Publication:
A novel insight into the pathophysiology of autoimmune hepatitis: an immune activator mutation in the FLT3 receptor

dc.contributor.departmentKUTTAM (Koç University Research Center for Translational Medicine)
dc.contributor.departmentKUH (Koç University Hospital)
dc.contributor.kuauthorArmutlu, Ayşe
dc.contributor.kuauthorYüksel, Muhammed
dc.contributor.kuauthorNazmi, Farinaz
dc.contributor.kuauthorArıkan, Çiğdem
dc.contributor.kuprofileTeaching Faculty
dc.contributor.kuprofileFaculty Member
dc.contributor.yokid133567
dc.contributor.yokidN/A
dc.contributor.yokidN/A
dc.contributor.yokid240198
dc.date.accessioned2024-11-09T13:47:25Z
dc.date.issued2021
dc.description.abstractAutoimmune hepatitis (AIH) is a chronic progressive autoimmune liver disease characterized by hypergammaglobulinemia, interface hepatitis, a female preponderance, and the presence of autoantibodies in most patients. The presence of HLA-DR3/DR4 and functional impairment in regulatory T cells are associated with AIH. However, AIH is a multifactorial complex disease. This report is a description of a case of seronegative AIH in a girl with chronic hepatitis, a high immunoglobulin E (IgE) level, perforating nodular dermatitis, and sheer eosinophilia. To re-evaluate the diagnosis, whole exon sequencing was performed. It was determined that the patient had ancestral haplotype A1-B8-DR3, which is associated with autoimmunity. Importantly, it was also noted that an undocumented point mutation (Ala627Thr) of the FMS-like tyrosine 3 kinase (FLT3) receptor was present. This FLT3 receptor gain-of-function mutation is associated with the activation of the mechanistic target of rapamycin (mTOR), and dendritic cell activation. In addition, a loss-of-function mutation in the melanocortin-3 receptor gene, which inhibits interleukin 4, was detected. The constellation of these immune deregulatory factors may have propagated auto-aggression of the liver, causing chronic hepatitis with AIH features. The findings of seronegativity with eosinophilia and a high IgE level led us to hypothesize that the pathognomonic mechanism in this case was unlike that of classic AIH pathophysiology. Since mTOR is constitutively activated, mTOR inhibitors may be a useful option to treat AIH and dermatitis.
dc.description.fulltextYES
dc.description.indexedbyWoS
dc.description.indexedbyPubMed
dc.description.issue3
dc.description.openaccessYES
dc.description.publisherscopeNational
dc.description.sponsoredbyTubitakEuN/A
dc.description.sponsorshipN/A
dc.description.versionPublisher version
dc.description.volume2
dc.formatpdf
dc.identifier.doi10.14744/hf.2021.2021.0010
dc.identifier.embargoNO
dc.identifier.filenameinventorynoIR03916
dc.identifier.issn1307-5888
dc.identifier.linkhttps://doi.org/10.14744/hf.2021.2021.0010
dc.identifier.quartileN/A
dc.identifier.scopus2-s2.0-85164361933
dc.identifier.urihttps://hdl.handle.net/20.500.14288/3766
dc.identifier.wos863551100006
dc.keywordsAutoimmune hepatitis
dc.keywordsLiver disease
dc.keywordsMutation
dc.languageEnglish
dc.publisherKare Yayıncılık
dc.relation.grantnoNA
dc.relation.urihttp://cdm21054.contentdm.oclc.org/cdm/ref/collection/IR/id/10777
dc.sourceHepatology Forum
dc.subjectMedicine
dc.titleA novel insight into the pathophysiology of autoimmune hepatitis: an immune activator mutation in the FLT3 receptor
dc.typeJournal Article
dspace.entity.typePublication
local.contributor.authorid0000-0001-9804-0454
local.contributor.authoridN/A
local.contributor.authoridN/A
local.contributor.authorid0000-0002-0794-2741
local.contributor.kuauthorArmutlu, Ayşe
local.contributor.kuauthorYüksel, Muhammed
local.contributor.kuauthorNazmi, Farinaz
local.contributor.kuauthorArıkan, Çiğdem
local.publication.orgunit1SCHOOL OF MEDICINE
local.publication.orgunit2KUTTAM (Koç University Research Center for Translational Medicine)
local.publication.orgunit2KUH (Koç University Hospital)
relation.isOrgUnitOfPublication91bbe15d-017f-446b-b102-ce755523d939
relation.isOrgUnitOfPublicationf91d21f0-6b13-46ce-939a-db68e4c8d2ab
relation.isOrgUnitOfPublication.latestForDiscovery91bbe15d-017f-446b-b102-ce755523d939

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