Featured Publications
Differential effects of anti-CD20 therapy on CD4 and CD8 T cells and implication of CD20-expressing CD8 T cells in MS disease activity
Shinoda K, Li R, Rezk A, Mexhitaj I, Patterson K, Kakara M, Zuroff L, Bennett J, von Büdingen H, Carruthers R, Edwards K, Fallis R, Giacomini P, Greenberg B, Hafler D, Ionete C, Kaunzner U, Lock C, Longbrake E, Pardo G, Piehl F, Weber M, Ziemssen T, Jacobs D, Gelfand J, Cross A, Cameron B, Musch B, Winger R, Jia X, Harp C, Herman A, Bar-Or A. Differential effects of anti-CD20 therapy on CD4 and CD8 T cells and implication of CD20-expressing CD8 T cells in MS disease activity. Proceedings Of The National Academy Of Sciences Of The United States Of America 2023, 120: e2207291120. PMID: 36634138, PMCID: PMC9934304, DOI: 10.1073/pnas.2207291120.Peer-Reviewed Original ResearchConceptsEarly disease activityDisease activityCD8 T cellsT cellsCD20 therapyPeripheral blood mononuclear cellsCellular immune profilesNew disease activityMS disease activityT cell poolMultiple sclerosis patientsAnti-inflammatory profileBlood mononuclear cellsTreatment-associated changesMultiparametric flow cytometryCentral nervous systemFurther dosingRepeat infusionsImmune profileMS patientsSclerosis patientsValidation cohortMononuclear cellsRelapse developmentImmune cascadePrior cycles of anti-CD20 antibodies affect antibody responses after repeated SARS-CoV-2 mRNA vaccination
Asashima H, Kim D, Wang K, Lele N, Buitrago-Pocasangre N, Lutz R, Cruz I, Raddassi K, Ruff W, Racke M, Wilson J, Givens T, Grifoni A, Weiskopf D, Sette A, Kleinstein S, Montgomery R, Shaw A, Li F, Fan R, Hafler D, Tomayko M, Longbrake E. Prior cycles of anti-CD20 antibodies affect antibody responses after repeated SARS-CoV-2 mRNA vaccination. JCI Insight 2023, 8: e168102. PMID: 37606046, PMCID: PMC10543713, DOI: 10.1172/jci.insight.168102.Peer-Reviewed Original ResearchConceptsSARS-CoV-2 mRNA vaccinationB-cell-depleted patientsB-cell depletionAntibody responseMRNA vaccinationThird doseCell depletionT cellsClaude D. Pepper Older Americans Independence CenterB cellsNational Multiple Sclerosis SocietyAnti-CD20 antibodySpike-specific antibodiesMultiple Sclerosis SocietyLow cumulative exposureLogistic regression modelsImportant clinical needCD20 therapyCD20 treatmentMost patientsThird vaccineSerologic responseVaccine dosesMRNA vaccinesVaccination strategies
2022
Impaired TIGIT expression on B cells drives circulating follicular helper T cell expansion in multiple sclerosis
Asashima H, Axisa PP, Pham THG, Longbrake EE, Ruff WE, Lele N, Cohen I, Raddassi K, Sumida TS, Hafler DA. Impaired TIGIT expression on B cells drives circulating follicular helper T cell expansion in multiple sclerosis. Journal Of Clinical Investigation 2022, 132: e156254. PMID: 36250467, PMCID: PMC9566906, DOI: 10.1172/jci156254.Peer-Reviewed Original ResearchConceptsRelapsing-remitting multiple sclerosisMemory B cellsCTfh cellsB cellsTIGIT expressionMultiple sclerosisT cellsFollicular helper T cellsHealthy age-matched controlsB-cell depletionT cell expansionHelper T cellsAge-matched controlsB cell functionB-cell pathwayDifferential gene expression signaturesTfh cellsDisease activityGene expression signaturesCell depletionCD40 ligandTranscription factor TCF4Disease pathogenesisImmune systemNew MRI
2020
Dimethyl fumarate treatment shifts the immune environment toward an anti-inflammatory cell profile while maintaining protective humoral immunity
Longbrake EE, Mao-Draayer Y, Cascione M, Zielinski T, Bame E, Brassat D, Chen C, Kapadia S, Mendoza JP, Miller C, Parks B, Xing D, Robertson D. Dimethyl fumarate treatment shifts the immune environment toward an anti-inflammatory cell profile while maintaining protective humoral immunity. Multiple Sclerosis Journal 2020, 27: 883-894. PMID: 32716690, PMCID: PMC8023410, DOI: 10.1177/1352458520937282.Peer-Reviewed Original ResearchConceptsDelayed-release dimethyl fumarateAbsolute lymphocyte countT cellsMedian absolute lymphocyte countEffector memory T cellsDimethyl fumarate treatmentPhase 3b studyTotal T cellsAdverse event ratesMemory T cellsProtective humoral immunityForms of MSDMF BIDLymphocyte subsetsAdverse eventsLymphocyte countTotal IgAImmune environmentImmunoglobulin levelsNaive CD4Sustained efficacyHumoral immunityFumarate treatmentSubclass levelsCount changesB Cells, T Cells and Inflammatory CSF Biomarkers in Primary Progressive MS and Relapsing MS in the OBOE (Ocrelizumab Biomarker Outcome Evaluation) Trial (1635)
Bar-Or A, Bennett J, Von Budingen H, Carruthers R, Edwards K, Fallis R, Fiore D, Gelfand J, Giacomini P, Greenberg B, Hafler D, Longbrake E, Assman B, Ionete C, Kaunzner U, Lock C, Ma X, Musch B, Pardo G, Pei J, Piehl F, Weber M, Ziemssen T, Herman A, Harp C, Cross A. B Cells, T Cells and Inflammatory CSF Biomarkers in Primary Progressive MS and Relapsing MS in the OBOE (Ocrelizumab Biomarker Outcome Evaluation) Trial (1635). Neurology 2020, 94 DOI: 10.1212/wnl.94.15_supplement.1635.Peer-Reviewed Original Research
2019
CXCR3+ T cells in multiple sclerosis correlate with reduced diversity of the gut microbiome
Choileáin SN, Kleinewietfeld M, Raddassi K, Hafler DA, Ruff WE, Longbrake EE. CXCR3+ T cells in multiple sclerosis correlate with reduced diversity of the gut microbiome. Journal Of Translational Autoimmunity 2019, 3: 100032. PMID: 32743517, PMCID: PMC7388357, DOI: 10.1016/j.jtauto.2019.100032.Peer-Reviewed Original ResearchInflammatory T cell subsetsCentral nervous systemT cell subsetsMultiple sclerosisT cellsGut microbiomeCell subsetsCNS-reactive T cellsRelapsing-remitting MS patientsGrey matter inflammationGut-immune axisExpression of CXCR3CD8 T cellsAltered gut microbiomeAutoreactive T cellsMultiple sclerosis correlateGut microbiome compositionInflammatory subsetMS pathogenesisMS patientsTh1 phenotypeAxonal degenerationAutoimmune diseasesCascade of eventsDisease onset
2017
Dimethyl fumarate induces changes in B- and T-lymphocyte function independent of the effects on absolute lymphocyte count
Longbrake EE, Cantoni C, Chahin S, Cignarella F, Cross AH, Piccio L. Dimethyl fumarate induces changes in B- and T-lymphocyte function independent of the effects on absolute lymphocyte count. Multiple Sclerosis Journal 2017, 24: 728-738. PMID: 28480794, PMCID: PMC5665729, DOI: 10.1177/1352458517707069.Peer-Reviewed Original ResearchConceptsAbsolute lymphocyte countDMF-treated patientsPeripheral blood mononuclear cellsDimethyl fumarateLymphocyte countPeptide stimulationLow absolute lymphocyte countFollicular T helper cellsDMF-induced lymphopeniaInvariant T (MAIT) cellsPro-inflammatory cytokinesT-cell phenotypeBlood mononuclear cellsT cell productionT helper cellsT lymphocyte functionMemory B cellsActivation-induced cell deathMultiparametric flow cytometryUntreated patientsMultiple sclerosisMononuclear cellsHealthy controlsT cellsT lymphocytes
2015
Dimethyl fumarate selectively reduces memory T cells in multiple sclerosis patients
Longbrake E, Ramsbottom M, Cantoni C, Ghezzi L, Cross A, Piccio L. Dimethyl fumarate selectively reduces memory T cells in multiple sclerosis patients. Multiple Sclerosis Journal 2015, 22: 1061-1070. PMID: 26459150, PMCID: PMC4829494, DOI: 10.1177/1352458515608961.Peer-Reviewed Original ResearchConceptsDMF-treated patientsMemory T cellsMultiple sclerosis patientsT cellsMS patientsDendritic cellsSclerosis patientsEffector memory T cellsUntreated MS patientsMyeloid dendritic cellsAbsolute lymphocyte countPlasmacytoid dendritic cellsNatural killer cellsNaïve T cellsMechanism of actionLymphocyte countLymphopenic patientsRegulatory cellsKiller cellsPeripheral bloodImmune cellsHealthy controlsPatientsB cellsFlow cytometry