title: Efficacy of anti-IL-1 treatment in Majeed syndrome.
abstract: 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.affiliation: Department of Pediatrics, Aarhus University Hospital, Aarhus, Denmark.
authors.forename: Troels
authors.initials: T
authors.lastname: Herlin
authors.forename: Bente
authors.initials: B
authors.lastname: Fiirgaard
authors.forename: Mette
authors.initials: M
authors.lastname: Bjerre
authors.forename: Gitte
authors.initials: G
authors.lastname: Kerndrup
authors.forename: Henrik
authors.initials: H
authors.lastname: Hasle
authors.forename: Xinyu
authors.initials: X
authors.lastname: Bing
authors.forename: Polly J
authors.initials: PJ
authors.lastname: Ferguson
mesh_terms: D000742:Anemia, Dyserythropoietic, Congenital / Q000188:drug therapy* / Q000235:genetics* / Q000276:immunology; D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D061067:Antibodies, Monoclonal, Humanized; D018501:Antirheumatic Agents / Q000627:therapeutic use*; D001483:Base Sequence; D002675:Child, Preschool; D016207:Cytokines / Q000032:analysis / Q000097:blood; D006801:Humans; D007153:Immunologic Deficiency Syndromes; D007223:Infant; D053590:Interleukin 1 Receptor Antagonist Protein / Q000627:therapeutic use; D007375:Interleukin-1 / Q000037:antagonists & inhibitors*; D008297:Male; D009687:Nuclear Proteins / Q000235:genetics*; D010019:Osteomyelitis / Q000188:drug therapy* / Q000235:genetics* / Q000276:immunology; D035781:Siblings
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D018501:Antirheumatic Agents; D016207:Cytokines; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1; C502575:LPIN2 protein, human; D009687:Nuclear Proteins; C541220:canakinumab