Journal article
Efficacy of anti-IL-1 treatment in Majeed syndrome
Annals of the rheumatic diseases, Vol.72(3), pp.410-413
03/2013
DOI: 10.1136/annrheumdis-2012-201818
PMCID: PMC3660147
PMID: 23087183
Abstract
Background and objective Majeed syndrome is an autosomal recessive disorder characterised by the triad of chronic recurrent multifocal osteomyelitis, congenital dyserythropoietic anaemia and a neutrophilic dermatosis that is caused by mutations in LPIN2. Long-term outcome is poor. This is the first report detailing the treatment of Majeed syndrome with biological agents and demonstrates clinical improvement with IL-1blockade. Methods We describe the clinical presentation, genetic analysis, cytokine profiles and response to biological therapy in two brothers with Majeed syndrome. Results Both boys were homozygous for a novel 2-base pair deletion in LPIN2 (c.1312_1313delCT; p.Leu438fs+16X), confirming the diagnosis. Their bone disease and anaemia were refractory to treatment with corticosteroids. Both siblings had elevated proinflammatory cytokines in their serum, including tumour necrosis factor α (TNF-α), however a trial of the TNF inhibitor etanercept resulted in no improvement. IL-1 inhibition with either a recombinant IL-1 receptor antagonist (anakinra) or an anti-IL-1β antibody (canakinumab) resulted in dramatic clinical and laboratory improvement. Conclusions The differential response to treatment with TNF-α or IL-1 blocking agents sheds light into disease pathogenesis; it supports the hypothesis that Majeed syndrome is an IL-1β dependent autoinflammatory disorder, and further underscores the importance of IL-1 in sterile bone inflammation.
Details
- Title: Subtitle
- Efficacy of anti-IL-1 treatment in Majeed syndrome
- Creators
- Troels Herlin - Department of Pediatrics, Aarhus University Hospital, Aarhus, DenmarkBente Fiirgaard - Department of Radiology, MR Research Centre, Aarhus University Hospital, Aarhus, DenmarkMette Bjerre - Medical Research Lab, Aarhus University Hospital, Aarhus, DenmarkGitte Kerndrup - Clinical Genetics Department, Vejle Hospital, Vejle, DenmarkHenrik Hasle - Department of Pediatrics, Aarhus University Hospital, Aarhus, DenmarkXinyu Bing - Department of Pediatrics, University of Iowa, Carver College of Medicine, Iowa City, Iowa, USAPolly J Ferguson - Department of Pediatrics, University of Iowa, Carver College of Medicine, Iowa City, Iowa, USA
- Resource Type
- Journal article
- Publication Details
- Annals of the rheumatic diseases, Vol.72(3), pp.410-413
- DOI
- 10.1136/annrheumdis-2012-201818
- PMID
- 23087183
- PMCID
- PMC3660147
- ISSN
- 0003-4967
- eISSN
- 1468-2060
- Language
- English
- Date published
- 03/2013
- Academic Unit
- Critical Care; Stead Family Department of Pediatrics; Iowa Neuroscience Institute; Rheumatology, Allergy, and Immunology
- Record Identifier
- 9984065740402771
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