ABSTRACT
AIM: A20 haploinsufficiency (HA20) is a recently described autoinflammatory disease that manifests symptoms similar to those of Behçet's disease. However, little is known about the involvement of the liver in HA20. Here, we report a case of HA20 complicated by autoimmune hepatitis (AIH). CASE PRESENTATION: A 33-year-old woman was previously diagnosed with HA20 and chronic thyroiditis, and was treated with prednisolone (PSL; 7.5 mg/day) and levothyroxine sodium hydrate (125 µg/day). She experienced general malaise and jaundice, and biochemical evaluation revealed elevated liver function with an aspartate aminotransferase level of 817 U/L, an alanine aminotransferase level of 833 U/L, and a total bilirubin of 8.3 mg/dL. Pathological evaluation of the liver biopsy revealed interface hepatitis and the patient was diagnosed with acute exacerbation of AIH. Upon increasing the PSL dose to 60 mg/day, the liver enzyme levels rapidly decreased. During tapering of PSL, azathioprine 50 mg/day was added, and there was no relapse of AIH with combination therapy of PSL 7 mg/day and azathioprine 50 mg/day. CONCLUSION: This is the first report of biopsy-proven AIH in an Asian patient with HA20. This case has significant implications for the pathogenesis and treatment of AIH in patients with HA20.
ABSTRACT
The endoplasmic reticulum (ER) plays a pivotal role in cellular functions such as the ER stress response. However, the effect of the ER membrane on caspase activation remains unclear. This study reveals that polyglutamine oligomers augmented at ER induce insertion of Bax into the ER membrane, thereby activating caspase-7. In line with the role of ER in cell death induced by polyglutamine expansion, the ER membrane was found to be disrupted and dilated in the brain of a murine model of Huntington's disease. We can conclude that polyglutamine expansion may drive caspase-7 activation by disrupting the ER membrane.
