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Tocilizumab reduces the unmanageable inflammatory reaction of a patient with Aicardi-Goutières syndrome type 7 during treatment with ruxolitinib

BACKGROUND: Aicardi-Goutières syndrome (AGS) is a rare hereditary early-onset encephalopathy characterized by upregulation of the type I interferon pathway, poorly responsive to conventional immunosuppression. CASE PRESENTATION: We describe a 7-year-old Chinese boy who developed symptoms at the age...

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Autores principales: Wang, Wei, Peng, Siming, Gao, Sihao, Quan, Meiying, Gou, Lijuan, Wang, Changyan, Sun, Zhixing, Li, Zhuo, Lian, Dongmei, Song, Hongmei
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10571391/
https://www.ncbi.nlm.nih.gov/pubmed/37828538
http://dx.doi.org/10.1186/s12969-023-00899-4
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author Wang, Wei
Wang, Wei
Peng, Siming
Gao, Sihao
Quan, Meiying
Gou, Lijuan
Wang, Changyan
Sun, Zhixing
Li, Zhuo
Lian, Dongmei
Song, Hongmei
author_facet Wang, Wei
Wang, Wei
Peng, Siming
Gao, Sihao
Quan, Meiying
Gou, Lijuan
Wang, Changyan
Sun, Zhixing
Li, Zhuo
Lian, Dongmei
Song, Hongmei
author_sort Wang, Wei
collection PubMed
description BACKGROUND: Aicardi-Goutières syndrome (AGS) is a rare hereditary early-onset encephalopathy characterized by upregulation of the type I interferon pathway, poorly responsive to conventional immunosuppression. CASE PRESENTATION: We describe a 7-year-old Chinese boy who developed symptoms at the age of 6 months. He presented with a chilblain-like rash, leukopenia, neutropenia, elevated liver enzymesgrowth retardation, microcephaly, elevated acute phase reactants, intracranial calcification and leukodystrophy. At the age of 3 years old, whole-exome sequencing confirmed a de novo heterozygous gain-of-function mutation, c.1016 C > A (p.Ala339Asp), in the IFIH1 gene, and he was diagnosed with AGS7. He was treated with ruxolitinib accompanied by steroids and thalidomide for about four years. The rash, hematological manifestations, and the liver function were all improved, but the erythrocyte sedimentation rate remained consistently elevated until the addition of tocilizumab, a monoclonal antibody against interleukin 6. CONCLUSIONS: Ruxolitinib was not successful in suppressing the inflammatory process, and tocilizumab produced highly encouraging results in reducing the inflammatory reaction of AGS. The study makes a significant contribution to the literature because we may found a potential alternative therapeutic option for AGS.
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spelling pubmed-105713912023-10-14 Tocilizumab reduces the unmanageable inflammatory reaction of a patient with Aicardi-Goutières syndrome type 7 during treatment with ruxolitinib Wang, Wei Wang, Wei Peng, Siming Gao, Sihao Quan, Meiying Gou, Lijuan Wang, Changyan Sun, Zhixing Li, Zhuo Lian, Dongmei Song, Hongmei Pediatr Rheumatol Online J Case Report BACKGROUND: Aicardi-Goutières syndrome (AGS) is a rare hereditary early-onset encephalopathy characterized by upregulation of the type I interferon pathway, poorly responsive to conventional immunosuppression. CASE PRESENTATION: We describe a 7-year-old Chinese boy who developed symptoms at the age of 6 months. He presented with a chilblain-like rash, leukopenia, neutropenia, elevated liver enzymesgrowth retardation, microcephaly, elevated acute phase reactants, intracranial calcification and leukodystrophy. At the age of 3 years old, whole-exome sequencing confirmed a de novo heterozygous gain-of-function mutation, c.1016 C > A (p.Ala339Asp), in the IFIH1 gene, and he was diagnosed with AGS7. He was treated with ruxolitinib accompanied by steroids and thalidomide for about four years. The rash, hematological manifestations, and the liver function were all improved, but the erythrocyte sedimentation rate remained consistently elevated until the addition of tocilizumab, a monoclonal antibody against interleukin 6. CONCLUSIONS: Ruxolitinib was not successful in suppressing the inflammatory process, and tocilizumab produced highly encouraging results in reducing the inflammatory reaction of AGS. The study makes a significant contribution to the literature because we may found a potential alternative therapeutic option for AGS. BioMed Central 2023-10-12 /pmc/articles/PMC10571391/ /pubmed/37828538 http://dx.doi.org/10.1186/s12969-023-00899-4 Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
spellingShingle Case Report
Wang, Wei
Wang, Wei
Peng, Siming
Gao, Sihao
Quan, Meiying
Gou, Lijuan
Wang, Changyan
Sun, Zhixing
Li, Zhuo
Lian, Dongmei
Song, Hongmei
Tocilizumab reduces the unmanageable inflammatory reaction of a patient with Aicardi-Goutières syndrome type 7 during treatment with ruxolitinib
title Tocilizumab reduces the unmanageable inflammatory reaction of a patient with Aicardi-Goutières syndrome type 7 during treatment with ruxolitinib
title_full Tocilizumab reduces the unmanageable inflammatory reaction of a patient with Aicardi-Goutières syndrome type 7 during treatment with ruxolitinib
title_fullStr Tocilizumab reduces the unmanageable inflammatory reaction of a patient with Aicardi-Goutières syndrome type 7 during treatment with ruxolitinib
title_full_unstemmed Tocilizumab reduces the unmanageable inflammatory reaction of a patient with Aicardi-Goutières syndrome type 7 during treatment with ruxolitinib
title_short Tocilizumab reduces the unmanageable inflammatory reaction of a patient with Aicardi-Goutières syndrome type 7 during treatment with ruxolitinib
title_sort tocilizumab reduces the unmanageable inflammatory reaction of a patient with aicardi-goutières syndrome type 7 during treatment with ruxolitinib
topic Case Report
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10571391/
https://www.ncbi.nlm.nih.gov/pubmed/37828538
http://dx.doi.org/10.1186/s12969-023-00899-4
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