Efficacy of anti-IL-1 treatment in Majeed syndrome
- Troels Herlin1,
- Bente Fiirgaard2,
- Mette Bjerre3,
- Gitte Kerndrup4,
- Henrik Hasle1,
- Xinyu Bing5,
- Polly J Ferguson5
- 1Department of Pediatrics, Aarhus University Hospital, Aarhus, Denmark
- 2Department of Radiology, MR Research Centre, Aarhus University Hospital, Aarhus, Denmark
- 3Medical Research Lab, Aarhus University Hospital, Aarhus, Denmark
- 4Clinical Genetics Department, Vejle Hospital, Vejle, Denmark
- 5Department of Pediatrics, University of Iowa, Carver College of Medicine, Iowa City, Iowa, USA
- Correspondence to Dr Polly J Ferguson, Department of Pediatrics, University of Iowa, 200 Hawkins Drive, 4038 Boyd Tower, Iowa City, IA 52242, USA;
- Accepted 5 October 2012
- Published Online First 20 October 2012
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.