title: Elevation of soluble Fas and soluble Fas ligand in reactive macrophage activation syndromes.
abstract: Derailed T-cell activation can give rise to life-threatening macrophage activation, the final common pathway of the different forms of reactive macrophage activation syndromes (rMAS). Besides inappropriate activation of the immune system, impaired termination of immune responses might be another mechanism leading to rMAS. The Fas (CD95)/Fas ligand (CD95 ligand) system functions in turning off immune responses by executing activation-induced cell death (AICD). Soluble Fas (sFas) and Fas ligand (sFasL) can interfere with their corresponding membrane-bound counterparts, qualifying them as potential parameters of impaired immune termination. Hence, sFas and sFasL were analyzed in sera of rMAS patients. We show that soluble Fas/CD95 (sFas) is elevated >2 SD over the mean of controls in all 8 rMAS episodes studied (mean 12.08 +/- 6.12 ng/mL, range 3.7-20.2; controls 2.46 +/- 0.49, range 1.5-2.9). sFasL was detected during five rMAS episodes (0.70 +/- 0.49 ng/mL, range 0.16-1.28; controls all below the limit of detection of 0.1). In addition, both parameters decrease during convalescence, reflecting clinical evolution. In conclusion, sFas seems to be consistently elevated during acute rMAS. sFasL is detected only in a subgroup of our adult rMAS patients extending the recent finding of sFasL elevation in a majority of children with macrophage activation syndromes (Hasegawa et al. Blood 1998;91(8):2793-2799). By interfering with AICD, sFas and sFasL might contribute to the pathogenesis of at least a subset of rMAS.
authors.affiliation: Department of Internal Medicine, Zieglerspital, Bern, Switzerland.
authors.forename: U
authors.initials: U
authors.lastname: Emmenegger
authors.forename: R
authors.initials: R
authors.lastname: Zehnder
authors.forename: U
authors.initials: U
authors.lastname: Frey
authors.forename: A
authors.initials: A
authors.lastname: Reimers
authors.forename: P J
authors.initials: PJ
authors.lastname: Spaeth
authors.forename: K A
authors.initials: KA
authors.lastname: Neftel
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D053222:Fas Ligand Protein; D005260:Female; D015616:Histiocytosis, Non-Langerhans-Cell / Q000097:blood / Q000503:physiopathology*; D006801:Humans; D008262:Macrophage Activation; D008297:Male; D008562:Membrane Glycoproteins / Q000097:blood*; D008875:Middle Aged; D012995:Solubility; D019014:fas Receptor / Q000097:blood*
chemical_list: C505661:FASLG protein, human; D053222:Fas Ligand Protein; D008562:Membrane Glycoproteins; D019014:fas Receptor