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

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Abstract

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 develo** 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.

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Acknowledgment

We are grateful to the patient and family who participated in this study. This work was supported in part by a Grant in Aid for Scientific Research (C) (Grant Number 18 K07807) and the Japan Agency for Medical Research and Development (Grant/Award Number 19kk0205014h0004).

Funding

This work was supported in part by a Grant in Aid for Scientific Research (C) (Grant Number 18 K07807) and the Japan Agency for Medical Research and Development (Grant/Award Number 19kk0205014h0004).

Author information

Authors and Affiliations

  1. Division of Immunology, National Center for Child Health and Development, 2-10-1 Okura, Setagaya-ku, Tokyo, 157-8535, Japan

    Takashi Ishikawa, Eiichiro Tamura, Toru Uchiyama, Masafumi Onodera & Toshinao Kawai

  2. Department of Pediatrics, The Jikei University School of Medicine, 3-19-18 Nishishinbashi, Minato-ku, Tokyo, 105-8471, Japan

    Takashi Ishikawa, Eiichiro Tamura & Toshinao Kawai

  3. Center for Organ Transplantation, National Center for Child Health and Development, 2-10-1 Okura, Setagaya-ku, Tokyo, 157-8535, Japan

    Mureo Kasahara & Hajime Uchida

  4. Division of Pulmonology, National Center for Child Health and Development, 2-10-1 Okura, Setagaya-ku, Tokyo, 157-8535, Japan

    Masataka Higuchi & Hisato Kobayashi

  5. Department of Pediatrics, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo, 160-8582, Japan

    Hisato Kobayashi

  6. Division of Gastroenterology, National Center for Child Health and Development, 2-10-1 Okura, Setagaya-ku, Tokyo, 157-8535, Japan

    Hirotaka Shimizu

  7. Division of Infectious Diseases, National Center for Child Health and Development, 2-10-1 Okura, Setagaya-ku, Tokyo, 157-8535, Japan

    Eiki Ogawa

  8. Division of Palliative Medicine, National Center for Child Health and Development, 2-10-1 Okura, Setagaya-ku, Tokyo, 157-8535, Japan

    Nobuyuki Yotani

  9. Department of Pathology, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo, 160-8582, Japan

    Rie Irie

  10. Division of Medical Genetics, National Center for Child Health and Development, 2-10-1 Okura, Setagaya-ku, Tokyo, 157-8535, Japan

    Rika Kosaki

  11. Center for Medical Genetics, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo, 160-8582, Japan

    Kenjiro Kosaki

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  1. Takashi Ishikawa
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Contributions

T.I., E.T., M.K., H.U., M.H., H.K., H.S., E.O., N.Y., and R.I. managed patients and designed research. T.U., M.O., and T.K. performed research and analyzed data. R.K. and K.K. performed genetic analysis. T.I., H.U., M.H., R.I., and T.K. contributed to the writing of the manuscript. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Toshinao Kawai.

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The authors declare that they have no conflicts of interest.

Ethics Approval

This study was approved by the Ethics Committee of the National Center for Child Health and Development (reference number 378).

Consent to Participate

All procedures and experiments were performed after receiving informed consent from the patient’s parents.

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The consent for publication of the clinical details and/or clinical images was obtained from the patient’s parents.

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Ishikawa, T., Tamura, E., Kasahara, M. et al. Severe Liver Disorder Following Liver Transplantation in STING-Associated Vasculopathy with Onset in Infancy. J Clin Immunol 41, 967–974 (2021). https://doi.org/10.1007/s10875-021-00977-w

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