Successful treatment of acute Epstein–Barr virus infection associated with X‐linked lymphoproliferative disorder with rituximab

Bond, Jonathan; Shahdadpuri, Raveen; Mahon, Corrina Mc; O'Marcaigh, Aengus; Cotter, Maura B.; Smith, Owen

doi:10.1002/pbc.21081

Cited by 10 publications

(8 citation statements)

References 3 publications

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“…10,11 Importantly, the control of EBV-infected B cells seems to be a key determinant in driving fulminant IM in XLP patients given that B cell-depletion therapy with rituximab resolves symptoms and reduces viral DNA among circulating lymphocytes. 12,13 Together, these findings support the hypothesis that SAP-dependent immunity is essential for the surveillance of infected and malignant B cells.…”

Section: Introductionsupporting

confidence: 74%

2B4-SAP signaling is required for the priming of naive CD8⁺ T cells by antigen-expressing B cells and B lymphoma cells

et al. 2016

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Mutations in SH2D1A gene that encodes SAP (SLAM-associated protein) result in X-linked lymphoproliferative disease (XLP), a rare primary immunodeficiency disease defined by exquisite sensitivity to the B-lymphotropic Epstein-Barr virus (EBV) and B cell lymphomas. However, the precise mechanism of how the loss of SAP function contributes to extreme vulnerability to EBV and the development of B cell lymphomas remains unclear. Here, we investigate the hypothesis that SAP is critical for CD8C T cell immune surveillance of antigen (Ag)-expressing B cells or B lymphoma cells under conditions of defined T cell receptor (TCR) signaling. Sh2d1a¡/¡ CD8 C T cells exhibited greatly diminished proliferation relative to wild type when Ag-presenting-B cells or -B lymphoma cells served as the primary Ag-presenting cell (APC). By contrast, Sh2d1a¡/¡ CD8 C T cells responded equivalently to wild-type CD8 C T cells when B cell-depleted splenocytes, melanoma cells or breast carcinoma cells performed Ag presentation. Through application of signaling lymphocyte activation molecule (SLAM) family receptor blocking antibodies or SLAM family receptor-deficient CD8 C T cells and APCs, we found that CD48 engagement on the B cell surface by 2B4 is crucial for initiating SAP-dependent signaling required for the Ag-driven CD8 C T cell proliferation and differentiation. Altogether, a pivotal role for SAP in promoting the expansion and differentiation of B cell-primed viral-specific naive CD8C T cells may explain the selective immune deficiency of XLP patients to EBV and B cell lymphomas.

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Section: Introductionsupporting

confidence: 74%

2B4-SAP signaling is required for the priming of naive CD8⁺ T cells by antigen-expressing B cells and B lymphoma cells

et al. 2016

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“…Some patients have been successfully treated with rituximab before chemotherapy and HSCT. 466,467 Syndromes with autoimmunity. Autoimmune lymphoproliferative syndrome and autoimmune lymphoproliferative syndrome-related disorders.…”

Section: Diseases Of Immune Dysregulationmentioning

confidence: 99%

Practice parameter for the diagnosis and management of primary immunodeficiency

Bernstein¹,

Blessing-Moore²,

Khan³

et al. 2015

Journal of Allergy and Clinical Immunology

587

494

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The American Academy of Allergy, Asthma & Immunology (AAAAI) and the American College of Allergy, Asthma & Immunology (ACAAI) have jointly accepted responsibility for establishing the "Practice parameter for the diagnosis and management of primary immunodeficiency." This is a complete and comprehensive document at the current time. The medical environment is a changing environment, and not all recommendations will be appropriate for all patients. Because this document incorporated the efforts of many participants, no single individual, including those who served on the Joint Task Force, is authorized to provide an official AAAAI or ACAAI interpretation of these practice parameters. Any request for information about or an interpretation of these practice parameters by the AAAAI or ACAAI should be directed to the Executive Offices of the AAAAI, the ACAAI, and the Joint Council of Allergy, Asthma & Immunology. These parameters are not designed for use by pharmaceutical companies in drug promotion.

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“…Two XLP patients who presented with acute EBV infection were successfully treated with rituximab and were free from EBV-HLH and lymphoma for a prolonged period. In addition, rituximab combined with methylprednisolone and intravenous immunoglobulin were administered to an XLP-1 patient with EBV-HLH, and the patient achieved a remission [20]. Patient 1 was also associated with EBV-associated encephalitis and lymphoproliferative disorder.…”

Section: Discussionmentioning

confidence: 99%

Characterization of Epstein-Barr virus (EBV)-infected cells in EBV-associated hemophagocytic lymphohistiocytosis in two patients with X-linked lymphoproliferative syndrome type 1 and type 2

et al. 2012

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BackgroundX-linked lymphoproliferative syndrome (XLP) is a rare inherited immunodeficiency by an extreme vulnerability to Epstein-Barr virus (EBV) infection, frequently resulting in hemophagocytic lymphohistiocytosis (HLH). XLP are now divided into type 1 (XLP-1) and type 2 (XLP-2), which are caused by mutations of SH2D1A/SLAM-associated protein (SAP) and X-linked inhibitor of apoptosis protein (XIAP) genes, respectively. The diagnosis of XLP in individuals with EBV-associated HLH (EBV-HLH) is generally difficult because they show basically similar symptoms to sporadic EBV-HLH. Although EBV-infected cells in sporadic EBV-HLH are known to be mainly in CD8+ T cells, the cell-type of EBV-infected cells in EBV-HLH seen in XLP patients remains undetermined.MethodsEBV-infected cells in two patients (XLP-1 and XLP-2) presenting EBV-HLH were evaluated by in EBER-1 in situ hybridization or quantitative PCR methods.ResultsBoth XLP patients showed that the dominant population of EBV-infected cells was CD19+ B cells, whereas EBV-infected CD8+ T cells were very few.ConclusionsIn XLP-related EBV-HLH, EBV-infected cells appear to be predominantly B cells. B cell directed therapy such as rituximab may be a valuable option in the treatment of EBV-HLH in XLP patients.

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Successful treatment of acute Epstein–Barr virus infection associated with X‐linked lymphoproliferative disorder with rituximab

Cited by 10 publications

References 3 publications

2B4-SAP signaling is required for the priming of naive CD8⁺ T cells by antigen-expressing B cells and B lymphoma cells

2B4-SAP signaling is required for the priming of naive CD8⁺ T cells by antigen-expressing B cells and B lymphoma cells

Practice parameter for the diagnosis and management of primary immunodeficiency

Characterization of Epstein-Barr virus (EBV)-infected cells in EBV-associated hemophagocytic lymphohistiocytosis in two patients with X-linked lymphoproliferative syndrome type 1 and type 2

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Successful treatment of acute Epstein–Barr virus infection associated with X‐linked lymphoproliferative disorder with rituximab

Cited by 10 publications

References 3 publications

2B4-SAP signaling is required for the priming of naive CD8+ T cells by antigen-expressing B cells and B lymphoma cells

2B4-SAP signaling is required for the priming of naive CD8+ T cells by antigen-expressing B cells and B lymphoma cells

Practice parameter for the diagnosis and management of primary immunodeficiency

Characterization of Epstein-Barr virus (EBV)-infected cells in EBV-associated hemophagocytic lymphohistiocytosis in two patients with X-linked lymphoproliferative syndrome type 1 and type 2

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2B4-SAP signaling is required for the priming of naive CD8⁺ T cells by antigen-expressing B cells and B lymphoma cells

2B4-SAP signaling is required for the priming of naive CD8⁺ T cells by antigen-expressing B cells and B lymphoma cells