Efficacy of anti-IL-1 treatment in Majeed syndrome.

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.

• Authors: Troels Herlin, Bente Fiirgaard, Mette Bjerre, Gitte Kerndrup, Henrik Hasle, Xinyu Bing, Polly J Ferguson
• Journal: Annals of the rheumatic diseases (Ann Rheum Dis) Vol. 72 Issue 3 Pg. 410-3 (Mar 2013) ISSN: 1468-2060 [Electronic] England
• PMID: 23087183 (Publication Type: Case Reports, Journal Article, Research Support, N.I.H., Extramural)

Chemical References

• Antibodies, Monoclonal
• Antibodies, Monoclonal, Humanized
• Antirheumatic Agents
• Cytokines
• Interleukin 1 Receptor Antagonist Protein
• Interleukin-1
• LPIN2 protein, human
• Nuclear Proteins
• canakinumab

Topics

• Anemia, Dyserythropoietic, Congenital (drug therapy, genetics, immunology)
• Antibodies, Monoclonal (therapeutic use)
• Antibodies, Monoclonal, Humanized
• Antirheumatic Agents (therapeutic use)
• Base Sequence
• Child, Preschool
• Cytokines (analysis, blood)
• Humans
• Immunologic Deficiency Syndromes
• Infant
• Interleukin 1 Receptor Antagonist Protein (therapeutic use)
• Interleukin-1 (antagonists & inhibitors)
• Male
• Nuclear Proteins (genetics)
• Osteomyelitis (drug therapy, genetics, immunology)
• Siblings