title: Reaching the threshold: a multilayer pathogenesis of macrophage activation syndrome.
abstract: Macrophage activation syndrome (MAS) is a potentially fatal complication of rheumatic diseases. The condition is considered part of secondary hemophagocytic lymphohistiocytoses (HLH). There are similarities in genetic background, pathogenesis, and clinical and laboratory features with primary HLH (p-HLH). We describe findings in mouse models of secondary HLH, comparing them with models of p-HLH and the cellular and molecular mechanisms involved, and relate them to recent findings in patients with secondary HLH. A multilayer model is presented in which background inflammation, infections, and genetics all contribute in different proportions and in several ways. Once the "threshold" has been reached, inflammatory cytokines are the final effectors, independent of the interplay between different upstream pathogenic factors.
authors.affiliation: Division of Rheumatology, IRCCS Ospedale Pediatrico Bambino Gesù, Rome, Italy. rafstrippoli@libero.it
authors.forename: Raffaele
authors.initials: R
authors.lastname: Strippoli
authors.forename: Ivan
authors.initials: I
authors.lastname: Caiello
authors.forename: Fabrizio
authors.initials: F
authors.lastname: De Benedetti
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D006801:Humans; D007249:Inflammation / Q000150:complications / Q000276:immunology / Q000503:physiopathology; D008262:Macrophage Activation; D055501:Macrophage Activation Syndrome / Q000209:etiology* / Q000276:immunology / Q000503:physiopathology; D051379:Mice; D012216:Rheumatic Diseases / Q000150:complications* / Q000276:immunology / Q000503:physiopathology
keywords: ETIOLOGY; HEMOPHAGOCYTIC LYMPHOHISTIOCYTOSES; JUVENILE IDIOPATHIC ARTHRITIS; MACROPHAGE ACTIVATION SYNDROME