Elevation of soluble Fas and soluble Fas ligand in reactive macrophage activation syndromes

Derailed T-cell activation can give rise to life-threatening macrophage act ivation, the final common pathway of the different forms of reactive macrop hage activation syndromes (rMAS). Besides inappropriate activation of the i mmune system, impaired termination of immune responses might be another mec hanism leading to rMAS, The Fas (CD95)/Fas ligand (CD95 ligand) system func tions 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 potenti al parameters of impaired immune termination. Hence, sFas and sFasL were an alyzed in sera of rMAS patients. We show that soluble Fas/CD95 (sFas) is el evated >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, rang e 0.16-1.28; controls all below the limit of detection of 0.1). In addition , both parameters decrease during convalescence, reflecting clinical evolut ion. In conclusion, sFas seems to be consistently elevated during acute rMA S. sFasL is detected only in a subgroup of our adult rMAS patients extendin g the recent finding of sFasL elevation in a majority of children with macr ophage activation syndromes (Hasegawa et al, Blood 1998;91 (8):2793-2799). By interfering with AICD, sFas and sFasL might contribute to the pathogenes is of at least a subset of rMAS. Am. J. Hematol. 64:116-119, 2000, (C) 2000 Wiley-Liss, Inc.