ArticleThe Journal of allergy and clinical immunology2024
PLCG2-associated immune dysregulation (PLAID) comprises broad and distinct clinical presentations related to functional classes of genetic variants.
Article in The Journal of allergy and clinical immunology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
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Who cites it
34 citing papers in PubMed, 47 citations in OpenAlex.
- Gut microbiota-activated PLCγ2 monocytes drive atrial fibrillation.Nature communications · 2026Article
- Review
- Decoding variants of uncertain significance in systemic autoinflammatory diseases.Nature reviews. Rheumatology · 2026Review
- Genetic mutations in primary and metastatic tumors of a rare mixed neuroendocrine carcinoma and high-grade serous ovarian cancer.Medical molecular morphology · 2026Article
- Behçet's spectrum disorders: genetic and immunological insights into an emerging disease concept.World journal of pediatrics : WJP · 2026Review
- PLCG2 signaling and genetic resilience in Alzheimer's disease.Molecular neurodegeneration · 2026Review
- Clinical characterization and targeted genetic mutation profiling of autoimmune disease-associated B-cell lymphoma.Discover oncology · 2026Article
- Current perspectives of host-pathogen dynamics in coccidioidomycosis.Current opinion in microbiology · 2026Review
- Protective PLCG2 variants associate with a delayed onset of Alzheimer's disease among heterozygous APOE ε4 carriers.Alzheimer's research & therapy · 2026Article
- PLCG2 across human disease: genetic variants, signaling mechanisms, and clinical implications.Journal of translational medicine · 2026Review
- Bioinformatics analysis of potential molecular markers and immunological characteristics shared between post-treatment Lyme disease syndrome and rheumatoid arthritis.Frontiers in immunology · 2026Article
- Whole Exome Sequencing in Children With Autoimmune Hepatitis Identified Mutations in Genes Involved in the mTORC1 Signaling Pathway.Gastro hep advances · 2026Article
- Recent variant discoveries and emerging genetic mechanisms in autoinflammatory diseases.Frontiers in immunology · 2026Review
- Identification of Renal Transcripts Associated with Kidney Function and Prognosis in ANCA-Associated Vasculitis.Journal of the American Society of Nephrology : JASN · 2026Article
- Cold-Induced Urticarias with Familial Background: Clinical Spectrum, Pathogenesis, and Diagnostic Challenges.Diagnostics (Basel, Switzerland) · 2025Review
- Overlap of familial Mediterranean fever and APLAID treated with anakinra: a case-based review.Clinical rheumatology · 2025Review
- Early-onset systemic lupus erythematosus in a patient with an inborn error of immunity caused by a NRAS mutation and treated with telitacicept.Molecular and cellular pediatrics · 2025Article
- Update on new autoinflammatory disorders from the 2024 Pediatric Rheumatology European Society Congress.Pediatric rheumatology online journal · 2025Review
- In Silico Analysis of MiRNA Regulatory Networks to Identify Potential Biomarkers for the Clinical Course of Viral Infections.International journal of molecular sciences · 2025Article
- Resistance to targeted therapies in chronic lymphocytic leukemia: Current status and perspectives for clinical and diagnostic practice.Leukemia · 2025Review
Corrections and comments
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Authors and funding
11 authors at 3 institutions in 1 country.
Funding
Abstract
backgroundPathogenic variants of phospholipase C gamma 2 (PLCG2) cause 2 related forms of autosomal-dominant immune dysregulation (ID), PLCγ2-associated antibody deficiency and immune dysregulation (PLAID) and autoinflammatory PLAID (APLAID). Since describing these conditions, many PLCG2 variants of uncertain significance have been identified by clinical sequencing of patients with diverse features of ID.
objectiveWe sought to functionally classify PLCG2 variants and explore known and novel genotype-function-phenotype relationships.
methodsClinical data from patients with PLCG2 variants were obtained via standardized questionnaire. PLCG2 variants were generated by mutagenesis of enhanced green fluorescent protein (EGFP)-PLCG2 plasmid, which was overexpressed in Plcg2-deficient DT-40 B cells. B-cell receptor-induced calcium flux and extracellular signal-regulated kinase phosphorylation were assayed by flow cytometry. In some cases, stimulation-induced calcium flux was also measured in primary patient cells.
resultsThree-fourths of PLCG2 variants produced functional alteration of B-cell activation, in vitro. Thirteen variants led to gain of function (GOF); however, most functional variants defined a new class of PLCG2 mutation, monoallelic loss of function (LOF). Susceptibility to infection and autoinflammation were common with both GOF and LOF variants, whereas a new phenotypic cluster consisting of humoral immune deficiency, autoinflammation, susceptibility to herpesvirus infection, and natural killer cell dysfunction was observed in association with multiple heterozygous LOF variants detected in both familial and sporadic cases. In some cases, PLCG2 variants produced greater effects in natural killer cells than in B cells.
conclusionsThis work expands the genotypic and phenotypic associations with functional variation in PLCG2, including a novel form of ID in carriers of heterozygous loss of PLCG2 function. It also demonstrates the need for more diverse assays for assessing the impact of PLCG2 variants on human disease.
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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 Socratic graph.