Severe chronic non-bacterial osteomyelitis in combination with total MPO deficiency and responsiveness to TNFα inhibition
Artikel i vetenskaplig tidskrift, 2023

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 Three years after treatment initiation adalimumab was withdrawn, resulting in rapid symptom recurrence.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.









Martina Sundqvist

Göteborgs universitet

Karin Christenson

Göteborgs universitet

Per Wekell

Sahlgrenska universitetssjukhuset

Göteborgs universitet


Halla Björnsdottir

Göteborgs universitet

Agnes Dahlstrand Rudin

Göteborgs universitet

Felix P. Sanchez Klose

Göteborgs universitet

Tilmann Kallinich

Charité Universitätsmedizin Berlin

Amanda Welin

Göteborgs universitet

Linköpings universitet

Lena I. Björkman

Sahlgrenska universitetssjukhuset

Göteborgs universitet

Johan Bylund

Göteborgs universitet

Anna Karlsson-Bengtsson

Chalmers, Life sciences

Göteborgs universitet

Stefan Berg

Göteborgs universitet

Sahlgrenska universitetssjukhuset

Frontiers in Immunology

1664-3224 (eISSN)

Vol. 14 1233101

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