Disease Severity in Dengue Patients Virus-Specific Plasmablast Response and Association between Magnitude of the
Disease Severity in Dengue Patients Virus-Specific Plasmablast Response and Association between Magnitude of the
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2015
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通讯作者：
Jr;S. Barratt-Boyes;Sean P Mcburney;Jared D. Evans;E. Marques;Amanda P Nascimento;Klécia M Smith;Tatiana M Soares De Melo;Marli T Garcia-Bates;Eduardo J M Cordeiro
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作者：
Jr;S. Barratt-Boyes;Sean P Mcburney;Jared D. Evans;E. Marques;Amanda P Nascimento;Klécia M Smith;Tatiana M Soares De Melo;Marli T Garcia-Bates;Eduardo J M Cordeiro
登革热是一种由感染登革热病毒(DENV)引起的全球性疾病，其范围从发热性疾病到具有严重并发症的急性疾病。继发感染使个体容易患上更严重的疾病，而B淋巴细胞可能通过产生抗体来增强感染，从而在这种现象中发挥作用。为了更好地了解登革热期间的急性B细胞反应，我们分析了来自巴西一家成人医院队列的外周B细胞，该队列患有不同临床严重程度的原发和继发性乙型脑炎病毒感染。与其他发热性疾病患者相比，登革热患者循环中的B细胞处于增殖、活化和凋亡状态。重型继发性乙型脑炎病毒感染患者的浆母细胞频率在发病后4~7d出现异常高峰，平均为46%，占B细胞的87%，fi明显高于轻症或原发感染患者。在严重继发性登革热病毒感染的个体中，平均70%的免疫球蛋白分泌细胞是登革热病毒fic。成浆细胞产生与异型登革热病毒血清型交叉反应的抗体，但对感染的血清型登革热病毒-3的反应性提高3倍。无论疾病的严重程度如何，浆母细胞频率与任何DENV血清型的急性血清中和抗体滴度无关。这些fi结果表明，在巴西成人的急性继发性登革热病毒感染中，fic和血清型交叉反应浆母细胞大量扩增，这与疾病的严重程度有关。《免疫学杂志》，2013,190：000-000。免疫C6/36后进行血清型特异性fic抗体染色，用血清型特异性fic引物进行两步套式逆转录聚合酶链式反应。AB采用抗-DENV-IgM-抗-DENV-Ig G双抗体夹心ELISA法检测急性和血小板白细胞计数，测定谷丙转氨酶和丙氨酸氨基转移酶浓度作为肝功能指标。在恢复期的fi病毒分离中，没有滴度的升高，在DENV-SPECIfic中没有出现。
Dengue is a globally expanding disease caused by infection with dengue virus (DENV) that ranges from febrile illness to acute disease with serious complications. Secondary infection predisposes individuals to more severe disease, and B lymphocytes may play a role in this phenomenon through production of Ab that enhance infection. To better define the acute B cell response during dengue, we analyzed peripheral B cells from an adult Brazilian hospital cohort with primary and secondary DENV infections of varying clinical severity. Circulating B cells in dengue patients were proliferating, activated, and apoptotic relative to individuals with other febrile illnesses. Severe secondary DENV infection was associated with extraordinary peak plasmablast frequencies between 4 and 7 d of illness, averaging 46% and reaching 87% of B cells, significantly greater than those seen in mild illness or primary infections. On average >70% of IgG-secreting cells in individuals with severe secondary DENV infection were DENV specific. Plasmablasts produced Ab that cross-reacted with heterotypic DENV serotypes, but with a 3-fold greater reactivity to DENV-3, the infecting serotype. Plasmablast frequency did not correlate with acute serum-neutralizing Ab titers to any DENV serotype regardless of severity of disease. These findings indicate that massive expansion of DENV-specific and serotype cross-reactive plasmablasts occurs in acute secondary DENV infection of adults in Brazil, which is associated with increasing disease severity. The Journal of Immunology , 2013, 190: 000–000. inoc-ulation C6/36 followed staining serotype-specific anti-DENV detection two-step nested RT-PCR performed using all four amplification with serotype-specific primers. Ab used anti-DENV IgM anti-DENV IgG ELISA on acute and platelet leukocyte counts, measurement aminotransferase and alanine aminotransferase con- centrations as indicators of liver function. and the presence of specific virus isolation, in the followed in the convalescent Sec- virus isolation, absent in rise in titer and of DENV-specific