barr virus (EBV) infection and neoplasia (XMEN) disease. Here, we describe 2 cases of XMEN disease due to novel mutations in MAGT1, one of whom presented with classical features of XMEN disease and another who presented with a novel phenotype including probable CNS vasculitis, HHV-8 negative multicentric Castelman disease and severe molluscum contagiosum, thus highlighting the clinical diversity that may be seen in this condition. Peripheral blood immunophenotyping of these 2 patients, together with an additional 4 XMEN patients, revealed reduced NKG2D expression, impaired CD28 expression on CD8+ T cells, CD4+ T cell lymphopenia, an inverted CD4:CD8 ratio and decreased memory B cells. In addition, we showed for the first time alterations to the CD8+ T cell memory compartment, reduced CD56hi NK cells, MAIT and iNKT cells, as well as compromised differentiation of naive CD4+ T cells into IL-21-producing Tfh-type cells in vitro. Both patients were treated with supplemental magnesium with limited benefit. However, one patient has undergone allogeneic haematopoietic stem cell transplant, with full donor chimerism and immune reconstitution. These results expand our understanding of the clinical and immunological phenotype in XMEN disease, adding to the current literature, which we further discuss here. |
| Databáze: | OpenAIRE |
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