Abolhassani, Hassan, Edwards, Emily S.J., Ikinciogullari, Aydan, Jing, Huie, Borte, Stephan, Buggert, Marcus, Du, Likun, Matsuda-Lennikov, Mami, Romano, Rosa, Caridha, Rozina, Bade, Sangeeta, Zhang, Yu, Frederiksen, Juliet, Fang, Mingyan, Bal, Sevgi Kostel, Haskologlu, Sule, Dogu, Figen, Tacyildiz, Nurdan, Matthews, Helen F., McElwee, Joshua J., Gostick, Emma, Price, David  ORCID: https://orcid.org/0000-0001-9416-2737, Palendira, Umaimainthan, Aghamohammadi, Asghar, Boisson, Bertrand, Rezaei, Nima, Karlsson, Annika C., Lenardo, Michael J., Casanova, Jean-Laurent, Hammarström, Lennart, Tangye, Stuart G., Su, Helen C. and Pan-Hammarström, Qiang
2017.
Combined immunodeficiency and Epstein-Barr virus-induced B cell malignancy in humans with inherited CD70 deficiency.
Journal of Experimental Medicine
214
(1)
, p. 91.
10.1084/jem.20160849
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Abstract
In this study, we describe four patients from two unrelated families of different ethnicities with a primary immunodeficiency, predominantly manifesting as susceptibility to Epstein-Barr virus (EBV)–related diseases. Three patients presented with EBV-associated Hodgkin’s lymphoma and hypogammaglobulinemia; one also had severe varicella infection. The fourth had viral encephalitis during infancy. Homozygous frameshift or in-frame deletions in CD70 in these patients abolished either CD70 surface expression or binding to its cognate receptor CD27. Blood lymphocyte numbers were normal, but the proportions of memory B cells and EBV-specific effector memory CD8+ T cells were reduced. Furthermore, although T cell proliferation was normal, in vitro–generated EBV-specific cytotoxic T cell activity was reduced because of CD70 deficiency. This reflected impaired activation by, rather than effects during killing of, EBV-transformed B cells. Notably, expression of 2B4 and NKG2D, receptors implicated in controlling EBV infection, on memory CD8+ T cells from CD70-deficient individuals was reduced, consistent with their impaired killing of EBV-infected cells. Thus, autosomal recessive CD70 deficiency is a novel cause of combined immunodeficiency and EBV-associated diseases, reminiscent of inherited CD27 deficiency. Overall, human CD70–CD27 interactions therefore play a nonredundant role in T and B cell–mediated immunity, especially for protection against EBV and humoral immunity.
| Item Type: | Article |
|---|---|
| Date Type: | Publication |
| Status: | Published |
| Schools: | Schools > Medicine |
| Subjects: | R Medicine > R Medicine (General) |
| Publisher: | Rockefeller University Press |
| ISSN: | 0022-1007 |
| Date of First Compliant Deposit: | 31 January 2017 |
| Date of Acceptance: | 7 December 2016 |
| Last Modified: | 05 May 2023 18:12 |
| URI: | https://orca.cardiff.ac.uk/id/eprint/97895 |
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