Recurrent inflammatory disease caused by a heterozygous mutation in CD48

Volkmer, Benjamin; Planas, Raquel; Gossweiler, Emanuel; Lünemann, Anna; Opitz, Lennart; Mauracher, Andrea A.; Nüesch, Ursina; Gayden, Tenzin; Kaiser, Daniela; Drexel, Barbara; Dumrese, Claudia; Jabado, Nada; Vavassori, Stefano; Schmid, Jana Pachlopnik

doi:10.1016/j.jaci.2019.07.038

Cited by 13 publications

(15 citation statements)

References 21 publications

(23 reference statements)

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“…30 Variants in other genes (SH2D1A, CD48, BIRC4, NLRC4, HAVCR2 [TIM-3], CDC42, RC3H1, HEM1, and AP3B3A) have been linked to HLH and HLH-like disease. [31][32][33][34][35][36] ZNFX1 must now be added to this list. Clinical observations in patients with ZNFX1 deficiency have revealed an interplay between inflammation and immunodeficiency.…”

Section: Discussionmentioning

confidence: 99%

Multisystem inflammation and susceptibility to viral infections in human ZNFX1 deficiency

Vavassori

Chou

Faletti

et al. 2021

Journal of Allergy and Clinical Immunology

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Section: Discussionmentioning

confidence: 99%

Multisystem inflammation and susceptibility to viral infections in human ZNFX1 deficiency

Vavassori

Chou

Faletti

et al. 2021

Journal of Allergy and Clinical Immunology

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“…Mutations in other genes (RAB27A, LYST, SH2D1A, BIRC4, HAVCR2 (TIM-3), NLRC4, CD48, CDC42, and AP3B3A) were shown to be responsible for primary immunodeficiency and autoinflammatory syndromes in which HLH is a prominent clinical feature. [3][4][5][6][7][8] Viral infections are important triggers of HLH episodes in patients with a genetic predisposition. Persistent, uncontrolled activation of innate and adaptive immunity in secondary lymphoid organs and liver with cytokine hypersecretion ultimately results in hemorrhage, multiorgan failure, and death.…”

Section: Introductionmentioning

confidence: 99%

Targeted busulfan-based reduced-intensity conditioning and HLA-matched HSCT cure hemophagocytic lymphohistiocytosis

et al. 2020

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Reduced-intensity/reduced-toxicity conditioning and allogeneic T-cell replete hematopoietic stem cell transplantation are curative in patients with hemophagocytic lymphohistiocytosis (HLH). Unstable donor chimerism (DC) and relapses are clinical challenges . We examined the effect of a reduced-intensity conditioning regimen based on targeted busulfan to enhance myeloid DC in HLH. The European Society for Bone and Marrow Transplantation–approved reduced-intensity conditioning protocol comprised targeted submyeloablative IV busulfan, IV fludarabine, and serotherapy comprising IV alemtuzumab (0.5-0.8 mg/kg) for unrelated-donor and IV rabbit anti–T-cell globulin for related-donor transplants. We assessed toxicity, engraftment, graft-versus-host disease (GHVD), DC in blood cell subtypes, and overall survival/event-free survival. Twenty-five patients from 7 centers were treated (median age, 0.68 year). The median total dose and cumulative area under the curve of busulfan was 13.1 mg/kg (6.4-26.4) and 63.1 mg/L × h (48-77), respectively. Bone marrow, peripheral blood stem cell, or cord blood transplants from HLA-matched related (n = 7) or unrelated (n = 18) donors were administered. Donor cells engrafted in all patients (median: neutrophils d+20/platelets d+28). At last follow-up (median, 36 months; range, 8-111 months), the median DC of CD15+ neutrophils, CD3+ T cells, and CD16+56+ natural killer cells was 99.5% (10-100), 97% (30-100), and 97.5% (30-100), respectively. Eight patients (32%) developed sinusoidal obstruction syndrome, resolving after defibrotide treatment. The 3-year overall survival and event-free survival rates were both 100%. None of the patients developed acute grade III to IV GHVD. Limited chronic GVHD was encountered in 4%. This regimen achieves excellent results with stable DC in patients with HLH.

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“… 37 Haploinsufficient expression of the 2B4 ligand CD48 leads also to HLH, even so in the sole so far described patient no involvement of EBV has been described so far. 82 The requirement of SAP for CD8 + T‐cell recognition of EBV‐infected B cells is also documented by findings that in female SAP/SH2D1A (HGNC: 10820) mutation carriers preferentially the defective X chromosome is condensed in EBV‐specific CD8 + T cells. 83 Furthermore, in XLP1 patients that manage to control EBV infection somatically SAP gene reverted CD8 + T cells specific for this tumor virus can be found.…”

Section: Costimulatory Receptors Of Cytotoxic Lymphocytes Required To...mentioning

confidence: 93%

“…Furthermore, 2B4 blocking with antibodies compromises CD8 + T cell‐mediated immune control of EBV in humanized mice 37 . Haploinsufficient expression of the 2B4 ligand CD48 leads also to HLH, even so in the sole so far described patient no involvement of EBV has been described so far 82 . The requirement of SAP for CD8 + T‐cell recognition of EBV‐infected B cells is also documented by findings that in female SAP/SH2D1A (HGNC: 10820) mutation carriers preferentially the defective X chromosome is condensed in EBV‐specific CD8 + T cells 83 .…”

Section: Costimulatory Receptors Of Cytotoxic Lymphocytes Required To...mentioning

confidence: 99%

Immune checkpoints in T cells during oncogenic γ‐herpesvirus infections

Münz

2022

Journal of Medical Virology

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Epstein–Barr virus (EBV) and Kaposi sarcoma‐associated herpesvirus (KSHV) are two persistent oncogenic γ‐herpesviruses with an exclusive tropism for humans. They cause cancers of lymphocyte, epithelial and endothelial cell origin, such as Burkitt's and Hodgkin's lymphoma, primary effusion lymphoma, nasopharyngeal carcinoma, and Kaposi sarcoma. Mutations in immune‐related genes but also adverse events during immune checkpoint inhibition in cancer patients have revealed molecular requirements for immune control of EBV and KSHV. These include costimulatory and coinhibitory receptors on T cells that are currently explored or already therapeutically targeted in tumor patients. This review discusses these co‐receptors and their influence on EBV‐ and KSHV‐associated diseases. The respective studies reveal surprising specificities of some of these receptors for immunity to these tumor viruses, benefits of their blockade for some but not other virus‐associated diseases, and that EBV‐ and KSHV‐specific immune control should be monitored during immune checkpoint inhibition to prevent adverse events that might be associated with their reactivation during treatment.

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Recurrent inflammatory disease caused by a heterozygous mutation in CD48

Cited by 13 publications

References 21 publications

Multisystem inflammation and susceptibility to viral infections in human ZNFX1 deficiency

Multisystem inflammation and susceptibility to viral infections in human ZNFX1 deficiency

Targeted busulfan-based reduced-intensity conditioning and HLA-matched HSCT cure hemophagocytic lymphohistiocytosis

Immune checkpoints in T cells during oncogenic γ‐herpesvirus infections

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