We aimed to assess the kinetics of the release of proinflammatory cytokines and to clarify clinical usefulness as an indicator of the disease activity in human parechovirus type 3 virus (HPeV3)-induced sepsis-like syndrome. We measured serum levels of neopterin, interleukin (IL)-6 and the soluble forms of tumor necrosis factor (TNF) receptor types I (sTNF-RI) and II (sTNF-RII). Serum samples were obtained from 12 patients with HPeV3-induced sepsis-like syndrome and 28 healthy children. Disease course after onset was divided into 3 phases: early (day 1–2), peak (day 3–6) and recovery (day 9–16) phases. Serum IL-6 levels rapidly and markedly elevated in early phase and gradually decreased to those in healthy children in recovery phase. Furthermore, serum neopterin, sTNFR-I and sTNFR-II levels increased rapidly and markedly in onset phase and remained elevated in peak phase. These levels gradually decreased in recovery phase. Serum IL-18 levels increased from onset phase to peak phase and decreased in recovery phase. These results indicate that proinflammatory cytokines, in particular, interferon gamma, TNF-α and IL-18 are closely related to the development of HPeV3-induced sepsis-like syndrome. Serum levels of these cytokines might be a useful indicator of the disease activity.
BackgroundMacrophage activation syndrome (MAS) is a severe life-threatening condition that complicates systemic juvenile idiopathic arthritis (s-JIA). Differentiating MAS from these conditions is essential for selecting appropriate therapeutic interventions in a timely manner. However, there is no definite biomarkers that can effectively diagnose MAS.ObjectivesOur study aimed to compare the accuracy of serum biomarkers for the diagnosis of MAS complicating s-JIA and to investigate the clinical significance of serum neopterin levels as an indicator of disease activity and diagnosis of MAS complicating s-JIA.MethodsSerum cytokine levels (neopterin, IL-18, and CXCL9 and soluble tumor necrosis factor receptor type I (sTNFR-I) and II were determined by enzyme-linked immunosorbent assay in 78 patients with s-JIA, including 21 with MAS. The accuracy of these levels for the diagnosis of MAS were compared. Next, serum neopterin levels, in total 125 patients with s-JIA, including 30 with MAS, 15 with Epstein–Barr virus-induced hemophagocytic lymphohistiocytosis (EBV-HLH), and 15 with Kawasaki disease (KD), as well as 28 healthy controls (HCs) were analysed. Results were compared with the clinical features of MAS.ResultsReceiver operating characteristic curve analysis revealed area under the curve values and cut off values of neopterin, IL-18, CXCL9, sTNFR-II/I ratio and ferritin were 0.9465/19.5nmol/l, 0.8895/69250ng/ml, 0.9333/3130pg/ml, 0.9395/3.796 and 0.8671/2560ng/ml, respectively. Serum neopterin levels were significantly elevated in patients with MAS and EBV-HLH compared with those in patients with acute-phase s-JIA and KD. Serum neopterin levels profoundly and rapidly increased as MAS developed and correlated positively with disease activity.ConclusionSerum neopterin levels may be used as a promising indicator of disease activity in s-JIA and MAS and for evaluating it. It may also be a useful marker to diagnose the transition to MAS from active-phase s-JIA.References[1] Huber C, et al. J Exp Med1984;160:310-6.[2] Bracaglia C, et al. Ann Rheum Dis2017;76:166-72.[3] Shimizu M, et al. Clin Exp Immunol2018;191:349-355.Disclosure of InterestsNone declared
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