B-cell deficiency and severe autoimmunity caused by deficiency of protein kinase C δ

被引：95

作者：

Salzer, Elisabeth ^{[1
]}

Santos-Valente, Elisangela ^{[1
]}

Klaver, Stefanie ^{[1
,2
]}

Ban, Sol A. ^{[1
]}

Emminger, Wolfgang ^{[3
]}

Prengemann, Nina Kathrin ^{[1
]}

Garncarz, Wojciech ^{[1
]}

Muellauer, Leonhard ^{[4
]}

Kain, Renate ^{[4
]}

Boztug, Heidrun ^{[5
,6
]}

Heitger, Andreas ^{[5
,6
]}

Arbeiter, Klaus ^{[3
]}

Eitelberger, Franz

Seidel, Markus G. ^{[5
,6
]}

Holter, Wolfgang ^{[5
,6
]}

Pollak, Arnold ^{[3
]}

Pickl, Winfried F. ^{[7
,8
]}

Foerster-Waldl, Elisabeth ^{[3
]}

Boztug, Kaan ^{[1
,3
]}

机构：

[1] Austrian Acad Sci, CeMM Res Ctr Mol Med, A-1010 Vienna, Austria

[2] Univ Sao Paulo, Inst Ciencias Biomed, BR-05508 Sao Paulo, Brazil

[3] Med Univ Vienna, Dept Pediat & Adolescent Med, A-1090 Vienna, Austria

[4] Med Univ Vienna, Clin Inst Pathol, A-1090 Vienna, Austria

[5] Med Univ Vienna, Dept Pediat, St Anna Kinderspital, A-1090 Vienna, Austria

[6] Med Univ Vienna, Childrens Canc Res Inst, A-1090 Vienna, Austria

[7] Med Univ Vienna, Christian Doppler Lab Immunomodulat, A-1090 Vienna, Austria

[8] Med Univ Vienna, Inst Immunol, Ctr Pathophysiol Infectiol & Immunol, A-1090 Vienna, Austria

来源：

BLOOD | 2013年 / 121卷 / 16期

基金：

奥地利科学基金会;

关键词：

MARCKS; GENE; IMMUNODEFICIENCY; POLYMORPHISM; DISEASE; PLCG2; CTLA4;

D O I：

10.1182/blood-2012-10-460741

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

Primary B-cell disorders comprise a heterogeneous group of inherited immunodeficiencies, often associated with autoimmunity causing significant morbidity. The underlying genetic etiology remains elusive in the majority of patients. In this study, we investigated a patient from a consanguineous family suffering from recurrent infections and severe lupuslike autoimmunity. Immunophenotyping revealed progressive decrease of CD19(+) B cells, a defective class switch indicated by low numbers of IgM- nd IgG-memory B cells, as well as increased numbers of CD21(low) B cells. Combined homozygosity mapping and exome sequencing identified a biallelic splicesite mutation in protein C kinase delta (PRKCD), causing the absence of the corresponding protein product. Consequently, phosphorylation of myristoylated alanine-rich C kinase substrate was decreased, and mRNA levels of nuclear factor interleukin (IL)-6 and IL-6 were increased. Our study uncovers human PRKCD deficiency as a novel cause of common variable immunodeficiency-like B-cell deficiency with severe autoimmunity.

引用

页码：3112 / 3116

页数：5

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