RT Journal Article
SR Electronic
T1 Reaching the Threshold: A Multilayer Pathogenesis of Macrophage Activation Syndrome
JF The Journal of Rheumatology
JO J Rheumatol
FD The Journal of Rheumatology
SP 761
OP 767
DO 10.3899/jrheum.121233
VO 40
IS 6
A1 Raffaele Strippoli
A1 Ivan Caiello
A1 Fabrizio De Benedetti
YR 2013
UL http://www.jrheum.org/content/40/6/761.abstract
AB 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.