2024
Meta-analysis identifies common gut microbiota associated with multiple sclerosis
Lin Q, Dorsett Y, Mirza A, Tremlett H, Piccio L, Longbrake E, Choileain S, Hafler D, Cox L, Weiner H, Yamamura T, Chen K, Wu Y, Zhou Y. Meta-analysis identifies common gut microbiota associated with multiple sclerosis. Genome Medicine 2024, 16: 94. PMID: 39085949, PMCID: PMC11293023, DOI: 10.1186/s13073-024-01364-x.Peer-Reviewed Original ResearchConceptsRRNA gene sequence dataGroups of microbial taxaGene sequence dataMicrobiome community structureAbundance of FaecalibacteriumAbundance of PrevotellaAbundance of ActinomycesSequence dataBeta diversityMicrobial taxaGut microbiotaMicrobial compositionCommunity structureNetwork analysisGutBacterial correlationsMicrobiotaAbundanceMultiple sclerosisDiverse groupMeta-analysisDiversityTaxaFaecalibacteriumConclusionsOur meta-analysisEmerging Cerebrospinal Fluid Biomarkers of Disease Activity and Progression in Multiple Sclerosis
Cross A, Gelfand J, Thebault S, Bennett J, von Büdingen H, Cameron B, Carruthers R, Edwards K, Fallis R, Gerstein R, Giacomini P, Greenberg B, Hafler D, Ionete C, Kaunzner U, Kodama L, Lock C, Longbrake E, Musch B, Pardo G, Piehl F, Weber M, Yuen S, Ziemssen T, Bose G, Freedman M, Anania V, Ramesh A, Winger R, Jia X, Herman A, Harp C, Bar-Or A. Emerging Cerebrospinal Fluid Biomarkers of Disease Activity and Progression in Multiple Sclerosis. JAMA Neurology 2024, 81: 373-383. PMID: 38466277, PMCID: PMC10928543, DOI: 10.1001/jamaneurol.2024.0017.Peer-Reviewed Original ResearchPrimary progressive MSGlial fibrillary acidic proteinNeurofilament heavy chainRelapsing MSCerebrospinal fluidTest cohortMultiple sclerosisDisease-modifying MS therapyMulticenter study of patientsBiomarkers of disease activityAnti-CD20 treatmentCentral nervous system biologyClinical follow-upConfirmation cohortT2 lesion volumeStudy of patientsHeavy chainCSF-GFAP levelsMS disease progressionMagnetic resonance imaging measuresNeurofilament light chainActivated glial markersStudy assessed dataFibrillary acidic proteinAnti-CD20
2023
Microfluidic Immuno‐Serolomic Assay Reveals Systems Level Association with COVID‐19 Pathology and Vaccine Protection (Small Methods 10/2023)
Kim D, Biancon G, Bai Z, VanOudenhove J, Liu Y, Kothari S, Gowda L, Kwan J, Buitrago‐Pocasangre N, Lele N, Asashima H, Racke M, Wilson J, Givens T, Tomayko M, Schulz W, Longbrake E, Hafler D, Halene S, Fan R. Microfluidic Immuno‐Serolomic Assay Reveals Systems Level Association with COVID‐19 Pathology and Vaccine Protection (Small Methods 10/2023). Small Methods 2023, 7 DOI: 10.1002/smtd.202370057.Peer-Reviewed Original ResearchPrior 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 strategiesMicrofluidic Immuno‐Serolomic Assay Reveals Systems Level Association with COVID‐19 Pathology and Vaccine Protection
Kim D, Biancon G, Bai Z, VanOudenhove J, Liu Y, Kothari S, Gowda L, Kwan J, Buitrago‐Pocasangre N, Lele N, Asashima H, Racke M, Wilson J, Givens T, Tomayko M, Schulz W, Longbrake E, Hafler D, Halene S, Fan R. Microfluidic Immuno‐Serolomic Assay Reveals Systems Level Association with COVID‐19 Pathology and Vaccine Protection. Small Methods 2023, 7: e2300594. PMID: 37312418, PMCID: PMC10592458, DOI: 10.1002/smtd.202300594.Peer-Reviewed Original ResearchConceptsB cell depletion therapyAcute COVID infectionAnti-spike IgGHigh-risk patientsCoronavirus disease-19COVID-19 pathologyDepletion therapyVaccine protectionAntibody responseCOVID infectionHematologic malignanciesImmune protectionDisease-19Healthy donorsMultiple time pointsSerology assaysBlood samplesSoluble markersB cellsImmunization strategiesPatientsFunctional deficiencySerological analysisTime pointsClonotype diversityDifferential 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 cascade
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 MRIThe CELLO trial: Protocol of a planned phase 4 study to assess the efficacy of Ocrelizumab in patients with radiologically isolated syndrome
Longbrake EE, Hua LH, Mowry EM, Gauthier SA, Alvarez E, Cross AH, Pei J, Priest J, Raposo C, Hafler DA, Winger RC. The CELLO trial: Protocol of a planned phase 4 study to assess the efficacy of Ocrelizumab in patients with radiologically isolated syndrome. Multiple Sclerosis And Related Disorders 2022, 68: 104143. PMID: 36031693, PMCID: PMC9772048, DOI: 10.1016/j.msard.2022.104143.Peer-Reviewed Original ResearchConceptsEfficacy of ocrelizumabMultiple sclerosisImmunologic biomarkersClinical trialsTransient B-cell depletionClinical multiple sclerosisCSF immune cellsEffects of ocrelizumabMS disease pathophysiologyNew brain lesionsOvert neurological symptomsB-cell depletionPlacebo-controlled studyPhase 4 studyLong-term outcomesPatient-reported outcomesPrimary progressive MSHumanized monoclonal antibodyFirst-degree relativesB cell biologySubtle cognitive impairmentEligible patientsImmune recoveryProgressive MSWeek 48Cerebrospinal Fluid Lymphocytic Pleocytosis is Associated With Enhanced Blood-Brain Barrier Breakdown at the Time of Multiple Sclerosis Diagnosis (P15-4.007)
Sivakolundu D, Kopyto M, Hill K, Elhusseiny H, Fulbright R, Hafler D, Longbrake E. Cerebrospinal Fluid Lymphocytic Pleocytosis is Associated With Enhanced Blood-Brain Barrier Breakdown at the Time of Multiple Sclerosis Diagnosis (P15-4.007). Neurology 2022, 98 DOI: 10.1212/wnl.98.18_supplement.2811.Peer-Reviewed Original Research
2021
23Na imaging: Worth its salt for understanding multiple sclerosis
Longbrake EE, Hafler DA. 23Na imaging: Worth its salt for understanding multiple sclerosis. Proceedings Of The National Academy Of Sciences Of The United States Of America 2021, 118: e2110799118. PMID: 34376559, PMCID: PMC8379906, DOI: 10.1073/pnas.2110799118.Commentaries, Editorials and Letters
2020
B 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 onsetSiponimod Chips Away at Progressive MS
Longbrake EE, Hafler DA. Siponimod Chips Away at Progressive MS. Cell 2019, 179: 1440. PMID: 31951523, PMCID: PMC8023412, DOI: 10.1016/j.cell.2019.11.034.Peer-Reviewed Original ResearchConceptsProgressive multiple sclerosisGadolinium-enhancing MRI lesionsInflammatory disease activityImmunomodulatory medicationsDisability progressionDisease activityMRI lesionsProgressive MSNeurologic disabilityPMS patientsMultiple sclerosisSiponimodMedicationsSclerosisPatientsLesionsBedsideProgressionCHAPTER 2 Genetics of Multiple Sclerosis
Abulaban A, Hafler D, Longbrake E. CHAPTER 2 Genetics of Multiple Sclerosis. 2019, 33-54. DOI: 10.1039/9781788016070-00033.ChaptersMultiple sclerosisCentral nervous systemImmune cell infiltratesComplex autoimmune diseaseEnvironmental risk factorsExtensive CNS demyelinationMS therapyAxonal damageCell infiltrateCNS demyelinationAutoimmune diseasesRisk factorsGenetic predispositionNervous systemDisease severityDiseaseSclerosisComplex genetic diseasesChapter 2 GeneticsGenetic diseasesDemyelinationInfiltratesAutoimmunityPathogenesisTherapy
2016
Linking Genotype to Clinical Phenotype in Multiple Sclerosis: In Search of the Holy Grail
Longbrake EE, Hafler DA. Linking Genotype to Clinical Phenotype in Multiple Sclerosis: In Search of the Holy Grail. JAMA Neurology 2016, 73: 777-8. PMID: 27244583, PMCID: PMC5198230, DOI: 10.1001/jamaneurol.2016.1227.Peer-Reviewed Original Research