Departamento de Microbiologia, Laboratório de Virologia Básica e Aplicada, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil.
Serviço de Pesquisa, Gerência de Desenvolvimento Técnico Científico, Fundação Hemominas, Belo Horizonte, Minas Gerais, Brazil.
J Med Virol. 2022 Feb;94(2):683-691. doi: 10.1002/jmv.27432. Epub 2021 Nov 11.
Prevalence of hepatitis C virus (HCV) is high in hemophilia A patients and the development of FVIII inhibitor is another challenge in the management of these individuals. The influence of HCV infection in the occurrence of inhibitors was investigated by the comparison of clinical and laboratory data from noninfected (NI, n = 96) and chronically HCV-infected (HCV, n = 58) hemophilia A patients. Concentrations of plasmatic cytokines (IL-2, IL-4, IL-6, IL-10, TNF, IFN-γ, and IL-17A) and chemokines (CCL2, CCL5, CXCL8, CXCL9, and CXCL10) were quantified from patients' samples. The results showed that older age, use of cryoprecipitate and fresh frozen plasma, and severe hemophilia were associated with HCV infection, whereas exclusive use of virus inactivated clotting factors was a protector factor to acquiring HCV infection. HCV infection was strongly associated with low levels of inhibitor (OR = 20.53, p < 0.001). Patients with a history of inhibitor (INB+) presented a mixed immune profile characterized by higher levels of pro-and anti-inflammatory cytokines than those without a history of inhibitor (INB-). The highest levels of CCL2 and CXCL8 were seen in HCV , whereas CXCL9 and CXCL10 in HCV . Heatmap analysis of the set of cytokines and chemokines concentration distributed HCV patients into two distinct clusters, HCV and HCV , both characterized by low concentrations of IL-4, while noninfected patients were grouped in a single block regardless of inhibitor development history (NI ). This finding suggests that the strong association between HCV infection and low levels of factor VIII inhibitors might be due to the modulation of the cytokine and chemokine network established by the antiviral response.
丙型肝炎病毒（HCV）在血友病 A 患者中流行率很高，而 FVIII 抑制剂的产生是此类患者管理中的另一个挑战。本研究通过比较未感染（NI，n=96）和慢性 HCV 感染（HCV，n=58）的血友病 A 患者的临床和实验室数据，研究了 HCV 感染对抑制剂产生的影响。从患者样本中定量检测了血浆细胞因子（IL-2、IL-4、IL-6、IL-10、TNF、IFN-γ 和 IL-17A）和趋化因子（CCL2、CCL5、CXCL8、CXCL9 和 CXCL10）的浓度。结果显示，年龄较大、使用冷沉淀和新鲜冰冻血浆以及重度血友病与 HCV 感染相关，而单独使用病毒灭活凝血因子是预防 HCV 感染的保护因素。HCV 感染与低水平抑制剂强烈相关（OR=20.53，p<0.001）。有抑制剂病史（INB+）的患者表现出混合免疫特征，其促炎和抗炎细胞因子水平高于无抑制剂病史（INB-）的患者。HCV 患者的 CCL2 和 CXCL8 水平最高，而 HCV 患者的 CXCL9 和 CXCL10 水平最高。细胞因子和趋化因子浓度的热图分析将 HCV 患者分为两个不同的簇，HCV 和 HCV ，两者均表现出低水平的 IL-4，而无论抑制剂的发展历史如何，未感染的患者均被分为一组（NI）。这一发现表明，HCV 感染与 FVIII 抑制剂低水平之间的强相关性可能是由于抗病毒反应所建立的细胞因子和趋化因子网络的调节所致。
