LAUSR

* Seigo Okada [email protected] Although the standard treatment for Kawasaki disease (KD) is intravenous immunoglobulin (IVIG) combined with oral aspirin, 18% of 1st IVIG is refractory [1]. Recently, the efficacy of immunomodulatory drugs for IVIG-resistant KD, such as prednisolone, infliximab (IFX), and cyclosporine (CsA), has been reported [2–5]. However, optimal immunomodulatory therapy for IVIG-resistant KD has not yet been established. In this study, we evaluated the immunomodulatory effects of oral CsA (n = 6) compared with IFX (n = 51) (control group, which has different and specific therapeutic targets) for IVIG-resistant KD (Supplementary Fig. 1). All patients were administered two cycles of IVIG (2 g/kg/dose) before treatment. The kinetics of peripheral blood mononuclear cells (PBMCs) were assessed by flow cytometry according to a previous study [6]. Coronary artery lesions were defined as a Z score of coronary diameters ≥ + 2.5, measured by two-dimensional echocardiography 1 month after onset [1, 7]. CsA administration was started on day 9 (9–21) at a dose of 4 mg/kg/day and continued for 11 (7–14) days (Supplementary Table 1). All patients showed complete defervescence after CsA therapy. In the control group, patients received IFX at a dose of 5 mg/kg on day 8 (4–15). There were no significant differences in the side effects between the groups. The absolute number of CD8+HLA-DR+ cells, but not other PBMCs, significantly decreased after CsA therapy (P = 0.047) (Fig. 1). In the control group, the absolute number of CD14+ monocytes decreased after IFX therapy (P = 0.031). The absolute numbers of total CD4+, CD8+, CD4+HLA-DR+, and CD8+HLA-DR+ cells significantly increased after IFX therapy (all P ≤ 0.001). T cells are suppressed during the acute phase and are ameliorated after IVIG or the convalescent phase [8, 9]. However, IVIG-resistant KD patients show T cell activation even during the acute phase [9, 10]. Therefore, CsA may be a useful option in this population, especially with CD8+ T cell activation. Based on the results in which different kinetics in PBMCs were observed according to the therapies, different immune mechanisms affecting the efficacy of the drugs might be involved in immunoglobulin-resistant KD. There are some limitations to our study that might lead to biased results, such as a small number of participants and an age effect on the T cell population. Nevertheless, this study provides new insights into immunomodulatory therapy for KD. Further multicenter and long-term studies are required to explore the immunosuppressive mechanism of CsA in patients with KD.