Severe chronic non-bacterial osteomyelitis in combination with total MPO deficiency and responsiveness to TNFα inhibition
Journal article, 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 Three years after treatment initiation adalimumab was withdrawn, resulting in rapid symptom recurrence.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

University of Gothenburg

Karin Christenson

University of Gothenburg

Per Wekell

University of Gothenburg

NU Hospital Group

Sahlgrenska University Hospital

Halla Björnsdottir

University of Gothenburg

Agnes Dahlstrand Rudin

University of Gothenburg

Felix P. Sanchez Klose

University of Gothenburg

Tilmann Kallinich

Charité University Medicine Berlin

Amanda Welin

Linköping University

University of Gothenburg

Lena I. Björkman

University of Gothenburg

Sahlgrenska University Hospital

Johan Bylund

University of Gothenburg

Anna Karlsson-Bengtsson

University of Gothenburg

Chalmers, Life Sciences

Stefan Berg

University of Gothenburg

Sahlgrenska University Hospital

Frontiers in Immunology

1664-3224 (eISSN)

Vol. 14 1233101

The glycome of emergency neutrophils and implications in sepsis

Swedish Research Council (VR) (2018-03077), 2019-01-01 -- 2024-12-31.

Subject Categories

Rheumatology and Autoimmunity





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