Yuksel, Muhammed, Armutlu, Ayse, Nazmi, Farinaz, Ceylaner, Serdar and Arikan, Cigdem 2021. A novel insight into the pathophysiology of autoimmune hepatitis: An immune activator mutation in the FLT3 receptor. Hepatology Forum. 2 (3), pp. 112-116. https://doi.org/10.14744/hf.2021.2021.0010
| Title | A novel insight into the pathophysiology of autoimmune hepatitis: An immune activator mutation in the FLT3 receptor |
|---|---|
| Type | Journal article |
| Authors | Yuksel, Muhammed, Armutlu, Ayse, Nazmi, Farinaz, Ceylaner, Serdar and Arikan, Cigdem |
| Abstract | Autoimmune hepatitis (AIH) is a chronic progressive autoimmune liver disease characterized by hypergammaglobulinemia, interface hepatitis, female preponderance and presence of autoantibodies in most patients. The presence of HLA-DR3/DR4 and functional impairments in regulatory T cells are associated with AIH. However, AIH is a multifactorial complex disease. In this report, we present a case of a seronegative AIH girl with chronic hepatitis, hyper-IgE, perforating nodular dermatitis and sheer eosinophilia. To re-evaluate the diagnosis, whole exon sequencing was performed. We determined that the patient has the ancestral haplotype A1-B8-DR3 associated with autoimmunity. More importantly, we found an undocumented point mutation (Ala627Thr) of the FMS-like-tyrosine 3 kinase (FLT3) receptor. This FLT3 receptor gain-of-function mutation is associated with the activation of the mammalian target of rapamycin (mTOR) instigating dendritic cell activation. Furthermore, a loss-of-function mutation in the melanocortin-3 receptor (MC3R) gene paramount in inhibiting IL4 was detected. The constellation of these immune deregulatory factors may have propagated auto-aggression of the liver causing chronic hepatitis with AIH features. Albeit, the seronegativity with eosinophilia and hyper-IgE let us hypothesize that the pathognomonic mechanisms, in this case, diverts from classical AIH pathophysiology. As mTOR is constitutively activated, mTOR inhibitors may be used to treat AIH and dermatitis. |
| Journal | Hepatology Forum |
| Journal citation | 2 (3), pp. 112-116 |
| Year | 2021 |
| Publisher | Turkish Association for the Study of the Liver |
| Publisher's version | License CC BY-NC 4.0 File Access Level Open (open metadata and files) |
| Digital Object Identifier (DOI) | https://doi.org/10.14744/hf.2021.2021.0010 |
| Publication dates | |
| Published | 07 Sep 2021 |