Severe Liver Disorder Following Liver Transplantation in STING-Associated Vasculopathy with Onset in Infancy

• Published in: Journal of clinical immunology 2021-07, Vol.41 (5), p.967-974
• Main Authors: Ishikawa, Takashi, Tamura, Eiichiro, Kasahara, Mureo, Uchida, Hajime, Higuchi, Masataka, Kobayashi, Hisato, Shimizu, Hirotaka, Ogawa, Eiki, Yotani, Nobuyuki, Irie, Rie, Kosaki, Rika, Kosaki, Kenjiro, Uchiyama, Toru, Onodera, Masafumi, Kawai, Toshinao
• Format: Article
• Language: English
• Subjects: Age; Antibiotics; Bile ducts; Biomedical and Life Sciences; Biomedicine; Bronchitis; Bronchodilators; Child, Preschool; Cholangitis; Cysts; Female; Gain of Function Mutation; Genetic analysis; Graft rejection; Hepatocytes; Humans; Immunology; Infectious Diseases; Inflammation; Internal Medicine; Liver - pathology; Liver diseases; Liver Diseases - genetics; Liver Diseases - pathology; Liver Diseases - therapy; Liver transplantation; Liver Transplantation - adverse effects; Liver transplants; Medical Microbiology; Membrane Proteins - genetics; Original Article; Vascular diseases; Vascular Diseases - genetics; Vascular Diseases - pathology; Vascular Diseases - therapy; Vasculitis
• ISSN: 0271-9142; 1573-2592
• DOI: 10.1007/s10875-021-00977-w

Purpose STING-associated vasculopathy with onset in infancy (SAVI) is a type-I interferonopathy, characterized by systemic inflammation, peripheral vascular inflammation, and pulmonary manifestations. There are three reports of SAVI patients developing liver disease, but no report of a SAVI patient requiring liver transplantation. Therefore, the relevance of liver inflammation is unclear in SAVI. We report a SAVI patient who developed severe liver disorder following liver transplantation. Methods SAVI was diagnosed in a 4-year-old girl based on genetic analysis by whole-exome sequencing. We demonstrated clinical features, laboratory findings, and pathological examination of her original and transplanted livers. Results At 2 months of age, she developed bronchitis showing resistance to bronchodilators and antibiotics. At 10 months of age, she developed liver dysfunction with atypical cholangitis, which required liver transplantation at 1 year of age. At 2 years of age, multiple biliary cysts developed in the transplanted liver. At 3.9 years of age, SAVI was diagnosed by whole-exome sequencing. Inflammatory cells from the liver invaded the stomach wall directly, leading to fatal gastrointestinal bleeding unexpectedly at 4.6 years of age. In pathological findings, there were no typical findings of liver abscess, vasculitis, or graft rejection, but biliary cysts and infiltration of inflammatory cells, including plasmacytes around the bile duct area, in the transplanted liver were noted, which were findings similar to those of her original liver. Conclusion Although further studies to clarify the mechanisms of the various liver disorders described in SAVI patients are needed, inflammatory liver manifestations may be amplified in the context of SAVI.