To compare the accuracy of serum biomarkers for the diagnosis of macrophage activation syndrome (MAS) complicating systemic juvenile idiopathic arthritis (s-JIA) during tocilizumab therapy.
Serum cytokine levels of neopterin, IL-18, C-X-C motif chemokine ligand 9, soluble tumor necrosis factor receptor (sTNFR)-I, and sTNFR-II were determined by enzyme-linked immunosorbent assay in 36 patients with MAS complicating s-JIA including 12 patients receiving tocilizumab. Furthermore, the serum sTNFR-II/I ratio was compared with the clinical features of MAS.
The levels of all serum cytokines at MAS diagnosis were significantly lower in the tocilizumab-treated group than in the tocilizumab-untreated group. In contrast, the serum sTNFR-II/I ratio at MAS diagnosis was comparable between the tocilizumab-treated and the tocilizumab-untreated groups. The receiver operating characteristic curve analysis revealed that the area under the curve and cut-off values of sTNFR-II/I ratio were 0.9722 and 4.71, respectively. The serum sTNFR-II/I ratio, which was significantly elevated in patients with MAS complicating s-JIA, was correlated positively with disease activity.
This is the first study to analyze the role of tocilizumab in modifying the serum levels of biomarkers used for the diagnosis of MAS complicating s-JIA. We found the biomarker for the diagnosis of MAS complicating s-JIA during tocilizumab therapy. We hope our results might be useful for the development of a new criteria for the diagnosis of MAS complicating s-JIA in patients treated with tocilizumab in future.
These findings suggest that the serum sTNFR-II/I ratio might be a useful indicator to evaluate disease activity in MAS complicating s-JIA and a useful diagnostic marker for the transition from active-phase s-JIA to MAS even in tocilizumab-treated patients.