title: B-cell deficiency and severe autoimmunity caused by deficiency of protein kinase C δ.
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 δ (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.
authors: CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, Vienna, Austria.
authors: Elisabeth
authors: E
authors: Salzer
authors: Elisangela
authors: E
authors: Santos-Valente
authors: Stefanie
authors: S
authors: Klaver
authors: Sol A
authors: SA
authors: Ban
authors: Wolfgang
authors: W
authors: Emminger
authors: Nina Kathrin
authors: NK
authors: Prengemann
authors: Wojciech
authors: W
authors: Garncarz
authors: Leonhard
authors: L
authors: Müllauer
authors: Renate
authors: R
authors: Kain
authors: Heidrun
authors: H
authors: Boztug
authors: Andreas
authors: A
authors: Heitger
authors: Klaus
authors: K
authors: Arbeiter
authors: Franz
authors: F
authors: Eitelberger
authors: Markus G
authors: MG
authors: Seidel
authors: Wolfgang
authors: W
authors: Holter
authors: Arnold
authors: A
authors: Pollak
authors: Winfried F
authors: WF
authors: Pickl
authors: Elisabeth
authors: E
authors: Förster-Waldl
authors: Kaan
authors: K
authors: Boztug
mesh_terms: D000328:Adult; D018941:Antigens, CD19 / Q000276:immunology; D015551:Autoimmunity; D001402:B-Lymphocytes / Q000276:immunology / Q000378:metabolism / Q000473:pathology*; D002648:Child; D005260:Female; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology; D007075:Immunoglobulin M / Q000276:immunology; D007153:Immunologic Deficiency Syndromes / Q000235:genetics* / Q000276:immunology / Q000473:pathology* / Q000628:therapy; D016130:Immunophenotyping; D008297:Male; D009154:Mutation; D010375:Pedigree; D020641:Polymorphism, Single Nucleotide; D020033:Protein Isoforms / Q000235:genetics / Q000276:immunology; D051745:Protein Kinase C-delta / Q000235:genetics* / Q000276:immunology
chemical_list: D018941:Antigens, CD19; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D020033:Protein Isoforms; D051745:Protein Kinase C-delta