PRKCD deficiency causes a novel primary immunodeficiency with B cell deficiency and severe autoimmunity
Protein kinase C delta may represent a key factor controlling immune homeostasis and autoimmunity
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 lupus-like autoimmunity. Immunophenotyping revealed progressive decrease of CD19+ B cells, defective class switch indicated by low numbers of IgM- and IgG-memory B cells as well as increased numbers of CD21low B cells. Combined homozygosity mapping and exome sequencing identified a biallelic splice-site mutation in protein C kinase delta (PRKCD), causing absence of the corresponding protein product. Consequently, phosphorylation of myristoylated alanine-rich C kinase substrate (MARCKS) was decreased and mRNA levels of nuclear factor interleukin-6 (NF-IL6) and IL6 were increased. Our study uncovers human PRKCD deficiency as a novel cause of common variable immunodeficiency-like B cell deficiency with severe autoimmunity.
- Submitted October 10, 2012.
- Accepted December 28, 2012.
- Copyright © 2005 American Society of Hematology