2021
Transcriptomics of bronchoalveolar lavage cells identifies new molecular endotypes of sarcoidosis
Vukmirovic M, Yan X, Gibson KF, Gulati M, Schupp JC, DeIuliis G, Adams TS, Hu B, Mihaljinec A, Woolard TN, Lynn H, Emeagwali N, Herzog EL, Chen ES, Morris A, Leader JK, Zhang Y, Garcia JGN, Maier LA, Collman RG, Drake WP, Becich MJ, Hochheiser H, Wisniewski SR, Benos PV, Moller DR, Prasse A, Koth LL, Kaminski N. Transcriptomics of bronchoalveolar lavage cells identifies new molecular endotypes of sarcoidosis. European Respiratory Journal 2021, 58: 2002950. PMID: 34083402, PMCID: PMC9759791, DOI: 10.1183/13993003.02950-2020.Peer-Reviewed Original ResearchMeSH KeywordsBronchoalveolar LavageBronchoalveolar Lavage FluidHumansSarcoidosisSarcoidosis, PulmonaryTranscriptomeConceptsWeighted gene co-expression network analysisGene co-expression network analysisCo-expression network analysisGene expression programsGene expression patternsDistinct transcriptional programsImmune response pathwaysIon Torrent ProtonMicroarray expression datasetsExpression programsTranscriptional programsPhenotypic traitsGene modulesResponse pathwaysRNA sequencingMolecular endotypesExpression patternsGene expressionHilar lymphadenopathyOrgan involvementGenomic researchMechanistic targetExpression datasetsT helper type 1T cell immune responsesElevated IL-15 concentrations in the sarcoidosis lung are independent of granuloma burden and disease phenotypes
Minasyan M, Sharma L, Pivarnik T, Liu W, Adams T, Bermejo S, Peng X, Liu A, Ishikawa G, Perry C, Kaminski N, Gulati M, Herzog EL, Dela Cruz CS, Ryu C. Elevated IL-15 concentrations in the sarcoidosis lung are independent of granuloma burden and disease phenotypes. American Journal Of Physiology - Lung Cellular And Molecular Physiology 2021, 320: l1137-l1146. PMID: 33851886, PMCID: PMC8285626, DOI: 10.1152/ajplung.00575.2020.Peer-Reviewed Original ResearchConceptsIL-15 concentrationsIL-15Bronchoalveolar lavageDisease pathogenesisSarcoidosis lungClinical manifestationsLineages of miceIL-15 receptor αHuman cohortsInflammation of sarcoidosisIL-15 levelsOngoing inflammatory processSystemic granulomatous diseaseNumber of granulomasDisease phenotypeSarcoidosis cohortTDM administrationGranuloma numberComorbid conditionsClinical progressionInterleukin-15Granulomatous diseaseInflammatory processGranuloma formationHealthy controls
2018
PD-1 up-regulation on CD4+ T cells promotes pulmonary fibrosis through STAT3-mediated IL-17A and TGF-β1 production
Celada LJ, Kropski JA, Herazo-Maya JD, Luo W, Creecy A, Abad AT, Chioma OS, Lee G, Hassell NE, Shaginurova GI, Wang Y, Johnson JE, Kerrigan A, Mason WR, Baughman RP, Ayers GD, Bernard GR, Culver DA, Montgomery CG, Maher TM, Molyneaux PL, Noth I, Mutsaers SE, Prele CM, Peebles R, Newcomb DC, Kaminski N, Blackwell TS, Van Kaer L, Drake WP. PD-1 up-regulation on CD4+ T cells promotes pulmonary fibrosis through STAT3-mediated IL-17A and TGF-β1 production. Science Translational Medicine 2018, 10 PMID: 30257954, PMCID: PMC6263177, DOI: 10.1126/scitranslmed.aar8356.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAnimalsBleomycinCD4-Positive T-LymphocytesCell ProliferationCollagen Type IDisease Models, AnimalFemaleFibroblastsGene Expression RegulationHumansIdiopathic Pulmonary FibrosisInterleukin-17MaleMiceMiddle AgedProgrammed Cell Death 1 ReceptorRNA, MessengerSarcoidosisSTAT3 Transcription FactorTh17 CellsTransforming Growth Factor beta1Up-RegulationConceptsIdiopathic pulmonary fibrosisPD-1Pulmonary fibrosisT cellsCollagen-1 productionPD-1 pathway blockadeCell death ligand 1T helper 17 (Th17) cellsPD-1 regulationIL-17A expressionProgressive inflammatory diseaseDeath ligand 1Helper 17 cellsT cell subsetsCell death 1Limited therapeutic optionsTGF-β1 productionLung disease pathophysiologyHuman lung fibroblastsPredominant CD4Bleomycin administrationIL-17ADeath-1Therapeutic optionsCell subsets
2017
Application of “Omics” and Systems Biology to Sarcoidosis Research
Crouser ED, Fingerlin TE, Yang IV, Maier LA, Nana-Sinkam P, Collman RG, Kaminski N. Application of “Omics” and Systems Biology to Sarcoidosis Research. Annals Of The American Thoracic Society 2017, 14: s445-s451. PMID: 29053026, PMCID: PMC5822413, DOI: 10.1513/annalsats.201707-567ot.Peer-Reviewed Original ResearchConceptsSystems biology researchBiology researchSystems biologyDistinct genetic mechanismsNumerous genetic mutationsField of sarcoidosisGenetic mechanismsDiverse clinical phenotypesOmicsMechanistic underpinningsComprehensive profilingPolygenic diseaseGenetic mutationsDiverse diseasesBiologyAdvanced computational approachesEnormous data setsComputational approachClinical phenotypeOrganismsPolygenicMutationsDisease-related mortalityPhenotypeLife-altering symptomsTranscriptome profiles in sarcoidosis and their potential role in disease prediction
Schupp JC, Vukmirovic M, Kaminski N, Prasse A. Transcriptome profiles in sarcoidosis and their potential role in disease prediction. Current Opinion In Pulmonary Medicine 2017, 23: 487-492. PMID: 28590292, PMCID: PMC5637542, DOI: 10.1097/mcp.0000000000000403.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsConceptsGenome-wide expression studiesWide expression studiesTranscriptome profilesTranscriptomic dataRNA sequencingExpression studiesGene expressionMolecular mechanismsLarge prospective followTh1 immune responseTranscriptomeNonnecrotizing granulomasProspective followSystemic diseaseDisease progressionTreatment outcomesImmune responseSarcoidosisPotential roleControl tissuesProgressive sarcoidosisKey roleDiseaseTranscriptomicsGranulomas
2015
Rationale and Design of the Genomic Research in Alpha-1 Antitrypsin Deficiency and Sarcoidosis Study. Alpha-1 Protocol
Strange C, Senior RM, Sciurba F, O’Neal S, Morris A, Wisniewski SR, Bowler R, Hochheiser HS, Becich MJ, Zhang Y, Leader JK, Methé BA, Kaminski N, Sandhaus RA, Group* F. Rationale and Design of the Genomic Research in Alpha-1 Antitrypsin Deficiency and Sarcoidosis Study. Alpha-1 Protocol. Annals Of The American Thoracic Society 2015, 12: 1551-1560. PMID: 26153726, PMCID: PMC4627425, DOI: 10.1513/annalsats.201503-143oc.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAged, 80 and overAlpha 1-Antitrypsin DeficiencyBronchoalveolar LavageCross-Sectional StudiesExercise ToleranceFemaleGenomicsGenotypeHumansMaleMicrobiotaMiddle AgedPhenotypeProspective StudiesPulmonary Disease, Chronic ObstructivePulmonary EmphysemaResearch DesignRespiratory Function TestsSarcoidosisTomography, X-Ray ComputedConceptsAlpha-1 antitrypsin deficiencyAugmentation therapyBronchoalveolar lavageAntitrypsin deficiencyClinical presentationPiZZ individualsAlpha-1-antitrypsin augmentation therapyAlpha-1 antitrypsin genotypeChronic obstructive pulmonary disease phenotypesPulmonary function testingAge 35 yearsVariable clinical presentationCross-sectional studyAlpha-1 antitrypsinIntermediate outcome measuresPulmonary disease phenotypesUnique genetic causeExercise capacityTherapeutic trialsChest tomographyClinical symptomsCOPD pathogenesisCOPD phenotypesFunction testingCOPD StudyRationale and Design of the Genomic Research in Alpha-1 Antitrypsin Deficiency and Sarcoidosis (GRADS) Study. Sarcoidosis Protocol
Moller DR, Koth LL, Maier LA, Morris A, Drake W, Rossman M, Leader JK, Collman RG, Hamzeh N, Sweiss NJ, Zhang Y, O’Neal S, Senior RM, Becich M, Hochheiser HS, Kaminski N, Wisniewski SR, Gibson KF, Group* F. Rationale and Design of the Genomic Research in Alpha-1 Antitrypsin Deficiency and Sarcoidosis (GRADS) Study. Sarcoidosis Protocol. Annals Of The American Thoracic Society 2015, 12: 1561-1571. PMID: 26193069, PMCID: PMC4627423, DOI: 10.1513/annalsats.201503-172ot.Peer-Reviewed Original ResearchConceptsAlpha-1 antitrypsin deficiencyClinical courseLung microbiomeAntitrypsin deficiencyClinical heterogeneityPathobiology of sarcoidosisTremendous clinical heterogeneityObservational cohort studyPulmonary function testsSystemic inflammatory responsePeripheral blood changesDiagnosis of sarcoidosisSelf-administered questionnaireCohort studyBaseline visitBronchoalveolar lavageFunction testsGranulomatous inflammationSystemic diseaseSarcoidosis phenotypesUrine testingClinical bronchoscopyInflammatory responseSarcoidosis StudyPrognostic biomarkerSolving the Conundrum: Immunogenetics of Sarcoidosis
Kaminski N, Drake WP. Solving the Conundrum: Immunogenetics of Sarcoidosis. American Journal Of Respiratory And Critical Care Medicine 2015, 192: 652-654. PMID: 26371809, PMCID: PMC4595685, DOI: 10.1164/rccm.201506-1235ed.Peer-Reviewed Original Research
2013
Oral Antimycobacterial Therapy in Chronic Cutaneous Sarcoidosis: A Randomized, Single-Masked, Placebo-Controlled Study
Drake WP, Oswald-Richter K, Richmond BW, Isom J, Burke VE, Algood H, Braun N, Taylor T, Pandit KV, Aboud C, Yu C, Kaminski N, Boyd AS, King LE. Oral Antimycobacterial Therapy in Chronic Cutaneous Sarcoidosis: A Randomized, Single-Masked, Placebo-Controlled Study. JAMA Dermatology 2013, 149: 1040-1049. PMID: 23863960, PMCID: PMC3927541, DOI: 10.1001/jamadermatol.2013.4646.Peer-Reviewed Original ResearchMeSH KeywordsAdministration, OralAdultAgedAnti-Bacterial AgentsAzithromycinCD4-Positive T-LymphocytesChronic DiseaseDrug Therapy, CombinationEthambutolFemaleFollow-Up StudiesHumansLevofloxacinMaleMiddle AgedOfloxacinRifampinSarcoidosisSeverity of Illness IndexSingle-Blind MethodSkin DiseasesTranscriptomeTreatment OutcomeYoung AdultConceptsChronic cutaneous sarcoidosisCutaneous sarcoidosis lesionsAntimycobacterial therapyLesion diameterCutaneous sarcoidosisSarcoidosis lesionsDisease severityPlacebo-controlled studyPlacebo-treated groupCompletion of therapyT cell functionChronic granulomatous diseaseT cell receptor stimulationSignificant reductionConcomitant levofloxacinPlacebo regimenRifampin regimenSingle-MaskedPlacebo groupTreat analysisDermatology centersTherapeutic optionsGranulomatous diseaseT cellsLesion severity