PMID- 35784907
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20220716
IS  - 2757-7392 (Electronic)
IS  - 1307-5888 (Print)
IS  - 2757-7392 (Linking)
VI  - 2
IP  - 3
DP  - 2021 Sep
TI  - A novel insight into the pathophysiology of autoimmune hepatitis: An immune 
      activator mutation in the FLT3 receptor.
PG  - 112-116
LID - 10.14744/hf.2021.2021.0010 [doi]
AB  - Autoimmune 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.
CI  - (c) Copyright 2021 by Hepatology Forum - Available online at 
      www.hepatologyforum.org.
FAU - Yuksel, Muhammed
AU  - Yuksel M
AUID- ORCID: 0000-0002-3390-6007
AD  - Paediatric Gastroenterology-Hepatology/Liver Transplantation Centre, Koc 
      University, Istanbul, Turkey.
AD  - Research Centre for Translational Medicine (KUTTAM)-Liver Immunology Laboratory, 
      Koc University, Istanbul, Turkey.
FAU - Armutlu, Ayse
AU  - Armutlu A
AUID- ORCID: 0000-0001-9804-0454
AD  - Department of Pathology, Koc University Hospital, Istanbul, Turkey.
FAU - Nazmi, Farinaz
AU  - Nazmi F
AUID- ORCID: 0000-0001-6245-5789
AD  - Paediatric Gastroenterology-Hepatology/Liver Transplantation Centre, Koc 
      University, Istanbul, Turkey.
AD  - Research Centre for Translational Medicine (KUTTAM)-Liver Immunology Laboratory, 
      Koc University, Istanbul, Turkey.
FAU - Ceylaner, Serdar
AU  - Ceylaner S
AUID- ORCID: 0000-0003-2786-1911
AD  - Intergen Diagnostic Centre for Genetic Disorders, Ankara, Turkey.
FAU - Arikan, Cigdem
AU  - Arikan C
AUID- ORCID: 0000-0002-0794-2741
AD  - Paediatric Gastroenterology-Hepatology/Liver Transplantation Centre, Koc 
      University, Istanbul, Turkey.
AD  - Research Centre for Translational Medicine (KUTTAM)-Liver Immunology Laboratory, 
      Koc University, Istanbul, Turkey.
LA  - eng
PT  - Case Reports
DEP - 20210907
PL  - Turkey
TA  - Hepatol Forum
JT  - Hepatology forum
JID - 9918351171306676
PMC - PMC9138941
OTO - NOTNLM
OT  - Autoimmune hepatitis
OT  - liver disease
OT  - mutation
COIS- Conflict of Interest: The authors have no conflict of interest to declare.
EDAT- 2022/07/06 06:00
MHDA- 2022/07/06 06:01
PMCR- 2021/09/07
CRDT- 2022/07/05 10:32
PHST- 2021/04/08 00:00 [received]
PHST- 2021/05/26 00:00 [accepted]
PHST- 2022/07/05 10:32 [entrez]
PHST- 2022/07/06 06:00 [pubmed]
PHST- 2022/07/06 06:01 [medline]
PHST- 2021/09/07 00:00 [pmc-release]
AID - hf-2-112 [pii]
AID - 10.14744/hf.2021.2021.0010 [doi]
PST - epublish
SO  - Hepatol Forum. 2021 Sep 7;2(3):112-116. doi: 10.14744/hf.2021.2021.0010. 
      eCollection 2021 Sep.