Circulating CD3 + HLA-DR + Extracellular Vesicles Are Not Increased in the Acute Phase of Kawasaki Disease
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MEDICINE
Circulating CD3+HLA-DR+ Extracellular Vesicles Are Not Increased in the Acute Phase of Kawasaki Disease Masayuki Nagasawa 1 & Miho Ashiarai 1 & Ryutaro Oba 2 & Kinya Nagata 2 Accepted: 26 March 2020 / Published online: 2 May 2020 # Springer Nature Switzerland AG 2020
Abstract Kawasaki disease (KD) is an acute inflammatory illness with unknown etiology. We prospectively measured novel T cell–derived CD3+HLA-DR+ extracellular vesicles (EVs), which specifically reflect T cell activation in the acute phase of KD, after IVIG treatment, and in convalescence phase in 35 newly diagnosed KD patients. There was little increase in CD3+HLA-DR+ EVs before IVIG treatment and no significant change after IVIG treatment and in the convalescence phase. This result supports the view that the involvement of acquired immunity in the pathogenesis of KD is less likely. Keywords Acquired immunity . Extracellular vesicles . Innate immunity . Kawasaki disease . T cell
Kawasaki disease (KD) is an acute inflammatory illness with unknown etiology. KD commonly affects children less than 4 years of age. A dysregulated immune response to some environmental factors or infectious agents is associated with the pathogenesis of KD. The immune response is mainly divided into innate immunity and acquired immunity. Which of these is mainly involved in the pathogenesis of KD is controversial [1]. KD commonly presents as an acute and transient illness with a recurrence rate as low as 2 to 3%. Acquired immunity is usually immature during the period of life when individuals are most susceptible to KD. We recently reported that the levels of soluble Sortilin— released from activated platelets—are increased and strongly reflect disease activity in the acute phase of KD [2]. Thus, the innate immune response may be involved in KD [3]. However, it has been reported that T cells, which are the main constituent of acquired immunity, are activated in the acute phase of KD, and that This article is part of the Topical Collection on Medicine * Masayuki Nagasawa [email protected] 1
Department of Pediatrics, Musashino Red Cross Hospital, 1-26-1, Kyonan-cho, Musashino, Tokyo 180-8610, Japan
2
Division of Advanced Technology and Development, BML Inc., Saitama, Japan
this activation affects the response to treatment with intravenous immunoglobulin (IVIG) [4, 5]. A genetic polymorphism involved in the T cell activation pathway was recently implicated in KD [6, 7]. Extracellular vesicles (EVs) are small vesicles (< 2 μm in diameter) that are enclosed by a plasma membrane. EVs are released from various cell types and are involved in intercellular signal transduction, and have an important physiological role [8]. In a recent proteomic study, we identified novel T cell–derived EVs (CD3 + CD8 + EVs, CD3 + CD4 + EVs, and CD3 + HLADR+ EVs), established an assay for these EVs, and reported that CD3+HLA-DR+ EVs reflect T cell activation status in in vitro as well as in vivo [9]. Presently, to evaluate the activation status of T cells in KD, we prospectively measu
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