The IL-10 polarized cytokine pattern in innate and adaptive immunity cells contribute to the development of FVIII inhibitors
The IL-10 polarized cytokine pattern in innate and adaptive immunity cells contribute to the development of FVIII inhibitors
复制标题
先天性和适应性免疫细胞中的 IL-10 极化细胞因子模式有助于 FVIII 抑制剂的开发
作者：
Amanda CO Silveira;Marcio A. P. Santana;Isabella G Ribeiro;D. Chaves;O. Martins
血友病A（Hemophilia A，HA）是一种X染色体连锁遗传性出血性疾病，由凝血因子VIII（凝血因子VIII）的定性或定量缺陷引起。针对FVIII的抗体（也称为抑制剂）阻断FVIII的促凝血活性;因此，损害HA患者的止血活性。抑制剂产生背后的免疫学事件的确切机制仍不清楚。本研究旨在了解HA患者对FVIII的免疫反应，这些患者对抑制剂呈阳性[HAα-FVIII（+）]或阴性[HAα-FVIII（-）]。[10]先天性和适应性免疫细胞存在于参与者的外周血进行了表征。TNF-α阳性单核细胞和中性粒细胞、IL-5阳性单核细胞、IL-4阳性中性粒细胞的频率以及IL-10阳性中性粒细胞和T细胞的频率增加。来自HAα-FVIII（−）患者的T细胞表达几乎所有细胞因子的水平升高。相比之下，HAα-FVIII（+）患者的CD 4+和CD 8 + T细胞中所有细胞因子水平均较低，IL-10除外。HAα-FVIII（-）患者的B细胞表达IL-4水平升高，而HAα-FVIII（+）患者的B细胞表达IL-10水平升高。结论HAα-FVIII（+）患者的先天性和适应性免疫细胞的总体细胞因子谱显示抗炎/调节模式，HAα-FVIII（-）患者的混合模式偏向炎症细胞因子谱。这些特征的发生似乎与存在FVIII抑制剂相关。
BackgroundHemophilia A (HA) is an X-linked inherited bleeding disorder, resulting from a qualitative or quantitative deficiency of clotting factor VIII (FVIII). Antibodies against FVIII, also called inhibitors, block the procoagulant activity of FVIII; thus, impairing hemostatic activity in patients with HA. The exact mechanism underlying the immunological events behind the development of inhibitors remains unknown. This study aimed to understand immune response to FVIII in patients with HA who were either positive [HAα-FVIII(+)] or negative [HAα-FVIII(−)] for inhibitors.MethodsCytokine profiles [interferon-γ (IFN − γ), tumor necrosis factor-α (TNF-α), interleukin-4 (IL-4), IL-5, and IL-10] of innate and adaptive immune cells present in the peripheral blood of participants were characterized.ResultsPresence of inhibitors was significantly associated with decreased frequencies of TNF-α-positive monocytes and neutrophils, IL-5-positive monocytes, IL-4-positive neutrophils, and increased frequencies of IL-10-positive neutrophils and T cells. T cells from HAα-FVIII(−) patients expressed increased levels of almost all cytokines. In contrast, HAα-FVIII(+) patients showed lower levels of all cytokines in CD4+ and CD8+ T cells, except IL-10. B cells from HAα-FVIII(−) patients expressed increased levels of IL-4 while those from HAα-FVIII(+) patients expressed increased levels of IL-10.ConclusionsThe global cytokine profiles of innate and adaptive immune cells showed an anti-inflammatory/regulatory pattern in HAα-FVIII(+) patients and a mixed pattern, with a bias toward inflammatory cytokine profile, in HAα-FVIII(−) patients. The occurrence of these profiles seems to be associated with presence FVIII inhibitors.
影响因子：
2.9
作者：
DAVIE, EW;FUJIKAWA, K;KISIEL, W
通讯作者：
KISIEL, W
因子 VIII 替代疗法的优化：结构研究能否帮助规避抗体抑制剂？
影响因子：
6.5
作者：
SpiegelJr,PClint;Stoddard,BarryL
通讯作者：
Stoddard,BarryL