Combined immunodeficiency and Epstein-Barr virus-induced B cell malignancy in humans with inherited CD70 deficiency

被引：118

作者：

Abolhassani, Hassan ^{[1
,3
]}

Edwards, Emily S. J. ^{[4
,5
]}

Ikinciogullari, Aydan ^{[6
]}

Jing, Huie ^{[8
,9
]}

Borte, Stephan ^{[12
]}

Buggert, Marcus ^{[2
,13
]}

Du, Likun ^{[1
]}

Matsuda-Lennikov, Mami ^{[9
,10
]}

Romano, Rosa ^{[1
]}

Caridha, Rozina ^{[1
]}

Bade, Sangeeta ^{[8
,9
]}

Zhang, Yu ^{[8
,9
]}

Frederiksen, Juliet ^{[14
]}

Fang, Mingyan ^{[1
]}

Bal, Sevgi Kostel ^{[6
]}

Haskologlu, Sule ^{[6
]}

Dogu, Figen ^{[6
]}

Tacyildiz, Nurdan ^{[7
]}

Matthews, Helen F. ^{[8
,9
]}

McElwee, Joshua J. ^{[15
]}

Gostick, Emma ^{[16
]}

Price, David A. ^{[11
,16
]}

Palendira, Umaimainthan ^{[17
]}

Aghamohammadi, Asghar ^{[3
,18
]}

Boisson, Bertrand ^{[19
,20
,22
]}

Rezaei, Nima ^{[3
,18
]}

Karlsson, Annika C. ^{[2
]}

Lenardo, Michael J. ^{[9
]}

Casanova, Jean-Laurent ^{[19
,20
,21
,22
,23
]}

Hammarstrom, Lennart ^{[1
]}

Tangye, Stuart G. ^{[4
,5
]}

Su, Helen C. ^{[8
,9
]}

Pan-Hammarstrom, Qiang ^{[1
]}

机构：

[1] Karolinska Univ, Huddinge Hosp, Karolinska Inst, Div Clin Immunol,Dept Lab Med, SE-1418 Stockholm, Sweden

[2] Karolinska Univ, Huddinge Hosp, Karolinska Inst, Div Clin Microbiol,Dept Lab Med, SE-1418 Stockholm, Sweden

[3] Univ Tehran Med Sci, Res Ctr Immunodeficiencies, Childrens Med Ctr, Tehran 14149, Iran

[4] Garvan Inst Med Res, Div Immunol, Darlinghurst, NSW 2010, Australia

[5] Univ New South Wales, St Vincents Clin Sch, Fac Med, Darlinghurst, NSW 2010, Australia

[6] Ankara Univ, Sch Med, Dept Pediat Immunol & Allergy, TR-06100 Dikimevi Ankara, Turkey

[7] Ankara Univ, Sch Med, Dept Pediat Hematol & Oncol, TR-06100 Dikimevi Ankara, Turkey

[8] NIAID, Lab Host Def, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA

[9] NIAID, Clin Genom Program, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA

[10] NIAID, Lab Immunol, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA

[11] NIAID, Vaccine Res Ctr, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA

[12] Hosp St Georg Leipzig, ImmunoDeficiency Ctr Leipzig, D-04129 Leipzig, Germany

[13] Univ Penn, Dept Microbiol, Philadelphia, PA 19104 USA

[14] Tech Univ Denmark, Dept Syst Biol, DK-2800 Lyngby, Denmark

[15] Merck & Co Inc, Merck Res Labs, Boston, MA 02115 USA

[16] Cardiff Univ, Sch Med, Div Infect & Immun, Cardiff CF14 4XN, S Glam, Wales

[17] Univ Sydney, Centenary Inst, Newtown, NSW 2042, Australia

[18] Univ Sci Educ & Res Network, Primary Immunodeficiency Dis Network, Tehran 14149, Iran

[19] Rockefeller Univ, St Giles Lab Human Genet Infect Dis, New York, NY 10065 USA

[20] Necker Hosp Sick Children, INSERM, Lab Human Genet Infect Dis, U 1163, F-75015 Paris, France

[21] Necker Hosp Sick Children, Pediat Hematol Immunol Unit, F-75015 Paris, France

[22] Paris Descartes Univ, Imagine Inst, F-75015 Paris, France

[23] Howard Hughes Med Inst, New York, NY 10065 USA

来源：

JOURNAL OF EXPERIMENTAL MEDICINE | 2017年 / 214卷 / 01期

基金：

英国医学研究理事会; 美国国家卫生研究院; 瑞典研究理事会;

关键词：

COMMON VARIABLE IMMUNODEFICIENCY; T-CELL; CD27/CD70; INTERACTION; ADAPTIVE RESPONSES; CD27; DEFICIENCY; IN-VIVO; INFECTION; NK; GENERATION; DISEASE;

D O I：

10.1084/jem.20160849

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

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.

引用

页码：91 / 106

页数：16

共 55 条

[1] A hypomorphic recombination-activating gene 1 (RAG1) mutation resulting in a phenotype resembling common variable immunodeficiency [J].