title: Macrophage Activation Syndrome: different mechanisms leading to a one clinical syndrome.
abstract: BACKGROUND
  Macrophage activation syndrome (MAS) is a severe complication of rheumatic disease in childhood, particularly in systemic Juvenile Idiopathic Arthritis (sJIA). It is characterize by an uncontrolled activation and proliferation of T lymphocytes and macrophages.
  
  
  METHODS
  MAS is currently classified among the secondary or acquired forms of haemophagocytic lymphohistiocytosis (sHLH). The reason is that MAS shares clinical and laboratory features with primary genetic HLH (pHLH). In this context is conceivable that some of the pathogenic mechanisms of pHLH may be involved in other forms of HLH. Heterozygosity for mutations of genes involved in pHLH may lead to a cytotoxic defect and to a development of clinical overt disease. But other different contributors might be involved to the development of MAS such as infections or underlying inflammation. In MAS, the inflammatory status of the patient is a major contributor of the disease. Indeed, the majority of the MAS episodes occurs during active disease phases or at disease onset. In addition, recent evidence in animals and humans suggest that genetics may also play a major role in contributing to hyperinflammation and particularly to macrophages hyper-responses.
  
  
  CONCLUSIONS
  We hypothesize that HLH may be one unique clinical syndrome, to whose generation different mechanisms may contribute, and maintained by one final effector mechanism.
authors.affiliation: Division of Rheumatology, Ospedale Pediatrico Bambino Gesù IRCCS, Piazza S. Onofrio 4, 00165, Rome, Italy. claudia.bracaglia@opbg.net.
authors.forename: Claudia
authors.identifier: http://orcid.org/0000-0002-9834-9619
authors.initials: C
authors.lastname: Bracaglia
authors.affiliation: Division of Rheumatology, Ospedale Pediatrico Bambino Gesù IRCCS, Piazza S. Onofrio 4, 00165, Rome, Italy.
authors.forename: Giusi
authors.initials: G
authors.lastname: Prencipe
authors.affiliation: Division of Rheumatology, Ospedale Pediatrico Bambino Gesù IRCCS, Piazza S. Onofrio 4, 00165, Rome, Italy.
authors.forename: Fabrizio
authors.initials: F
authors.lastname: De Benedetti
mesh_terms: D000818:Animals; D018501:Antirheumatic Agents / Q000627:therapeutic use; D001171:Arthritis, Juvenile / Q000503:physiopathology; D018925:Chemokines / Q000096:biosynthesis; D016207:Cytokines / Q000096:biosynthesis; D004195:Disease Models, Animal; D020022:Genetic Predisposition to Disease / Q000235:genetics; D006801:Humans; D007371:Interferon-gamma / Q000502:physiology; D015850:Interleukin-6 / Q000494:pharmacology; D007694:Killer Cells, Natural / Q000502:physiology; D008213:Lymphocyte Activation / Q000502:physiology; D008262:Macrophage Activation / Q000502:physiology; D055501:Macrophage Activation Syndrome / Q000145:classification / Q000188:drug therapy / Q000209:etiology*; D018345:Mice, Knockout; D008822:Mice, Transgenic; D009154:Mutation / Q000502:physiology
chemical_list: D018501:Antirheumatic Agents; D018925:Chemokines; D016207:Cytokines; D015850:Interleukin-6; D007371:Interferon-gamma
keywords: Haemophagocytic lymphohistiocytosis; IFNγ; IL-18; IL-6; Inflammasome; Macrophage activation syndrome; Natural killer