2017
Effective “activated PI3Kδ syndrome”–targeted therapy with the PI3Kδ inhibitor leniolisib
Rao VK, Webster S, Dalm VASH, Šedivá A, van Hagen PM, Holland S, Rosenzweig SD, Christ AD, Sloth B, Cabanski M, Joshi AD, de Buck S, Doucet J, Guerini D, Kalis C, Pylvaenaeinen I, Soldermann N, Kashyap A, Uzel G, Lenardo MJ, Patel DD, Lucas CL, Burkhart C. Effective “activated PI3Kδ syndrome”–targeted therapy with the PI3Kδ inhibitor leniolisib. Blood 2017, 130: 2307-2316. PMID: 28972011, PMCID: PMC5701526, DOI: 10.1182/blood-2017-08-801191.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsChemokinesChildChild, PreschoolClass I Phosphatidylinositol 3-KinasesDemographyDose-Response Relationship, DrugFemaleHumansImmunoglobulin MImmunologic Deficiency SyndromesInfantLymph NodesLymphocyte ActivationMaleMolecular Targeted TherapyMutationOrgan SizePhenotypePrimary Immunodeficiency DiseasesProtein Kinase InhibitorsPyridinesPyrimidinesRatsSpleenT-LymphocytesTOR Serine-Threonine KinasesTransfectionConceptsImmune dysregulationT cellsB cellsElevated serum immunoglobulin MPI3K/Akt pathway activityDose-escalation studyLymph node sizeSenescent T cellsWeeks of treatmentDose-dependent suppressionTransitional B cellsTumor necrosis factorDose-dependent reductionPrecision medicine therapiesSerum immunoglobulin MNaive B cellsT cell blastsAkt pathway activityAPDS patientsPI3Kδ pathwayInflammatory markersPD-1Clinical parametersSpleen volumeImmune deficiency
2016
PI3Kδ and primary immunodeficiencies
Lucas CL, Chandra A, Nejentsev S, Condliffe AM, Okkenhaug K. PI3Kδ and primary immunodeficiencies. Nature Reviews Immunology 2016, 16: 702-714. PMID: 27616589, PMCID: PMC5291318, DOI: 10.1038/nri.2016.93.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCell DifferentiationCellular SenescenceEnzyme ActivationGene Expression RegulationHumansImmune SystemImmunityImmunologic Deficiency SyndromesLymphocyte ActivationLymphocytesMolecular Targeted TherapyMutationPhosphatidylinositol 3-KinasesPhosphoinositide-3 Kinase InhibitorsProtein SubunitsSignal TransductionConceptsPrimary immunodeficiencyT cellsHeterozygous mutationsAntibody replacement therapyStructural lung damageRegulatory T cellsT cell senescencePI3Kδ inhibitor idelalisibRecurrent sinopulmonary infectionsB-cell malignanciesHerpes family virusesMTOR inhibitor rapamycinPI3Kδ syndromeMost patientsLung damageLymphoma trialsReplacement therapyLymphoproliferative diseaseSinopulmonary infectionsAntibody responseP110δ catalytic subunitCell malignanciesB cellsImmune systemPatients
2015
Genomics of Immune Diseases and New Therapies
Lenardo M, Lo B, Lucas CL. Genomics of Immune Diseases and New Therapies. Annual Review Of Immunology 2015, 34: 1-29. PMID: 26735698, PMCID: PMC5736009, DOI: 10.1146/annurev-immunol-041015-055620.Peer-Reviewed Original ResearchConceptsDNA sequencing technologiesMagnesium transportersSequencing technologiesNew genetic diseasesGenomicsGenetic lossGenetic diseasesMolecular definitionGenetic pathogenesisPatient phenotypesBiochemical investigationsImmune regulationImmune diseasesPrecision medicine treatmentImmunological diseasesNew therapiesGenetic counselingTransportersAdditional examplesPhenotypeRegulationGreat advancesImproved diagnosis