2021
Sex-Biased Aging Effects on Ig Somatic Hypermutation Targeting
Cui A, Chawla DG, Kleinstein SH. Sex-Biased Aging Effects on Ig Somatic Hypermutation Targeting. The Journal Of Immunology 2021, 206: 101-108. PMID: 33288546, PMCID: PMC8582005, DOI: 10.4049/jimmunol.2000576.Peer-Reviewed Original ResearchConceptsOlder individualsDNA mismatch repair genesSex groupsObserved clinical differencesMismatch repair genesB cell IgDecreased expression levelDNA repair activityImmunologic responseClinical differencesAb responsesFemale human subjectsOld maleAged individualsImpaired levelDifferent agesYounger counterpartsPhase ILargest fold changeYoung individualsError-prone DNA repair activityExpression levelsHuman subjectsMutation patternsRepair activity
2016
Autoreactive T Cells from Patients with Myasthenia Gravis Are Characterized by Elevated IL-17, IFN-γ, and GM-CSF and Diminished IL-10 Production
Cao Y, Amezquita RA, Kleinstein SH, Stathopoulos P, Nowak RJ, O'Connor KC. Autoreactive T Cells from Patients with Myasthenia Gravis Are Characterized by Elevated IL-17, IFN-γ, and GM-CSF and Diminished IL-10 Production. The Journal Of Immunology 2016, 196: 2075-2084. PMID: 26826242, PMCID: PMC4761502, DOI: 10.4049/jimmunol.1501339.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAged, 80 and overAutoimmunityCD4-Positive T-LymphocytesCell SeparationCytokinesEnzyme-Linked Immunosorbent AssayFemaleGranulocyte-Macrophage Colony-Stimulating FactorHumansInterferon-gammaInterleukin-10Interleukin-17MaleMiddle AgedMyasthenia GravisPhenotypePolymerase Chain ReactionT-Lymphocyte SubsetsConceptsAutoreactive T cellsT cell compartmentHealthy control subjectsMyasthenia gravisT cellsMG patientsIL-17Control subjectsT cell librariesB cellsGM-CSFMemory T cell compartmentElevated IL-17Prototypical autoimmune diseaseIL-10 productionMemory T cellsCell compartmentIL-10 expressionB cell compartmentPathogenic phenotypeMG cohortPathogenic autoantibodiesAutoimmune responseClinical manifestationsProinflammatory phenotype
2015
Aging-dependent alterations in gene expression and a mitochondrial signature of responsiveness to human influenza vaccination
Thakar J, Mohanty S, West AP, Joshi SR, Ueda I, Wilson J, Meng H, Blevins TP, Tsang S, Trentalange M, Siconolfi B, Park K, Gill TM, Belshe RB, Kaech SM, Shadel GS, Kleinstein SH, Shaw AC. Aging-dependent alterations in gene expression and a mitochondrial signature of responsiveness to human influenza vaccination. Aging 2015, 7: 38-51. PMID: 25596819, PMCID: PMC4356402, DOI: 10.18632/aging.100720.Peer-Reviewed Original ResearchMeSH KeywordsAdultAge FactorsAgedAged, 80 and overAgingCells, CulturedDNA, MitochondrialFemaleGene Expression ProfilingGene Expression RegulationGenome-Wide Association StudyHumansInfluenza VaccinesInfluenza, HumanLeukocytes, MononuclearMaleMitochondriaMitochondrial TurnoverOligonucleotide Array Sequence AnalysisOxidative PhosphorylationSeasonsTime FactorsTreatment OutcomeVaccinationYoung AdultConceptsPlasma cell signatureDay 2Influenza vaccinationDay 7Cell signatureOlder adultsInfluenza vaccine responsesAdults meeting criteriaType I interferon responseAge-associated impairmentAge-dependent alterationsI interferon responseMitochondrial biogenesisResponse signatureVaccine seasonVaccine respondersFrail subjectsInfluenza vaccineVaccine responsesVaccine responsivenessGene expression microarray analysisAbsent responseYounger respondersDay 28Meeting criteria
2014
Systems Immunology Reveals Markers of Susceptibility to West Nile Virus Infection
Qian F, Goel G, Meng H, Wang X, You F, Devine L, Raddassi K, Garcia MN, Murray KO, Bolen CR, Gaujoux R, Shen-Orr SS, Hafler D, Fikrig E, Xavier R, Kleinstein SH, Montgomery RR. Systems Immunology Reveals Markers of Susceptibility to West Nile Virus Infection. MSphere 2014, 22: 6-16. PMID: 25355795, PMCID: PMC4278927, DOI: 10.1128/cvi.00508-14.Peer-Reviewed Original ResearchConceptsWest Nile virus infectionVirus infectionMyeloid dendritic cellsMarker of susceptibilityPotential therapeutic strategySeverity of infectionSevere neurological diseaseOlder patientsAcute infectionDendritic cellsCXCL10 expressionDetectable yearsImmunity-related genesStratified cohortWNV infectionTherapeutic strategiesPathogenic mechanismsAnimal studiesNeurological diseasesDisease severityVivo infectionPredictive signatureInfectionProminent alterationsPrimary cellsB cells populating the multiple sclerosis brain mature in the draining cervical lymph nodes
Stern JN, Yaari G, Vander Heiden JA, Church G, Donahue WF, Hintzen RQ, Huttner AJ, Laman JD, Nagra RM, Nylander A, Pitt D, Ramanan S, Siddiqui BA, Vigneault F, Kleinstein SH, Hafler DA, O'Connor KC. B cells populating the multiple sclerosis brain mature in the draining cervical lymph nodes. Science Translational Medicine 2014, 6: 248ra107. PMID: 25100741, PMCID: PMC4388137, DOI: 10.1126/scitranslmed.3008879.Peer-Reviewed Original ResearchConceptsCervical lymph nodesCentral nervous systemB cellsCerebrospinal fluidLymph nodesMultiple sclerosisLymphoid tissueCNS of patientsCNS B cellsAntigen-experienced B cellsMultiple sclerosis brainSecondary lymphoid tissuesB cell compartmentB cell trafficB cell maturationImmunomodulatory therapyImmune infiltratesPeripheral bloodInflammatory diseasesLymphocyte transmigrationPeripheral tissuesNervous systemMembers of clonesCell maturationCell trafficImmune Markers Associated with Host Susceptibility to Infection with West Nile Virus
Qian F, Thakar J, Yuan X, Nolan M, Murray KO, Lee WT, Wong SJ, Meng H, Fikrig E, Kleinstein SH, Montgomery RR. Immune Markers Associated with Host Susceptibility to Infection with West Nile Virus. Viral Immunology 2014, 27: 39-47. PMID: 24605787, PMCID: PMC3949440, DOI: 10.1089/vim.2013.0074.Peer-Reviewed Original ResearchConceptsWest Nile virusSevere infectionsImmune markersIL-4IL-4 levelsSerum cytokine levelsSerum IL-4Nile virusSignificant risk factorsImmune system statusPeripheral blood cellsSevere neurological diseaseCytokine levelsAntibody levelsImmune statusRisk factorsHealthy subjectsStratified cohortWNV infectionNeurological diseasesInfectionAltered expression levelsBlood cellsAltered gene expression patternsHost susceptibility