ArticleBlood2013
Loss-of-function of the protein kinase C δ (PKCδ) causes a B-cell lymphoproliferative syndrome in humans.
Article in Blood, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 78 papers, 1 of them a synthesis that pooled it.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
78 citing papers in PubMed, 1 synthesis or guideline pooled it, 139 citations in OpenAlex.
- Primary Immune Regulatory Disorders With an Autoimmune Lymphoproliferative Syndrome-Like Phenotype: Immunologic Evaluation, Early Diagnosis and Management.Frontiers in immunology · 2021Pooled it
- Human inborn errors of the phagocyte respiratory burst: Chronic granulomatous disease and beyond.Journal of human immunity · 2026Article
- Steroid receptor coactivators in immunity - From function to emerging translational opportunities.The Journal of biological chemistry · 2026Review
- CD20 tails interact with the 14-3-3/GEF-H1 complex and microtubule network upon PKCδ phosphorylation.The EMBO journal · 2026Article
- Expanding the scope of PI3K-δ inhibition: Leniolisib treatment in PRKCD deficiency.Journal of human immunity · 2026Article
- Dynamic feedback control of oncogenic tyrosine kinase signaling in acute leukemia.Science signaling · 2026Article
- Restoring B cell intrinsic tolerance to lupus autoimmunity: a rational strategy for lupus treatment.Frontiers in immunology · 2026Review
- Human genetic influences on early B cell development.Journal of human immunity · 2025Review
- How (Ultra-)Rare Gene Variants Improve Our Understanding of More Common Autoimmune and Inflammatory Diseases.ACR open rheumatology · 2025Review
- Chronic granulomatous disease: lessons in cell biology from monogenic immunodeficiency.Clinical and experimental immunology · 2025Review
- Case Report: Clinical, molecular, and functional characterization of autoimmune lymphoproliferative syndrome-a family study with a multimodal diagnosis.Frontiers in pediatrics · 2025Article
- PKCδ Protects against Lupus Autoimmunity.Biomedicines · 2024Review
- Seropositive polyarthritis and diffuse lymphadenopathy associated with PRKCD mutation.Rheumatology (Oxford, England) · 2024Article
- Mendelian Causes of Autoimmunity: the Lupus Phenotype.Journal of clinical immunology · 2024Review
- Cytokine Storm Syndromes Associated with Epstein-Barr Virus.Advances in experimental medicine and biology · 2024Review
- PKCδ regulates the vascular biology in diabetic atherosclerosis.Cell communication and signaling : CCS · 2023Review
- Phenotypic Variability in PRKCD: a Review of the Literature.Journal of clinical immunology · 2023Review
- Signaling Pathways Leading to mTOR Activation Downstream Cytokine Receptors in Lymphocytes in Health and Disease.International journal of molecular sciences · 2023Review
- Compound Heterozygous Mutations in PRKCD Associated with Early-Onset Lupus and Severe and Invasive Infections in Siblings.Journal of clinical immunology · 2023Article
- Identification of novel NFKB1 and ICOS frameshift variants in patients with CVID.Clinical and experimental immunology · 2023Article
18 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
14 authors at 5 institutions in 2 countries.
Funding
Abstract
Defective lymphocyte apoptosis results in chronic lymphadenopathy and/or splenomegaly associated with autoimmune phenomena. The prototype for human apoptosis disorders is the autoimmune lymphoproliferative syndrome (ALPS), which is caused by mutations in the FAS apoptotic pathway. Recently, patients with an ALPS-like disease called RAS-associated autoimmune leukoproliferative disorder, in which somatic mutations in NRAS or KRAS are found, also were described. Despite this progress, many patients with ALPS-like disease remain undefined genetically. We identified a homozygous, loss-of-function mutation in PRKCD (PKCδ) in a patient who presented with chronic lymphadenopathy, splenomegaly, autoantibodies, elevated immunoglobulins and natural killer dysfunction associated with chronic, low-grade Epstein-Barr virus infection. This mutation markedly decreased protein expression and resulted in ex vivo B-cell hyperproliferation, a phenotype similar to that of the PKCδ knockout mouse. Lymph nodes showed intense follicular hyperplasia, also mirroring the mouse model. Immunophenotyping of circulating lymphocytes demonstrated expansion of CD5+CD20+ B cells. Knockdown of PKCδ in normal mononuclear cells recapitulated the B-cell hyperproliferative phenotype in vitro. Reconstitution of PKCδ in patient-derived EBV-transformed B-cell lines partially restored phorbol-12-myristate-13-acetate-induced cell death. In summary, homozygous PRKCD mutation results in B-cell hyperproliferation and defective apoptosis with consequent lymphocyte accumulation and autoantibody production in humans, and disrupts natural killer cell function.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.