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

Elisabeth Salzer, Elisangela Santos-Valente, Stefanie Klaver, Sol A. Ban, Wolfgang Emminger, Nina Kathrin Prengemann, Wojciech Garncarz, Leonhard Müllauer, Renate Kain, Heidrun Boztug, Andreas Heitger, Klaus Arbeiter, Franz Eitelberger, Markus G. Seidel, Wolfgang Holter, Arnold Pollak, Winfried F. Pickl, Elisabeth Förster-Waldl and Kaan Boztug

Key points

  • 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.