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A novel TNFRSF1A mutation associated with TNF-receptor-associated periodic syndrome and its metabolic signature
OBJECTIVE: We describe a family with a novel mutation in the TNF Receptor Superfamily Member 1A (TNFRSF1A) gene causing TNF receptor–associated periodic syndrome (TRAPS) with renal AA amyloidosis. METHODS: Case series of affected family members. We further investigated the plasma metabolome of these...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Oxford University Press
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10547530/ https://www.ncbi.nlm.nih.gov/pubmed/36752501 http://dx.doi.org/10.1093/rheumatology/kead068 |
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author | Steiner, Joachim D Annibal, Andrea Laboy, Raymond Braumann, Marie Göbel, Heike Laasch, Valentin Müller, Roman-Ulrich Späth, Martin R Antebi, Adam Kubacki, Torsten |
author_facet | Steiner, Joachim D Annibal, Andrea Laboy, Raymond Braumann, Marie Göbel, Heike Laasch, Valentin Müller, Roman-Ulrich Späth, Martin R Antebi, Adam Kubacki, Torsten |
author_sort | Steiner, Joachim D |
collection | PubMed |
description | OBJECTIVE: We describe a family with a novel mutation in the TNF Receptor Superfamily Member 1A (TNFRSF1A) gene causing TNF receptor–associated periodic syndrome (TRAPS) with renal AA amyloidosis. METHODS: Case series of affected family members. We further investigated the plasma metabolome of these patients in comparison with healthy controls using mass spectrometry. RESULTS: In all symptomatic family members, we detected the previously undescribed variant c.332A>G (p.Q111R) in the TNFRSF1A gene. Canakinumab proved an effective treatment option leading to remission in all treated patients. One patient with suspected renal amyloidosis showed near normalization of proteinuria under treatment. Analysis of the metabolome revealed 31 metabolic compounds to be upregulated and 35 compounds to be downregulated compared with healthy controls. The most dysregulated metabolites belonged to pathways identified as arginine biosynthesis, phenylalanine, tyrosine and tryptophan biosynthesis, and cysteine and methionine metabolism. Interestingly, the metabolic changes observed in all three TRAPS patients seemed independent of treatment with canakinumab and subsequent remission. CONCLUSION: We present a novel mutation in the TNFRSF1A gene associated with amyloidosis. Canakinumab is an effective treatment for individuals with this new likely pathogenic variant. Alterations in the metabolome were most prominent in the pathways related to arginine biosynthesis, tryptophan metabolism, and metabolism of cysteine and methionine, and seemed to be unaffected by treatment with canakinumab. Further investigation is needed to determine the role of these metabolomic changes in the pathophysiology of TRAPS. |
format | Online Article Text |
id | pubmed-10547530 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Oxford University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-105475302023-10-04 A novel TNFRSF1A mutation associated with TNF-receptor-associated periodic syndrome and its metabolic signature Steiner, Joachim D Annibal, Andrea Laboy, Raymond Braumann, Marie Göbel, Heike Laasch, Valentin Müller, Roman-Ulrich Späth, Martin R Antebi, Adam Kubacki, Torsten Rheumatology (Oxford) Basic Science OBJECTIVE: We describe a family with a novel mutation in the TNF Receptor Superfamily Member 1A (TNFRSF1A) gene causing TNF receptor–associated periodic syndrome (TRAPS) with renal AA amyloidosis. METHODS: Case series of affected family members. We further investigated the plasma metabolome of these patients in comparison with healthy controls using mass spectrometry. RESULTS: In all symptomatic family members, we detected the previously undescribed variant c.332A>G (p.Q111R) in the TNFRSF1A gene. Canakinumab proved an effective treatment option leading to remission in all treated patients. One patient with suspected renal amyloidosis showed near normalization of proteinuria under treatment. Analysis of the metabolome revealed 31 metabolic compounds to be upregulated and 35 compounds to be downregulated compared with healthy controls. The most dysregulated metabolites belonged to pathways identified as arginine biosynthesis, phenylalanine, tyrosine and tryptophan biosynthesis, and cysteine and methionine metabolism. Interestingly, the metabolic changes observed in all three TRAPS patients seemed independent of treatment with canakinumab and subsequent remission. CONCLUSION: We present a novel mutation in the TNFRSF1A gene associated with amyloidosis. Canakinumab is an effective treatment for individuals with this new likely pathogenic variant. Alterations in the metabolome were most prominent in the pathways related to arginine biosynthesis, tryptophan metabolism, and metabolism of cysteine and methionine, and seemed to be unaffected by treatment with canakinumab. Further investigation is needed to determine the role of these metabolomic changes in the pathophysiology of TRAPS. Oxford University Press 2023-02-08 /pmc/articles/PMC10547530/ /pubmed/36752501 http://dx.doi.org/10.1093/rheumatology/kead068 Text en © The Author(s) 2023. Published by Oxford University Press on behalf of the British Society for Rheumatology. https://creativecommons.org/licenses/by-nc/4.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial License (https://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com |
spellingShingle | Basic Science Steiner, Joachim D Annibal, Andrea Laboy, Raymond Braumann, Marie Göbel, Heike Laasch, Valentin Müller, Roman-Ulrich Späth, Martin R Antebi, Adam Kubacki, Torsten A novel TNFRSF1A mutation associated with TNF-receptor-associated periodic syndrome and its metabolic signature |
title | A novel TNFRSF1A mutation associated with TNF-receptor-associated periodic syndrome and its metabolic signature |
title_full | A novel TNFRSF1A mutation associated with TNF-receptor-associated periodic syndrome and its metabolic signature |
title_fullStr | A novel TNFRSF1A mutation associated with TNF-receptor-associated periodic syndrome and its metabolic signature |
title_full_unstemmed | A novel TNFRSF1A mutation associated with TNF-receptor-associated periodic syndrome and its metabolic signature |
title_short | A novel TNFRSF1A mutation associated with TNF-receptor-associated periodic syndrome and its metabolic signature |
title_sort | novel tnfrsf1a mutation associated with tnf-receptor-associated periodic syndrome and its metabolic signature |
topic | Basic Science |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10547530/ https://www.ncbi.nlm.nih.gov/pubmed/36752501 http://dx.doi.org/10.1093/rheumatology/kead068 |
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