Session Type: ACR Concurrent Abstract Session
Session Time: 2:30PM-4:00PM
Background/Purpose: Evidence in animals and humans points to a pivotal role of IFNγ in primary HLH. We have recently generated data in an animal model supporting a role for IFNγ also in MAS and reported high levels of IFNγ and of the IFNγ-related chemokines, CXCL9, CXCL10 in patients with MAS, during systemic JIA (sJIA) (1).
Methods: Circulating levels of sCD25, IL-18 and neopterin, as well as levels of IFNγ, CXCL9 and CXCL10 were measured by Luminex assay in 57 samples obtained, from 24 patients with active sJIA and in 37 samples from 20 patients with MAS at sampling at variable severity and treatments. We evaluated the correlation between serum levels of sCD25, IL-18 and neopterin, as well as levels of IFNγ of CXCL9 and CXCL10 with laboratory parameters of MAS severity in patients with active sJIA with or without MAS at sampling.
Results: Levels of IFNγ, CXCL9, CXCL10, sCD25, IL-18 and neopterin were significantly elevated in MAS compared to active sJIA without MAS at sampling (p-values <0.0001, except for IL-18 p=0.012). In patients with MAS, but not in patients with active sJIA without MAS at sampling, laboratory parameters of disease severity were significantly correlated with IFNγ, CXCL9, CXCL10, sCD25 and neopterin (Table1). No correlation with IL-18 was found (IL-18 levels were available only for a portion of the samples). Interestingly, during active sJIA without MAS at sampling, levels of CXCL9 (median 3889,IQR 965-7142), CXCL10 (764,323-1259) and IL-18 (4405,582-7122) were significantly higher in patients with a history of MAS compared to those of patients without a history of MAS (519,IQR 385-1168; 215,IQR 152-470; 439,312-824, respectively). Table 1.Correlation between cytokines and laboratory parameters in active MAS (N=37).
|p (r)||p (r)||p (r)||p (r)||p (r)||p (r)|
|White blood cells (x10^9/L)||0.033(-0.47)||0.013(-0.56)||>0.1(-0.32)||>0.1(-0.42)||>0.1(-0.40)||>0.1(0.04)|
|Triglycerids (mg/dL)||>0.1 (0.20)||>0.1 (0.23)||>0.1(0.13)||>0.1(0.29)||>0.1 (0.02)||>0.1 (0.17)|
|LDH (U/L)||0.005(0.64)||<0.0001(0.90)||<0.0001(0.94)||0.002(0.69)||>0.1 (-0.23)||0.0001 (0.85)|
|ALT (U/L)||0.012 (0.52)||0.0007 (0.68)||0.0005 (0.67)||0.008 (0.54)||>0.1 (0.38)||>0.1 (0.14)|
|Values are expressed as p value (r di Spearman).|
Conclusion: Levels of IFNγ, CXCL9, CXCL10, sCD25, and neopterin were higher during MAS and correlated with laboratory parameters of severity. IL-18 levels were not correlated with laboratory parameters of MAS severity and the observation that IL-18 levels are higher in patients with a history of MAS is consistent with the hypothesis that high levels of IL-18 may contribute to the predisposition to MAS in sJIA as also suggested by Shimizu et al (2). Elevation of sCD25 is consistent with the presence of T cell activation in MAS. Elevation of neopterin and CXCL9, both of which reflects IFNγ production, and their correlation with laboratory parameters, supports the pathogenic role of IFNγ in MAS. Given the fact that circulating CXCL9 levels appear to reflect tissue IFNγ production, presence of high CXCL9 in patients with a history of MAS, but without MAS at sampling, suggests subclinical activation of the IFNγ pathway in these patients. References. 1. Bracaglia c. et al. Ann Rheum Dis 2016 2. Shimizu M. et al. Clin immunol 2015
To cite this abstract in AMA style:Bracaglia C, Pires Marafon D, Caiello I, de Graaf K, Guilhot F, Ferlin W, Davì S, Schulert G, Ravelli A, Grom A, Nelson R, de Min C, De Benedetti F. IFN-Gamma (IFNγ), IFNγ-Induced Chemokines and Other Biomarkers in Macrophage Activation Syndrome (MAS) [abstract]. Arthritis Rheumatol. 2016; 68 (suppl 10). https://acrabstracts.org/abstract/ifn-gamma-ifn%ce%b3-ifn%ce%b3-induced-chemokines-and-other-biomarkers-in-macrophage-activation-syndrome-mas/. Accessed March 20, 2019.
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