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
2022
RIPK1 mutations causing infantile-onset IBD with inflammatory and fistulizing features
Sultan M, Adawi M, Kol N, McCourt B, Adawi I, Baram L, Tal N, Werner L, Lev A, Snapper S, Barel O, Konnikova L, Somech R, Shouval D. RIPK1 mutations causing infantile-onset IBD with inflammatory and fistulizing features. Frontiers In Immunology 2022, 13: 1041315. PMID: 36466854, PMCID: PMC9716469, DOI: 10.3389/fimmu.2022.1041315.Peer-Reviewed Original ResearchConceptsInfantile-onset inflammatory bowel diseaseReceptor-interacting serine/threonine-protein kinase 1Serine/threonine-protein kinase 1Peripheral blood mononuclear cellsRole of RIPK1Immune cellsMultiple cell typesRIPK1 deficiencyKinase domainCrohn's diseasePatient 1Patient 2Perianal fistulasT cellsGenetic analysisProtein modelingKinase 1B cellsGenetic studiesAllogeneic hematopoietic stem cell transplantationPatients' peripheral blood mononuclear cellsImportant regulatorHematopoietic stem cell transplantationPathogenic genetic variantsCell typesDOP64 Pathogenic RIPK1 Mutations Cause Infantile-onset IBD with Inflammatory and Fistulizing Features
Sultan M, Millman P, McCourt B, Kol N, Lev A, Matar M, Barel O, Shamir R, Wilschanski M, Konnikova L, Somech R, Shouval D. DOP64 Pathogenic RIPK1 Mutations Cause Infantile-onset IBD with Inflammatory and Fistulizing Features. Journal Of Crohn's And Colitis 2022, 16: i109-i109. DOI: 10.1093/ecco-jcc/jjab232.103.Peer-Reviewed Original ResearchInfantile-onset inflammatory bowel diseaseInflammatory bowel diseasePeripheral blood mononuclear cellsImmune cellsMass cytometry timePerianal fistulasCytometry timeSevere infantile-onset inflammatory bowel diseaseB cellsAllogeneic hematopoietic stem cell transplantationPatients' peripheral blood mononuclear cellsSevere inflammatory bowel diseaseHematopoietic stem cell transplantationIL-1 receptor antagonistMultiple perianal fistulasHyper-inflammatory responseIntestinal immune responsePatient's immune cellsStem cell transplantationBlood mononuclear cellsPeripheral immune dysregulationIL-6 productionRole of RIPK1Cytokine secretion analysisSanger sequencing
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
2019
Maturation of the Human Intestinal Immune System Occurs Early in Fetal Development
Stras SF, Werner L, Toothaker JM, Olaloye OO, Oldham AL, McCourt CC, Lee YN, Rechavi E, Shouval DS, Konnikova L. Maturation of the Human Intestinal Immune System Occurs Early in Fetal Development. Developmental Cell 2019, 51: 357-373.e5. PMID: 31607651, DOI: 10.1016/j.devcel.2019.09.008.Peer-Reviewed Original ResearchMeSH KeywordsB-LymphocytesCell ProliferationClone CellsCytokinesFemaleFetal DevelopmentFetusHumansImmune SystemImmunity, MucosalImmunologic MemoryImmunophenotypingInfant, NewbornIntestinesPregnancyPregnancy Trimester, SecondReceptors, Antigen, B-CellReceptors, Antigen, T-CellT-LymphocytesV(D)J RecombinationConceptsInnate lymphoid cellsGestational ageIntestinal immunityDendritic cellsB cellsHuman intestinal immune systemAdaptive immune landscapeIntestinal immune systemNatural killer cellsWeeks gestational ageTransitional B cellsB cell maturityT cell receptorComplex innateImmune atlasEarly life developmentImmune landscapeKiller cellsTCR repertoireLymphoid cellsFetal developmentImmune systemInnate immunityCell receptorMass cytometryHigh-dimensional immune atlas of second trimester human intestinal immunity
Konnikova L, Stras S, Werner L, Toothaker J, Oldham A, Shouval D. High-dimensional immune atlas of second trimester human intestinal immunity. The Journal Of Immunology 2019, 202: 67.12-67.12. DOI: 10.4049/jimmunol.202.supp.67.12.Peer-Reviewed Original ResearchT cellsImmune atlasIntestinal immunityB cellsImmune systemTissue-resident memory T cellsLarge intestineResident memory T cellsMucosal immune developmentNeonatal immune systemEffector memory subsetsInnate lymphoid cellsMemory T cellsNatural killer cellsTransitional B cellsT cell receptorFull-term samplesMost newbornsWeeks' gestationAdvanced gestationKiller cellsMucosal immunityNeonatal deathMemory subsetsImmune cells