2025
Alterations in Gut Microbiome-Host Relationships After Immune Perturbation in Patients With Multiple Sclerosis
Gupta V, Janda G, Pump H, Lele N, Cruz I, Cohen I, Ruff W, Hafler D, Sung J, Longbrake E. Alterations in Gut Microbiome-Host Relationships After Immune Perturbation in Patients With Multiple Sclerosis. Neurology Neuroimmunology & Neuroinflammation 2025, 12: e200355. PMID: 39819054, PMCID: PMC11741292, DOI: 10.1212/nxi.0000000000200355.Peer-Reviewed Original ResearchConceptsAmplicon sequence variantsIgA-coatedGut microbiomeBacterial fractionRRNA gene amplicon sequencingLong-read sequencingGut microbial symbiontsGene amplicon sequencingMultiple sclerosisStool samplesProportion of bacteriaB cellsHost-microbial interfaceAnti-CD20 monoclonal antibody treatmentDiagnosing MSMicrobial symbiontsIgA-secreting B cellsTaxonomic resolutionSequence variantsAmplicon sequencingB-cell depletionFecal microbiotaMonths of treatmentMonoclonal antibody treatmentDevelopment of autoimmunity
2023
Prior 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 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 48