2018
Low-Frequency and Rare-Coding Variation Contributes to Multiple Sclerosis Risk
Consortium I, Mitrovič M, Patsopoulos N, Beecham A, Dankowski T, Goris A, Dubois B, D’hooghe M, Lemmens R, Van Damme P, Søndergaard H, Sellebjerg F, Sorensen P, Ullum H, Thørner L, Werge T, Saarela J, Cournu-Rebeix I, Damotte V, Fontaine B, Guillot-Noel L, Lathrop M, Vukusik S, Gourraud P, Andlauer T, Pongratz V, Buck D, Gasperi C, Bayas A, Heesen C, Kümpfel T, Linker R, Paul F, Stangel M, Tackenberg B, Bergh F, Warnke C, Wiendl H, Wildemann B, Zettl U, Ziemann U, Tumani H, Gold R, Grummel V, Hemmer B, Knier B, Lill C, Luessi F, Dardiotis E, Agliardi C, Barizzone N, Mascia E, Bernardinelli L, Comi G, Cusi D, Esposito F, Ferrè L, Comi C, Galimberti D, Leone M, Sorosina M, Mescheriakova J, Hintzen R, van Duijn C, Theunissen C, Bos S, Myhr K, Celius E, Lie B, Spurkland A, Comabella M, Montalban X, Alfredsson L, Stridh P, Hillert J, Jagodic M, Piehl F, Jelčić I, Martin R, Sospedra M, Ban M, Hawkins C, Hysi P, Kalra S, Karpe F, Khadake J, Lachance G, Neville M, Santaniello A, Caillier S, Calabresi P, Cree B, Cross A, Davis M, Haines J, de Bakker P, Delgado S, Dembele M, Edwards K, Fitzgerald K, Hakonarson H, Konidari I, Lathi E, Manrique C, Pericak-Vance M, Piccio L, Schaefer C, McCabe C, Weiner H, Goldstein J, Olsson T, Hadjigeorgiou G, Taylor B, Tajouri L, Charlesworth J, Booth D, Harbo H, Ivinson A, Hauser S, Compston A, Stewart G, Zipp F, Barcellos L, Baranzini S, Martinelli-Boneschi F, D’Alfonso S, Ziegler A, Oturai A, McCauley J, Sawcer S, Oksenberg J, De Jager P, Kockum I, Hafler D, Cotsapas C. Low-Frequency and Rare-Coding Variation Contributes to Multiple Sclerosis Risk. Cell 2018, 175: 1679-1687.e7. PMID: 30343897, PMCID: PMC6269166, DOI: 10.1016/j.cell.2018.09.049.Peer-Reviewed Original ResearchConceptsRare coding variationsGenome-wide association studiesNon-coding variationCommon variant signalsSubstantial linkage disequilibriumLow-frequency variantsNovel genesCell homeostasisAssociation studiesComplex neurological diseasesLinkage disequilibriumGenetic variantsCommon variantsHeritabilityRich resourceGenesVariantsKey pathogenic roleIndividual familiesEpistasisAdditive effectBiologyHomeostasisMutationsNeurological diseases
2017
Resisting fatal attraction: a glioma oncometabolite prevents CD8+ T cell recruitment
Lucca LE, Hafler DA. Resisting fatal attraction: a glioma oncometabolite prevents CD8+ T cell recruitment. Journal Of Clinical Investigation 2017, 127: 1218-1220. PMID: 28319049, PMCID: PMC5373854, DOI: 10.1172/jci93565.Peer-Reviewed Original ResearchConceptsT cellsRecruitment of CD8Antitumor immune responseT cell recruitmentMigration of CD8Cell lung tumorsSyngeneic gliomaChemokines CXCL9Tumor escapeTumor controlImmune infiltrationMetastatic melanomaClinical trialsMalignant gliomasExpression of STAT1Immune surveillanceLung tumorsImmune responseAggressive cancerCell recruitmentCD8Tumor destructionTumorsGliomasCommon mutations
2016
NR1H3 p.Arg415Gln Is Not Associated to Multiple Sclerosis Risk
Consortium T, Antel J, Ban M, Baranzini S, Barcellos L, Barizzone N, Beecham A, Berge T, Bernardinelli L, Booth D, Bos S, Buck D, Butkiewicz M, Celius E, Comabella M, Compston A, Dedham K, Cotsapas C, Alfonso S, De Jager P, Dubois B, Duquette P, Fontaine B, Gasperi C, Gil E, Goris A, Gourraud P, Graetz C, Gyllenberg A, Hadjigeorgiou G, Hafler D, Hribko D, Haines J, Harbo H, Hauser S, Warto S, Hawkins C, Hemmer B, Henry R, Hintzen R, Horakova D, Ivinson A, Howard M, Jelcic I, Kaskow B, Kira J, Kleinova P, Kockum I, Kucerova K, Lill C, Luessi F, Malhotra S, Martin R, Martinelli F, Matsushita T, McCabe C, McCauley J, Mescheriakkova J, Mitrovic M, Moen S, Montalban X, Muhlau M, Nakmura Y, Oksenberg J, Olsson T, Oturai A, Palotie A, Patsopoulos N, Pavlicova J, Pericak-Vance P, Piehl F, Rebeix I, Rioux J, Saarela J, Sawcer S, Sellebjerg F, Sondergaard H, Sorensen P, Sospedra M, Spurkland A, Stewart G, Taylor B, Uitterlinden A, Van Duijn C, Zipp F. NR1H3 p.Arg415Gln Is Not Associated to Multiple Sclerosis Risk. Neuron 2016, 92: 333-335. PMID: 27764667, PMCID: PMC5641967, DOI: 10.1016/j.neuron.2016.09.052.Peer-Reviewed Original ResearchConceptsPrimary progressive diseaseMultiple sclerosis riskProgressive diseaseMultiple sclerosisPatient's likelihoodDisease subtypesPatient collectionInsufficient sample sizeCommon variant associationsLow-frequency associationMendelian formsAssociationRecent studiesCertain individualsSample sizeVariant associationsSclerosisSubtypesDiseaseNeurons
2013
Clinical relevance and functional consequences of the TNFRSF1A multiple sclerosis locus
Ottoboni L, Frohlich IY, Lee M, Healy BC, Keenan BT, Xia Z, Chitnis T, Guttmann CR, Khoury SJ, Weiner HL, Hafler DA, De Jager PL. Clinical relevance and functional consequences of the TNFRSF1A multiple sclerosis locus. Neurology 2013, 81: 1891-1899. PMID: 24174586, PMCID: PMC3843384, DOI: 10.1212/01.wnl.0000436612.66328.8a.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsArginineChemokine CXCL10FemaleGene Expression RegulationGenetic Predisposition to DiseaseGenotypeGlutamineHEK293 CellsHumansImmunologic FactorsLongitudinal StudiesMaleMonocytesMultiple SclerosisMutationPhorbol EstersReceptors, Tumor Necrosis Factor, Type IRNA IsoformsSignal TransductionTumor Necrosis Factor-alphaConceptsTNFRSF1A locusSusceptibility allelesFunctional consequencesRobust transcriptional responseTranscriptional responseCytoplasmic domainRNA isoformsTNF-α stimulationRho GTPaseMS susceptibility genesMS geneG proteinsSusceptibility genesMolecular levelTNF pathwayGenesAltered expressionLociTNF-α pathwayAllelesRisk allelesPathwayGTPaseImmune functionTransmembrane
2011
An Innate Role for IL-17
Dominguez-Villar M, Hafler DA. An Innate Role for IL-17. Science 2011, 332: 47-48. PMID: 21454778, DOI: 10.1126/science.1205311.Peer-Reviewed Original ResearchConceptsImmune responseImmune dysregulation polyendocrinopathyAbnormal immune responseRegulatory immune cellsRegulatory T cellsHuman autoimmune disordersCytokine interleukin-17Normal immune responseTranscription factor Foxp3IL-17Interleukin-17Autoimmune disordersAutoimmune diseasesImmune cellsImmune system processFOXP3 geneFactor Foxp3T cellsImmune systemFungal infectionsGenetic mutationsHuman genetic mutationsCytokinesInfectionCell types
2007
Risk Alleles for Multiple Sclerosis Identified by a Genomewide Study
Hafler D, Compston A, Sawcer S, Lander E, Daly M, De Jager P, de Bakker P, Gabriel S, Mirel D, Ivinson A, Pericak-Vance M, Gregory S, Rioux J, McCauley J, Haines J, Barcellos L, Cree B, Oksenberg J, Hauser S. Risk Alleles for Multiple Sclerosis Identified by a Genomewide Study. New England Journal Of Medicine 2007, 357: 851-862. PMID: 17660530, DOI: 10.1056/nejmoa073493.Peer-Reviewed Original ResearchMeSH KeywordsAdolescentAdultAgedAllelesFemaleGenetic Predisposition to DiseaseGenome, HumanHLA-DR alpha-ChainsHLA-DR AntigensHumansInterleukin-2 Receptor alpha SubunitInterleukin-7 Receptor alpha SubunitLinkage DisequilibriumMaleMiddle AgedMultiple SclerosisMutationOligonucleotide Array Sequence AnalysisPolymorphism, Single NucleotideRisk FactorsConceptsMultiple sclerosisReceptor alpha geneSingle nucleotide polymorphismsControl subjectsCase subjectsInterleukin-7 receptor alpha geneHeritable risk factorsAlpha geneRisk factorsFamily triosSclerosisRisk allelesHLA lociHLA-DRA locusTransmission disequilibrium testStringent P valueP-valueEffect sizeSignificant heritable componentInterleukin-2 receptor alpha geneNonsynonymous single nucleotide polymorphismsGenomewide association studiesMultiple single nucleotide polymorphismsSubjectsAssociationA Local Antigen-Driven Humoral Response Is Present in the Inflammatory Myopathies
Bradshaw EM, Orihuela A, McArdel SL, Salajegheh M, Amato AA, Hafler DA, Greenberg SA, O’Connor K. A Local Antigen-Driven Humoral Response Is Present in the Inflammatory Myopathies. The Journal Of Immunology 2007, 178: 547-556. PMID: 17182595, DOI: 10.4049/jimmunol.178.1.547.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAmino Acid SequenceAntibody FormationAutoantigensB-Lymphocyte SubsetsFemaleGenes, Immunoglobulin Heavy ChainHumansImmunoglobulin Switch RegionImmunoglobulin Variable RegionMaleMicrodissectionMiddle AgedMolecular Sequence DataMutationMyocardiumMyositisReceptors, Antigen, B-CellSyndecan-1Transcription, GeneticConceptsInclusion body myositisLaser capture microdissectionBody myositisCapture microdissectionInflammatory myopathiesMuscle tissueInsertions/deletionsT cell-mediated diseaseGene sequencesCell-mediated diseaseGene transcriptsInflamed muscle tissueAg-specific responsesAg receptorB cell maturationPlasma cell populationPutative autoimmune disordersControl muscle tissueSignificant somatic mutationsIndividual cellsVariable region gene sequencesOligoclonal expansionInflammatory infiltrateSomatic mutationsMuscle weakness