ArticleJournal of clinical immunology2020
Severe Autoinflammatory Manifestations and Antibody Deficiency Due to Novel Hypermorphic PLCG2 Mutations.
Article in Journal of clinical immunology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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Who cites it
30 citing papers in PubMed, 58 citations in OpenAlex.
- 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
- 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
- Case Report:Frontiers in immunology · 2025Article
- The crystal and cryo-EM structures of PLCγ2 reveal dynamic interdomain recognitions in autoinhibition.Science advances · 2024Article
- APLAID complicated with arrhythmogenic dilated cardiomyopathy caused by a novel PLCG2 variant.Immunologic research · 2024Article
- A guide to selecting high-performing antibodies for PLC-gamma-2 for use in Western Blot, immunoprecipitation and immunofluorescence.F1000Research · 2024Article
- PLCG2-associated immune dysregulation (PLAID) comprises broad and distinct clinical presentations related to functional classes of genetic variants.The Journal of allergy and clinical immunology · 2024Article
- A novel fluorogenic reporter substrate for 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-2 (PLCγ2): Application to high-throughput screening for activators to treat Alzheimer's disease.SLAS discovery : advancing life sciences R & D · 2023Article
- Activation Mechanisms and Diverse Functions of Mammalian Phospholipase C.Biomolecules · 2023Review
- G-CSF drives autoinflammation in APLAID.Nature immunology · 2023Article
- Targeting G-CSF to treat autoinflammation.Nature immunology · 2023Article
- Ten things to know about NLRP10.Nature immunology · 2023Article
- Clinical and immunological features of an APLAID patient caused by a novel mutation inFrontiers in immunology · 2023Article
- Inflammasome activation and formation of ASC specks in patients with juvenile idiopathic arthritis.Frontiers in medicine · 2023Article
- Tailored treatments in inborn errors of immunity associated with atopy (IEIs-A) with skin involvement.Frontiers in pediatrics · 2023Review
- Review
- Pathophysiology, clinical manifestations and current management of IL-1 mediated monogenic systemic autoinflammatory diseases, a literature review.Pediatric rheumatology online journal · 2022Review
- Src-related thrombocytopenia: a fine line between a megakaryocyte dysfunction and an immune-mediated disease.Blood advances · 2022Article
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Authors and funding
30 authors at 13 institutions in 2 countries.
Funding
Abstract
Autoinflammatory diseases (AIDs) were first described as clinical disorders characterized by recurrent episodes of seemingly unprovoked sterile inflammation. In the past few years, the identification of novel AIDs expanded their phenotypes toward more complex clinical pictures associating vasculopathy, autoimmunity, or immunodeficiency. Herein, we describe two unrelated patients suffering since the neonatal period from a complex disease mainly characterized by severe sterile inflammation, recurrent bacterial infections, and marked humoral immunodeficiency. Whole-exome sequencing detected a novel, de novo heterozygous PLCG2 variant in each patient (p.Ala708Pro and p.Leu845_Leu848del). A clear enhanced PLCγ2 activity for both variants was demonstrated by both ex vivo calcium responses of the patient's B cells to IgM stimulation and in vitro assessment of PLC activity. These data supported the autoinflammation and PLCγ2-associated antibody deficiency and immune dysregulation (APLAID) diagnosis in both patients. Immunological evaluation revealed a severe decrease of immunoglobulins and B cells, especially class-switched memory B cells, with normal T and NK cell counts. Analysis of bone marrow of one patient revealed a reduced immature B cell fraction compared with controls. Additional investigations showed that both PLCG2 variants activate the NLRP3-inflammasome through the alternative pathway instead of the canonical pathway. Collectively, the evidences here shown expand APLAID diversity toward more severe phenotypes than previously reported including dominantly inherited agammaglobulinemia, add novel data about its genetic basis, and implicate the alternative NLRP3-inflammasome activation pathway in the basis of sterile inflammation.
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