B-cell deficiency and severe autoimmunity caused by deficiency of protein kinase C δ.
作者： Elisabeth Salzer , Elisangela Santos-Valente , Stefanie Klaver , Sol A. Ban , Wolfgang Emminger
DOI: 10.1182/BLOOD-2012-10-460741
关键词: Interleukin 、 Immunology 、 Immunophenotyping 、 Autoimmunity 、 CD19 、 Exome sequencing 、 Protein kinase C 、 Biology 、 PRKCD 、 Protein C
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 patients. In this study, we investigated patient from consanguineous family suffering recurrent infections and severe lupuslike autoimmunity. Immunophenotyping revealed progressive decrease CD19(+) B cells, defective class switch indicated by low numbers IgM- IgG-memory as well increased CD21(low) cells. Combined homozygosity mapping exome sequencing identified biallelic splice-site mutation protein C kinase δ (PRKCD), absence corresponding product. Consequently, phosphorylation myristoylated alanine-rich substrate was decreased, mRNA levels nuclear factor interleukin (IL)-6 IL-6 were increased. Our study uncovers human PRKCD deficiency novel cause common variable immunodeficiency-like
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