Augmented ILT3/LILRB4 Expression of Peripheral Blood Antibody Secreting Cells in the Acute Phase of Kawasaki Disease

Augmented ILT3/LILRB4 Expression of Peripheral Blood Antibody Secreting Cells in the Acute Phase of Kawasaki Disease
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DOI:
10.1097/inf.0000000000002259
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发表时间:
2019-04-01
影响因子:
3.6
通讯作者:
Kumaki, Satoru
Kumaki, Satoru
中科院分区:
医学4区
文献类型:
--
作者:
Sugahara-Tobinai, Akiko;Inui, Masanori;Kumaki, Satoru

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背景:川崎(KD)是一种发生于儿童的急性全身性血管炎综合征。KD的临床症状和流行病学特征强烈表明,KD是由遗传易感患者中的不明感染因子引发的。此外,许多研究已经描述了B细胞在KD发展中的作用。为了深入了解KD患者B系细胞的体液免疫应答机制,我们检测了外周血抗体分泌细胞(ASC)和抑制性免疫受体,免疫球蛋白样转录物(ILT)/白细胞免疫球蛋白样受体(LILR),对每个B细胞亚群。方法:18名日本KD患者和13名健康对照者被招募参加这项研究。结果:KD患儿外周血单个核细胞中CD 19(+)B细胞数、各B细胞亚群的大小及ILT/LILR抑制亚型在B细胞亚群上的表达明显增加,大剂量静脉注射免疫球蛋白(IVIG)后,CD 19(+)CD 27(high)ASCs的表达明显减少。有趣的是,虽然ILT 2/LILRB 1的表达是普遍观察到的每个B细胞/ASCs亚群和IVIG后的水平没有显着差异,ILT 3/LILRB 4(B4)是唯一的表达只有ASCs,其表达后IVIG.Conclusions:在KD的急性期,ASCs的频率是高的增强B4表达,而它是降低与IVIG后B4表达降低。需要进一步研究B4在自身免疫性疾病和感染性疾病中ASCs的表达,以确认我们发现的意义。
Background: Kawasaki disease (KD) is an acute, systemic vasculitis syndrome that occurs in children. The clinical symptoms and epidemiologic features of KD strongly suggest that KD is triggered by unidentified infectious agents in genetically predisposed patients. In addition, a number of studies have described the role of B cells in the development of KD. To obtain a mechanistic insight into the humoral immune response of B-lineage cells in KD patients, we examined peripheral blood antibody secreting cells (ASCs) and inhibitory immunoreceptors, immunoglobulin-like transcript (ILT)/leukocyte immunoglobulin-like receptor (LILR), on each B cell subpopulation.Methods: Eighteen Japanese KD patients and thirteen healthy control subjects were recruited for this study. Their peripheral blood mononuclear cells were examined by flow cytometry for the number of CD19(+) B cells, the size of each B cell subset and the expression of the inhibitory isoforms of ILT/LILR on the B cell subset.Results: The frequency of CD19(+)CD27(high) ASCs was significantly increased in the acute phase of KD and reduced after high-dose intravenous immunoglobulin (IVIG) treatment. Interestingly, while ILT2/LILRB1 expression was ubiquitously observed on every B cell/ASCs subset and the level was not significantly different after IVIG, ILT3/LILRB4 (B4) was uniquely expressed on only ASCs, and its expression was significantly decreased after IVIG.Conclusions: In the acute phase of KD, the frequency of ASCs is high with augmented B4 expression, whereas it is lower with decreased B4 expression after IVIG. Further studies of B4 expression on ASCs in autoimmune and infectious diseases will be needed to confirm the significance of our findings.