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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....

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Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2023
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.
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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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