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Case Reports
. 2023 Nov 29:10:1264329.
doi: 10.3389/fmed.2023.1264329. eCollection 2023.

Case report: XMEN disease: a patient with recurrent Hodgkin lymphoma and immune thrombocytopenia

Pieter F de Groot  1 , Arjan J Kwakernaak  1   2 , Ester M M van Leeuwen  2 , Rosalina M L van Spaendonk  3 , Evert-Jan Kooi  4 , Daphne de Jong  4 , Taco W Kuijpers  2   5 , Josée M Zijlstra  6 , Godelieve J de Bree  2   7
Affiliations
Case Reports

Case report: XMEN disease: a patient with recurrent Hodgkin lymphoma and immune thrombocytopenia

Pieter F de Groot et al. Front Med (Lausanne). .

Abstract

Here we present the case of a 28-year-old man with X-linked immunodeficiency with magnesium defect, Epstein-Barr virus (EBV) infection and neoplasia (XMEN) disease. He presented with immune thrombocytopenia within 1 year after successful autologous hematopoietic stem cell transplantation for recurrent EBV-associated classical Hodgkin lymphoma (CHL). The combination of EBV- associated malignancy, autoimmunity, recurrent airway infections at young age and bronchiectasis, prompted immunological investigation for an inborn error of immunity (IEI). Genetic testing revealed XMEN disease. XMEN disease is characterized by a glycosylation defect due to mutations in the MAGT1 gene. Germline mutations in the MAGT1 gene disrupt glycosylation of the NKG2D receptor in immune cells, including natural killer and CD8-positive T cells, vital for immune surveillance, especially against EBV. Consequently, individuals with XMEN disease, are prone to EBV-associated lymphoproliferative disorders in addition to auto-immunity. Early recognition of adult onset IEI-related B-lymphoproliferative disorders, including CHL is of vital importance for treatment decisions, including (allogeneic) haematopoietic stem cell transplantation and family screening.

Keywords: Classical Hodgkin lymphoma (CHL); XMEN disease; hematopoietic stem cell transplantation; immune thrombocytopenia (ITP); inborn error of immunity.

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Conflict of interest statement

GB had a grant from Takeda paid through her institution. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

FIGURE 1
FIGURE 1
(A–D) Histopathology of the supraclavicular lymph node at initial presentation in 2015 (panel A–D) and right cervical lymph node at relapse in 2019 (panel E–H). (A) Hematoxylin-eosin stain shows scattered large Hodgkin Reed-Sternberg (HRS) cells in a reactive background of small lymphocytes, histiocytes and sporadic eosinophilic granulocytes; (B) EBER (Epstein–Barr encoding region) shows sparse positive small and slightly enlarged lymphocytes, but HRS-cells are negative; (C) CD30 is uniformly positive in HRS-cells as well as in a range of immunoblasts and small lymphocytes; (D) CD20 is negative in HRS-cells. (E) Hematoxylin-eosin stain shows a larger morphological spectrum of scattered large HRS cells and immunoblasts; (F) EBER shows a high proportion of positive cells with a typical range of HRS-cells to small lymphocytes; (G): CD30 is uniformly positive in HRS-cells as well as in a range of immunoblasts and small lymphocytes; (H) CD79a positive in these cells.
FIGURE 2
FIGURE 2
Flowcytometric analysis of cell surface NKG2D expression on PBMC, gated on CD3+CD4+ T cells, CD3+CD8+ T cells, CD3-CD16/56+ NK cells, of a healthy control and the patient. Histograms normalized for cell number per subset. MFI: mean fluorescence intensity for NKG2D cell surface expression on NK-cells (yellow), CD8-positive T-cells (blue) and CD4-positive T-cells (red).
See this image and copyright information in PMC

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