title: Autoinflammatory bone disorders: update on immunologic abnormalities and clues about possible triggers.
abstract: OBJECTIVE
  To provide an update on the genetics and immunologic basis of autoinflammatory bone disorders including chronic recurrent multifocal osteomyelitis including the monogenic forms of the disease.
  
  
  RESULTS
  Ongoing research in murine, canine and human models of sterile bone inflammation has solidified the hypothesis that sterile bone inflammation can be genetically driven. Mutations in Pstpip2, LPIN2 and IL1RN have been identified in monogenic autoinflammatory bone disorders that have allowed more detailed dissection of the immunologic defects that can produce sterile osteomyelitis. Recent studies in murine chronic multifocal osteomyelitis, deficiency of the interleukin-1 receptor antagonist (DIRA), Majeed syndrome and SAPHO syndrome reveal abnormalities in innate immune system function. IL-1 pathway dysregulation is present in several of these disorders and blocking IL-1 therapeutically has resulted in control of disease in DIRA, Majeed syndrome and in some cases of SAPHO and CRMO. Basic research demonstrates the importance of the innate immune system in disease pathogenesis and offers clues about potential disease triggers.
  
  
  CONCLUSIONS
  Research and clinical data produced over the last several years support the important role of innate immunity in sterile osteomyelitis. Based on what has been learned in the monogenic autoinflammatory bone disorders, IL-1 is emerging as an important pathway in the development of sterile bone inflammation.
authors.affiliation: Divisions of Rheumatology in Internal Medicine and Pediatrics, University of Iowa, Iowa City, Iowa 52240, USA.
authors.forename: Manisha
authors.initials: M
authors.lastname: Sharma
authors.forename: Polly J
authors.initials: PJ
authors.lastname: Ferguson
mesh_terms: D020083:Acquired Hyperostosis Syndrome / Q000382:microbiology; D000742:Anemia, Dyserythropoietic, Congenital / Q000188:drug therapy / Q000209:etiology / Q000235:genetics / Q000276:immunology; D000818:Animals; D002908:Chronic Disease; D004195:Disease Models, Animal; D004285:Dogs; D016908:Gram-Positive Bacterial Infections / Q000150:complications; D056660:Hereditary Autoinflammatory Diseases / Q000235:genetics / Q000276:immunology*; D006801:Humans; D007113:Immunity, Innate; D007153:Immunologic Deficiency Syndromes; D007375:Interleukin-1 / Q000037:antagonists & inhibitors; D051379:Mice; D010019:Osteomyelitis / Q000188:drug therapy / Q000209:etiology / Q000235:genetics / Q000276:immunology*; D011425:Propionibacterium acnes; D012008:Recurrence; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors
chemical_list: D007375:Interleukin-1; D014409:Tumor Necrosis Factor-alpha
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