2023
PLCG2-associated immune dysregulation (PLAID) comprises broad and distinct clinical presentations related to functional classes of genetic variants
Baysac K, Sun G, Nakano H, Schmitz E, Cruz A, Fisher C, Bailey A, Group P, Abbott J, Becerra J, Allenspach E, Assing K, Atkinson T, Bargir U, Baxter S, Bergerson J, Bista R, Blanche S, Buckley L, Butte M, Carcamo B, Chandrakala S, Chen K, Chervinskiy S, Chinn I, Chong H, Coffey K, Copland A, Cowen E, Cros G, De Bruycker J, de la Morena M, Ehlayel M, Satter L, Gelfand E, Gilliaux O, Glover S, Gorman M, Griffin T, Grimbacher B, Gru A, Haddad E, Hadjadj J, Hajjar J, Hauck F, Hautala T, Holland S, Hsieh E, Hsu F, Jacquemin E, Jindal A, Kahn S, Keller M, Kobayashi R, Krupski C, Larkin A, Lawrence M, Madkaikar M, Malphettes M, Martelius, Mehta M, Metcalfe D, Meyts I, Nannapaneni N, Vinyals J, Olivier K, Ombrello A, Orange J, Rabinovitch N, Rauscher C, Redfern A, Reynolds P, Rieux-Laucat F, Secord E, Seeborg F, Seppänen M, Sereti I, Shin D, Shin J, Snapper S, Suri D, Tangcheewinsirikul S, Thatayatikom A, Torgerson T, Touzot F, Uzel G, Varjosalo M, Vasconcelos D, von Bernuth H, Walsh T, Walter J, Ward B, Wittkowski H, Wysocki C, Mace E, Milner J, Ombrello M. PLCG2-associated immune dysregulation (PLAID) comprises broad and distinct clinical presentations related to functional classes of genetic variants. Journal Of Allergy And Clinical Immunology 2023, 153: 230-242. PMID: 37769878, PMCID: PMC11337301, DOI: 10.1016/j.jaci.2023.08.036.Peer-Reviewed Original ResearchConceptsImmune dysregulationPhospholipase C gamma 2Gain of functionB cellsNatural killer cell dysfunctionCalcium fluxLoF variantsNatural killer cellsHumoral immune deficiencyDistinct clinical presentationsPrimary patient cellsExtracellular signal-regulated kinase (ERK) phosphorylationB cell activationSignal-regulated kinase phosphorylationPLCG2 mutationsAntibody deficiencyKiller cellsClinical presentationImmune deficiencyCell dysfunctionClinical dataStandardized questionnaireFunctional alterationsSporadic casesPathogenic variants
2022
Defining Clinical and Immunological Predictors of Poor Immune Responses to COVID-19 mRNA Vaccines in Patients with Primary Antibody Deficiency
Shin JJ, Par-Young J, Unlu S, McNamara A, Park HJ, Shin MS, Gee RJ, Doyle H, Afinogenova Y, Zidan E, Kwah J, Russo A, Mamula M, Hsu FI, Catanzaro J, Racke M, Bucala R, Wilen C, Kang I. Defining Clinical and Immunological Predictors of Poor Immune Responses to COVID-19 mRNA Vaccines in Patients with Primary Antibody Deficiency. Journal Of Clinical Immunology 2022, 42: 1137-1150. PMID: 35713752, PMCID: PMC9203263, DOI: 10.1007/s10875-022-01296-4.Peer-Reviewed Original ResearchMeSH KeywordsAntibodies, ViralCD8-Positive T-LymphocytesCommon Variable ImmunodeficiencyCOVID-19COVID-19 VaccinesHumansImmunity, CellularImmunoglobulin AImmunoglobulin GMRNA VaccinesPrimary Immunodeficiency DiseasesRNA, MessengerSARS-CoV-2Spike Glycoprotein, CoronavirusVaccinationVaccinesVaccines, SyntheticConceptsCommon variable immune deficiencyT cellsImmune responseIgG responsesCVID patientsMRNA vaccinesB cellsCoronavirus disease 2019 (COVID-19) mRNA vaccinesCOVID-19 mRNA vaccinesBaseline immune profileHistory of autoimmunityPrimary antibody deficiencyT cell responsesCellular immune responsesPoor immune responseVariable immune deficiencyMemory B cellsSARS-CoV-2 spike proteinBaseline IgGCVID diagnosisEM CD8Immunological predictorsPAD cohortSpecific CD4Immune profile
2018
Patients with common variable immunodeficiency with autoimmune cytopenias exhibit hyperplastic yet inefficient germinal center responses
Romberg N, Le Coz C, Glauzy S, Schickel JN, Trofa M, Nolan BE, Paessler M, Xu M, Lambert MP, Lakhani SA, Khokha MK, Jyonouchi S, Heimall J, Takach P, Maglione PJ, Catanzaro J, Hsu FI, Sullivan KE, Cunningham-Rundles C, Meffre E. Patients with common variable immunodeficiency with autoimmune cytopenias exhibit hyperplastic yet inefficient germinal center responses. Journal Of Allergy And Clinical Immunology 2018, 143: 258-265. PMID: 29935219, PMCID: PMC6400323, DOI: 10.1016/j.jaci.2018.06.012.Peer-Reviewed Original ResearchConceptsCommon variable immunodeficiencyVariable immunodeficiencyB cellsCommensal bacteriaIsotype-switched memory B cellsRegulatory T cell frequencyFollicular helper T cellsGC responseIsotype-switched antibodiesT cell frequenciesSubset of patientsT cell compartmentHelper T cellsPeripheral blood samplesMemory B cellsGerminal center responseB cell clonesAutoimmune cytopeniasGC hyperplasiaSerum endotoxemiaExcisional lymphAntibody responseT cellsMucosal microbiotaSomatic hypermutation frequencies