2024
“Deficiency in ELF4, X-Linked”: a Monogenic Disease Entity Resembling Behçet’s Syndrome and Inflammatory Bowel Disease
Olyha S, O’Connor S, Kribis M, Bucklin M, Uthaya Kumar D, Tyler P, Alam F, Jones K, Sheikha H, Konnikova L, Lakhani S, Montgomery R, Catanzaro J, Du H, DiGiacomo D, Rothermel H, Moran C, Fiedler K, Warner N, Hoppenreijs E, van der Made C, Hoischen A, Olbrich P, Neth O, Rodríguez-Martínez A, Lucena Soto J, van Rossum A, Dalm V, Muise A, Lucas C. “Deficiency in ELF4, X-Linked”: a Monogenic Disease Entity Resembling Behçet’s Syndrome and Inflammatory Bowel Disease. Journal Of Clinical Immunology 2024, 44: 44. PMID: 38231408, PMCID: PMC10929603, DOI: 10.1007/s10875-023-01610-8.Peer-Reviewed Original ResearchConceptsDEX patientsClass-switched memory B cellsInborn errors of immunityTreated with anti-inflammatory agentsLow natural killerX-linkedMemory B cellsErrors of immunityCohort of patientsIncreased inflammatory cytokinesLoss-of-function variantsHeterogeneous clinical phenotypesInflammatory bowel diseaseTargeted therapeutic interventionsNatural killerAnti-inflammatory agentsAphthous ulcersTherapeutic responseAutoinflammatory syndromeInflammatory markersClinical manifestationsB cellsBehcet's syndromeGastrointestinal symptomsMechanisms of disease
2021
Small intestinal immunopathology and GI-associated antibody formation in hereditary alpha-tryptasemia
Konnikova L, Robinson TO, Owings AH, Shirley JF, Davis E, Tang Y, Wall S, Li J, Hasan MH, Gharaibeh RZ, Mendoza Alvarez LB, Ryan LK, Doty A, Chovanec JF, O'Connell MP, Grunes DE, Daley WP, Mayer E, Chang L, Liu J, Snapper SB, Milner JD, Glover SC, Lyons JJ. Small intestinal immunopathology and GI-associated antibody formation in hereditary alpha-tryptasemia. Journal Of Allergy And Clinical Immunology 2021, 148: 813-821.e7. PMID: 33865872, PMCID: PMC9017395, DOI: 10.1016/j.jaci.2021.04.004.Peer-Reviewed Original ResearchConceptsClass-switched memory B cellsMemory B cellsB cellsSyndrome cohortCell pyroptosisFunctional GI diseasesQuiescent Crohn's diseaseSmall intestinal immunopathologySubclinical intestinal inflammationFunctional gastrointestinal symptomsMast cell numbersTissue mast cellsExpression of CD203cBasal serum tryptaseElevated basal serum tryptaseIntestinal immunopathologyGastrointestinal symptomsImmunologic findingsIntestinal inflammationCrohn's diseaseHLA-DRSmall bowelGI diseaseIgG reactiveImmunologic characteristics
2020
In utero human intestine harbors unique metabolomic features including bacterial metabolites
Li Y, Toothaker JM, Ben-Simon S, Ozeri L, Schweitzer R, McCourt BT, McCourt CC, Werner L, Snapper SB, Shouval DS, Khatib S, Koren O, Agnihorti S, Tseng G, Konnikova L. In utero human intestine harbors unique metabolomic features including bacterial metabolites. JCI Insight 2020, 5: e138751. PMID: 33001863, PMCID: PMC7710283, DOI: 10.1172/jci.insight.138751.Peer-Reviewed Original ResearchConceptsFetal immune systemIntestinal barrier integrityMicrobial-associated metabolitesHost-derived metabolitesBacterial DNAIntestinal immunityMaternal microbiomeIntestinal functionImmune regulationGastrointestinal tractIntestinal microbiomeFetal intestineBarrier integrityImmune systemHuman intestinal samplesIntestinal samplesIntestinal profileMicrobial encountersMetabolomic featuresBacterial metabolitesUteroNutrient metabolismMetabolitesRecent studiesMicrobiomeThe Protective Effects of Calcineurin on Pancreatitis in Mice Depend on the Cellular Source
Wen L, Javed TA, Dobbs AK, Brown R, Niu M, Li L, Khalid A, Barakat M, Xiao X, Yimlamai D, Konnikova L, Yu M, Byersdorfer CA, Husain SZ. The Protective Effects of Calcineurin on Pancreatitis in Mice Depend on the Cellular Source. Gastroenterology 2020, 159: 1036-1050.e8. PMID: 32445858, PMCID: PMC7502475, DOI: 10.1053/j.gastro.2020.05.051.Peer-Reviewed Original ResearchMeSH KeywordsAcinar CellsAcute Lung InjuryAnimalsBone Marrow CellsCalcineurinCalcineurin InhibitorsCalcium-Binding ProteinsCells, CulturedCeruletideCytokinesDisease Models, AnimalFemaleHumansMaleMiceMice, TransgenicMuscle ProteinsNeutrophilsNFATC Transcription FactorsPancreasPancreatitisPrimary Cell CultureConceptsAdministration of caeruleinLocal pancreatic inflammationBiliopancreatic ductPancreas-specific deletionLung inflammationPancreatic inflammationAcute pancreatitisControl miceNeutrophil chemotaxisProtective effectHematopoietic-specific deletionPancreatic acinar cell necrosisPrevention of pancreatitisLevels of cytokinesAcinar cell necrosisSwiss Webster miceActivated T cellsAdeno-associated virus vectorPrimary pancreatic acinar cellsReactive oxygen species productionNFAT-luciferaseSevere pancreatitisCalcineurin inhibitorsNeutrophil expressionPancreatic acinar cellsSingle-Cell Analyses of Colon and Blood Reveal Distinct Immune Cell Signatures of Ulcerative Colitis and Crohn’s Disease
Mitsialis V, Wall S, Liu P, Ordovas-Montanes J, Parmet T, Vukovic M, Spencer D, Field M, McCourt C, Toothaker J, Bousvaros A, Center B, Ballal S, Bonilla S, Fawaz R, Fishman L, Flores A, Fox V, Grover A, Higuchi L, Huh S, Kahn S, Lee C, Mobassaleh M, Ouahed J, Pleskow R, Regan B, Rufo P, Sabharwal S, Silverstein J, Verhave M, Wolf A, Zimmerman L, Zitomersky N, Center B, Allegretti J, De Silva P, Friedman S, Hamilton M, Korzenik J, Makrauer F, Norton B, Winter R, Shalek A, Kean L, Horwitz B, Goldsmith J, Tseng G, Snapper S, Konnikova L. Single-Cell Analyses of Colon and Blood Reveal Distinct Immune Cell Signatures of Ulcerative Colitis and Crohn’s Disease. Gastroenterology 2020, 159: 591-608.e10. PMID: 32428507, PMCID: PMC8166295, DOI: 10.1053/j.gastro.2020.04.074.Peer-Reviewed Original ResearchConceptsInflammatory bowel diseasePeripheral blood mononuclear cellsActive Crohn's diseaseBlood mononuclear cellsColonic mucosa samplesActive ulcerative colitisPlasmacytoid dendritic cellsInnate lymphoid cellsUlcerative colitisCrohn's diseaseDendritic cellsImmune cell populationsRegulatory cellsMononuclear cellsT cellsMucosa samplesBlood samplesLymphoid cellsGroup 1 innate lymphoid cellsType 3 innate lymphoid cellsEffector memory T cellsCell populationsInactive ulcerative colitisInactive Crohn's diseaseMemory T cellsRole of Nutrition in Prevention of Neonatal Spontaneous Intestinal Perforation and Its Complications: A Systematic Review
Olaloye O, Swatski M, Konnikova L. Role of Nutrition in Prevention of Neonatal Spontaneous Intestinal Perforation and Its Complications: A Systematic Review. Nutrients 2020, 12: 1347. PMID: 32397283, PMCID: PMC7284579, DOI: 10.3390/nu12051347.Peer-Reviewed Original ResearchMeSH KeywordsEatingEnteral NutritionFeeding MethodsFemaleHumansInfant, Extremely Low Birth WeightInfant, NewbornIntestinal PerforationLength of StayMaleNeurodevelopmental DisordersNutritional Physiological PhenomenaParenteral NutritionPostoperative CarePostoperative ComplicationsSpontaneous PerforationTime FactorsConceptsSpontaneous intestinal perforationIncidence of SIPRole of nutritionEnteral nutritionIntestinal perforationFeeding practicesSystematic reviewEarly enteral nutritionFull enteral feedsPost-operative nutritionLow birthweight infantsLength of stayHistorical control studySearch of PubMedDays of lifeMeta-Analyses (PRISMA) guidelinesPreferred Reporting ItemsRelevant search termsELBW infantsNutrition initiationCohort studyDevastating complicationParenteral nutritionSecondary outcomesEnteral feeds
2019
A Unique Presentation of Infantile-Onset Colitis and Eosinophilic Disease without Recurrent Infections Resulting from a Novel Homozygous CARMIL2 Variant
Kurolap A, Eshach Adiv O, Konnikova L, Werner L, Gonzaga-Jauregui C, Steinberg M, Mitsialis V, Mory A, Nunberg MY, Wall S, Shaoul R, Overton JD, Shuldiner A, Zohar Y, Paperna T, Snapper S, Shouval D, Baris Feldman H. A Unique Presentation of Infantile-Onset Colitis and Eosinophilic Disease without Recurrent Infections Resulting from a Novel Homozygous CARMIL2 Variant. Journal Of Clinical Immunology 2019, 39: 430-439. PMID: 31079270, DOI: 10.1007/s10875-019-00631-6.Peer-Reviewed Original ResearchMeSH KeywordsAge of OnsetAmino Acid SequenceChildChild, PreschoolColitisDNA Mutational AnalysisEnteritisEosinophiliaExome SequencingGastritisGenetic Association StudiesGenetic Predisposition to DiseaseHomozygoteHumansImmunohistochemistryImmunophenotypingMaleMicrofilament ProteinsModels, MolecularMutationPhenotypeStructure-Activity RelationshipConceptsWhole-exome sequencingImmunological workupWestern blotRecurrent infectionsGastrointestinal diseasesCyTOF analysisRegulatory T cell frequencyEosinophilic gastrointestinal diseasesEosinophilic gastrointestinal disordersT cell frequenciesUlcerative colitis patientsAdaptive immune cellsEvidence of recurrentSigns of immunodeficiencyT cell proliferationT-cell studiesColitis patientsChronic diarrheaImmunodeficiency syndromeTreg generationGastrointestinal disordersImmunological phenotypeImmune populationsImmune cellsSevere infections
2018
Human TGF-β1 deficiency causes severe inflammatory bowel disease and encephalopathy
Kotlarz D, Marquardt B, Barøy T, Lee WS, Konnikova L, Hollizeck S, Magg T, Lehle AS, Walz C, Borggraefe I, Hauck F, Bufler P, Conca R, Wall SM, Schumacher EM, Misceo D, Frengen E, Bentsen BS, Uhlig HH, Hopfner KP, Muise AM, Snapper SB, Strømme P, Klein C. Human TGF-β1 deficiency causes severe inflammatory bowel disease and encephalopathy. Nature Genetics 2018, 50: 344-348. PMID: 29483653, PMCID: PMC6309869, DOI: 10.1038/s41588-018-0063-6.Peer-Reviewed Original ResearchConceptsInfantile inflammatory bowel diseaseInflammatory bowel diseaseTGF-β1Bowel diseaseSevere inflammatory bowel diseaseCentral nervous system diseaseNervous system diseasesRole of TGFPosterior leukoencephalopathyIntestinal immunityBrain atrophySystem diseasesTGFB1 geneBiallelic lossImpaired secretionGrowth factorTGF-β familyDiseaseTGF-β1 deficiencyNonredundant roleFunction mutationsPrototypic memberLeukoencephalopathyAtrophyEpilepsy
2017
An algorithm for the classification of mRNA patterns in eosinophilic esophagitis: Integration of machine learning
Sallis BF, Erkert L, Moñino-Romero S, Acar U, Wu R, Konnikova L, Lexmond WS, Hamilton MJ, Dunn WA, Szepfalusi Z, Vanderhoof JA, Snapper SB, Turner JR, Goldsmith JD, Spencer LA, Nurko S, Fiebiger E. An algorithm for the classification of mRNA patterns in eosinophilic esophagitis: Integration of machine learning. Journal Of Allergy And Clinical Immunology 2017, 141: 1354-1364.e9. PMID: 29273402, PMCID: PMC6425755, DOI: 10.1016/j.jaci.2017.11.027.Peer-Reviewed Original ResearchMeSH KeywordsAdolescentAlgorithmsChildChild, PreschoolDecision Support Systems, ClinicalDecision Support TechniquesEosinophilic EsophagitisFactor Analysis, StatisticalFemaleGenetic MarkersHumansImmunohistochemistryInfantMachine LearningMaleRegistriesRNA, MessengerSensitivity and SpecificitySingle-Blind MethodConceptsAllergic statusEosinophilic esophagitisPatient's allergic statusGastroesophageal reflux diseaseBiopsies of patientsEpsilon germ-line transcriptsEoE patientsReflux diseaseAllergic inflammationIgE productionSerum IgEEquivocal patientsPatient subpopulationsDiagnostic evaluationIndividualized therapyEquivocal casesPrimary analysisPatient careGerm-line transcriptsEoEPatientsDiagnostic precisionEsophagitisScoresTherapyEnhanced TH17 Responses in Patients with IL10 Receptor Deficiency and Infantile-onset IBD
Shouval DS, Konnikova L, Griffith AE, Wall SM, Biswas A, Werner L, Nunberg M, Kammermeier J, Goettel JA, Anand R, Chen H, Weiss B, Li J, Loizides A, Yerushalmi B, Yanagi T, Beier R, Conklin LS, Ebens CL, Santos FGMS, Sherlock M, Goldsmith JD, Kotlarz D, Glover SC, Shah N, Bousvaros A, Uhlig HH, Muise AM, Klein C, Snapper SB. Enhanced TH17 Responses in Patients with IL10 Receptor Deficiency and Infantile-onset IBD. Inflammatory Bowel Diseases 2017, 23: 1950-1961. PMID: 29023267, DOI: 10.1097/mib.0000000000001270.Peer-Reviewed Original ResearchConceptsT cell proliferationDeficient patientsTh17 cellsReceptor deficiencySevere infantile-onset inflammatory bowel diseaseInfantile-onset inflammatory bowel diseaseAdaptive immune cell functionsCD4 T cell functionCD4 T cell proliferationCD4 T cell subsetsHematopoietic stem cell transplantationPeripheral blood mononuclear cellsNaive T cell proliferationSuppression of TregsGeneration of TregsInflammatory bowel diseaseRegulatory T cellsStem cell transplantationT cell subsetsBlood mononuclear cellsImmune cell defectsAnti-inflammatory macrophagesT cell functionImmune cell functionReal-time polymerase chain reaction
2012
The Role of Pulmonary Follow-up in Reducing Health Care Utilization in Infants With Bronchopulmonary Dysplasia
Rhein LM, Konnikova L, McGeachey A, Pruchniewski M, Smith VC. The Role of Pulmonary Follow-up in Reducing Health Care Utilization in Infants With Bronchopulmonary Dysplasia. Clinical Pediatrics 2012, 51: 645-650. PMID: 22492835, DOI: 10.1177/0009922812439242.Peer-Reviewed Original ResearchConceptsRate of rehospitalizationHealth care utilizationPreterm infantsBronchopulmonary dysplasiaED visitsEmergency departmentCare utilizationNeonatal intensive care unitMore supplemental oxygenRole of PulmonaryRetrospective cohort studyIntensive care unitSevere lung diseaseTime of dischargeChildren's Hospital BostonRate of visitsElectronic medical recordsExpected higher rateNeurodevelopmental followCohort studyWeeks' gestationCare unitOutpatient visitsRespiratory causesSupplemental oxygen