Stimulation of the primary anti-HIV antibody response by IFN-α in patients with acute HIV-1 infection
Stimulation of the primary anti-HIV antibody response by IFN-α in patients with acute HIV-1 infection
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DOI：
10.1189/jlb.1007675
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发表时间：
2008-04-01
影响因子：
5.5
通讯作者：
Emilie, Dominique
中科院分区：
文献类型：
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作者：
Adalid-Peralta, Laura;Godot, Veronique;Emilie, Dominique
I型干扰素是在小鼠体内产生抗病毒抗体所需要的；在人类病毒感染期间，它们是否也刺激体内的主要抗体反应尚不清楚。这是在急性感染HIV-1并接受干扰素-α2b治疗的患者中进行评估的。将急性HIV-1感染患者随机分为两组，A组(60例)单独接受抗逆转录病毒治疗，B组(30例)联合应用聚乙二醇化干扰素-α2b治疗14周。通过血清样本的免疫印迹(WB)分析，在32周内监测抗HIV抗体的出现。干扰素-α2b治疗可刺激抗HIV抗体的产生。在末次注射干扰素-α2b后32周和19周，B组和A组分别有8.5%(6.5%~10.0%)和7.0%(5.0%~10.0%)条带(P<；0.054)，且B组的条带强度较强(p18、p24、p34、p40和p55HIV抗原的条带强度较强)。干扰素-α2b治疗还增加了循环中肿瘤坏死因子家族的B细胞激活因子的浓度(P<；0.001)和体外产生的IL-12(P<；0.05)，反映了它对先天免疫细胞的影响。在36周停止抗逆转录病毒治疗后，B组的HIV复制反弹低于A组(P<；0.05)。因此，I型干扰素刺激急性HIV-1感染患者新出现的抗HIV免疫反应，从而改善对HIV复制的控制。因此，I型干扰素在人类有效的抗病毒免疫反应的发展中至关重要，包括产生抗病毒抗体。
Type I IFNs are needed for the production of antiviral antibodies in mice; whether they also stimulate primary antibody responses in vivo during human viral infections is unknown. This was assessed in patients acutely infected with HIV- 1 and treated with IFN-alpha 2b. Patients with acute HIV-1 infection were randomized to receive antiretroviral therapy alone (Group A, n = 60) or combined for 14 weeks with pegylated- IFN-alpha 2b (Group B, n = 30). Emergence of anti- HIV antibodies was monitored during 32 weeks by Western blot (WB) analyses of serum samples. IFN-alpha 2b treatment stimulated the production of anti- HIV antibodies. On Week 32, 19 weeks after the last IFN-alpha 2b administration, there were 8.5 (6.5-10.0) HIV WB bands (median, interquartile range) in Group B and 7.0 (5.0-10.0) bands in Group A (P < 0.054), and band intensities were stronger in Group B (P < 0.05 for p18, p24, p34, p40, and p55 HIV antigens). IFN-alpha 2b treatment also increased circulating concentrations of the B cellactivating factor of the TNF family (P < 0.001) and ex vivo production of IL-12 (P < 0.05), reflecting its effect on innate immune cells. Withdrawal of antiretroviral treatment on Week 36 resulted in a lower rebound of HIV replication in Group B than in Group A (P < 0.05). Therefore, type I IFNs stimulate the emerging anti-HIV immune response in patients with acute HIV-1 infection, resulting in an improved control of HIV replication. Type I IFNs are thus critical in the development of efficient antiviral immune responses in humans, including the production of antiviral antibodies.