B-cell deficiency and severe autoimmunity caused by deficiency of protein kinase C delta.
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Salzer E, Santos-Valente E, Klaver S, Ban SA, Emminger W, Prengemann NK, Garncarz W, Mullauer L, Kain R, Boztug H, Heitger A, Arbeiter K, Eitelberger F, Seidel MG, Holter W, Pollak A, Pickl WF, Forster-Waldl E, Boztug K
B-cell deficiency and severe autoimmunity caused by deficiency of protein kinase C delta.
Blood. 2013 Apr 18;121(16):3112-6. doi: 10.1182/blood-2012-10-460741. Epub 2013 Jan 14.
- PubMed ID
- 23319571 [ View in PubMed]
- Abstract
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- and IgG-memory B cells, as well as increased numbers of CD21(low) B cells. Combined homozygosity mapping and exome sequencing identified a biallelic splice-site 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.