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Severe chronic non-bacterial osteomyelitis in combination with total MPO deficiency and responsiveness to TNFα inhibition
We describe a female patient suffering from severe chronic non-bacterial osteomyelitis (CNO) with systemic inflammation and advanced malnutrition and complete deficiency of myeloperoxidase (MPO). CNO is a rare autoinflammatory bone disorder associated with dysregulation of the innate immune system....
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10637399/ https://www.ncbi.nlm.nih.gov/pubmed/37954595 http://dx.doi.org/10.3389/fimmu.2023.1233101 |
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author | Sundqvist, Martina Christenson, Karin Wekell, Per Björnsdottir, Halla Dahlstrand Rudin, Agnes Sanchez Klose, Felix P. Kallinich, Tilmann Welin, Amanda Björkman, Lena Bylund, Johan Karlsson-Bengtsson, Anna Berg, Stefan |
author_facet | Sundqvist, Martina Christenson, Karin Wekell, Per Björnsdottir, Halla Dahlstrand Rudin, Agnes Sanchez Klose, Felix P. Kallinich, Tilmann Welin, Amanda Björkman, Lena Bylund, Johan Karlsson-Bengtsson, Anna Berg, Stefan |
author_sort | Sundqvist, Martina |
collection | PubMed |
description | We describe a female patient suffering from severe chronic non-bacterial osteomyelitis (CNO) with systemic inflammation and advanced malnutrition and complete deficiency of myeloperoxidase (MPO). CNO is a rare autoinflammatory bone disorder associated with dysregulation of the innate immune system. MPO deficiency is a genetic disorder with partial or complete absence of the phagocyte peroxidase MPO. MPO deficiency has no established clinical phenotype but reports indicate increased susceptibility to infection and chronic inflammation. The patient’s symptoms began at 10 years of age with pain in the thighs, systemic inflammation and malnutrition. She was diagnosed with CNO at 14 years of age. Treatment with nonsteroidal anti-inflammatory drugs, corticosteroids, bisphosphonates or IL1-receptor antagonists (anakinra) did not relieve the symptoms. However, the patient responded instantly and recovered from her clinical symptoms when treated with TNFα blockade (adalimumab). Three years after treatment initiation adalimumab was withdrawn, resulting in rapid symptom recurrence. When reintroducing adalimumab, the patient promptly responded and went into remission. In addition to clinical and laboratory profiles, neutrophil functions (reactive oxygen species, ROS; neutrophil extracellular traps, NETs; degranulation; apoptosis; elastase activity) were investigated both in a highly inflammatory state (without treatment) and in remission (on treatment). At diagnosis, neither IL1β, IL6, nor TNFα was significantly elevated in serum, but since TNFα blockade terminated the inflammatory symptoms, the disease was likely TNFα-driven. All neutrophil parameters were normal both during treatment and treatment withdrawal, except for MPO-dependent intracellular ROS- and NET formation. The role of total MPO deficiency for disease etiology and severity is discussed. |
format | Online Article Text |
id | pubmed-10637399 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-106373992023-11-11 Severe chronic non-bacterial osteomyelitis in combination with total MPO deficiency and responsiveness to TNFα inhibition Sundqvist, Martina Christenson, Karin Wekell, Per Björnsdottir, Halla Dahlstrand Rudin, Agnes Sanchez Klose, Felix P. Kallinich, Tilmann Welin, Amanda Björkman, Lena Bylund, Johan Karlsson-Bengtsson, Anna Berg, Stefan Front Immunol Immunology We describe a female patient suffering from severe chronic non-bacterial osteomyelitis (CNO) with systemic inflammation and advanced malnutrition and complete deficiency of myeloperoxidase (MPO). CNO is a rare autoinflammatory bone disorder associated with dysregulation of the innate immune system. MPO deficiency is a genetic disorder with partial or complete absence of the phagocyte peroxidase MPO. MPO deficiency has no established clinical phenotype but reports indicate increased susceptibility to infection and chronic inflammation. The patient’s symptoms began at 10 years of age with pain in the thighs, systemic inflammation and malnutrition. She was diagnosed with CNO at 14 years of age. Treatment with nonsteroidal anti-inflammatory drugs, corticosteroids, bisphosphonates or IL1-receptor antagonists (anakinra) did not relieve the symptoms. However, the patient responded instantly and recovered from her clinical symptoms when treated with TNFα blockade (adalimumab). Three years after treatment initiation adalimumab was withdrawn, resulting in rapid symptom recurrence. When reintroducing adalimumab, the patient promptly responded and went into remission. In addition to clinical and laboratory profiles, neutrophil functions (reactive oxygen species, ROS; neutrophil extracellular traps, NETs; degranulation; apoptosis; elastase activity) were investigated both in a highly inflammatory state (without treatment) and in remission (on treatment). At diagnosis, neither IL1β, IL6, nor TNFα was significantly elevated in serum, but since TNFα blockade terminated the inflammatory symptoms, the disease was likely TNFα-driven. All neutrophil parameters were normal both during treatment and treatment withdrawal, except for MPO-dependent intracellular ROS- and NET formation. The role of total MPO deficiency for disease etiology and severity is discussed. Frontiers Media S.A. 2023-10-26 /pmc/articles/PMC10637399/ /pubmed/37954595 http://dx.doi.org/10.3389/fimmu.2023.1233101 Text en Copyright © 2023 Sundqvist, Christenson, Wekell, Björnsdottir, Dahlstrand Rudin, Sanchez Klose, Kallinich, Welin, Björkman, Bylund, Karlsson-Bengtsson and Berg https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Immunology Sundqvist, Martina Christenson, Karin Wekell, Per Björnsdottir, Halla Dahlstrand Rudin, Agnes Sanchez Klose, Felix P. Kallinich, Tilmann Welin, Amanda Björkman, Lena Bylund, Johan Karlsson-Bengtsson, Anna Berg, Stefan Severe chronic non-bacterial osteomyelitis in combination with total MPO deficiency and responsiveness to TNFα inhibition |
title | Severe chronic non-bacterial osteomyelitis in combination with total MPO deficiency and responsiveness to TNFα inhibition |
title_full | Severe chronic non-bacterial osteomyelitis in combination with total MPO deficiency and responsiveness to TNFα inhibition |
title_fullStr | Severe chronic non-bacterial osteomyelitis in combination with total MPO deficiency and responsiveness to TNFα inhibition |
title_full_unstemmed | Severe chronic non-bacterial osteomyelitis in combination with total MPO deficiency and responsiveness to TNFα inhibition |
title_short | Severe chronic non-bacterial osteomyelitis in combination with total MPO deficiency and responsiveness to TNFα inhibition |
title_sort | severe chronic non-bacterial osteomyelitis in combination with total mpo deficiency and responsiveness to tnfα inhibition |
topic | Immunology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10637399/ https://www.ncbi.nlm.nih.gov/pubmed/37954595 http://dx.doi.org/10.3389/fimmu.2023.1233101 |
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