Prospective Longitudinal Analysis of Immune Responses in Pediatric Subjects After Pharyngeal Acquisition of Group A Streptococci.
Prospective Longitudinal Analysis of Immune Responses in Pediatric Subjects After Pharyngeal Acquisition of Group A Streptococci.
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DOI：
10.1093/jpids/piw070
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发表时间：
2017-06-01
影响因子：
3.2
通讯作者：
Dale JB
中科院分区：
文献类型：
--
作者：
Hysmith ND;Kaplan EL;Cleary PP;Johnson DR;Penfound TA;Dale JB
在儿童中新获得A组链球菌之前和之后，确定了对一组共享和类型特异性抗原的免疫应答。对共有抗原的抗体应答是可变的。M肽特异性抗体反应后检测到63%的新收购。尽管与A组链球菌（GAS）感染相关的疾病负担显著，但关于天然感染后对GAS抗原的人类免疫应答知之甚少。我们评估了在连续24个月期间从41名经历新的咽部GAS采集的儿科受试者中前瞻性获得的195份血清样本。酶联免疫测定法用于确定针对13种共享GAS抗原和18种类型特异性M肽的抗体的动力学和抗原特异性。大多数测试的抗原目前被认为是候选疫苗。从41名受试者中回收了12种M型GAS，这些受试者经历了51次新的GAS采集，这些采集引起了针对31种检测抗原中至少1种的抗体应答（免疫学显著的新GAS采集）。对13种共有抗原的免疫应答是高度可变的。针对平均3.5种共有抗原（范围，1-8）检测到抗体水平增加。在51次发作中的32次（63%）中观察到对同源M肽的抗体应答。7名受试者获得了超过1 M的GAS。没有新的具有免疫学意义的M型获得，受试者针对该M型先前存在针对同源M肽的抗体。在患有新GAS的受试者中，65%无症状，但检测到针对1种或多种GAS抗原的免疫应答。在67%的新GAS采集后观察到对链球菌溶血素O和/或脱氧核糖核酸酶B的免疫应答。尽管对同源M肽和/或共有抗原有免疫应答，但41名受试者中有20%返回了持续阳性（>12周）的咽喉培养结果。在为期2年的观察期内前瞻性收集的咽喉培养结果、GAS分离株和系列血清样本的可用性为我们提供了一个独特的机会，以评估儿科受试者在新的咽部GAS采集前后的血清学状态。除了对同源M肽的抗体应答外，未观察到对其余GAS抗原的免疫应答的明确模式。没有新的具有免疫学意义的emm型GAS的获得，受试者针对这些GAS具有预先存在的针对同源M肽的抗体水平升高。观察到65%的新GAS采集没有引起任何症状，但具有免疫学意义，这表明大多数感染未被检测到，这将导致错过使用适当的抗菌治疗进行风湿热和风湿性心脏病一级预防的机会。
Immune responses to a panel of shared and type-specific antigens before and after new acquisitions of group A streptococci in children were determined. Antibody responses to shared antigens were variable. M peptide-specific antibody responses were detected after 63% of the new acquisitions. Despite the significant burden of disease associated with infection by group A streptococcus (GAS), little is known about the human immune response to GAS antigens after natural infection. We evaluated 195 serum samples obtained prospectively over a consecutive 24-month period from 41 pediatric subjects who experienced a new pharyngeal GAS acquisition. An enzyme-linked immunoassay was used to determine the kinetics and antigen specificity of antibodies against 13 shared GAS antigens and 18 type-specific M peptides. The majority of the antigens tested are currently being considered as vaccine candidates. Twelve M types of GAS were recovered from 41 subjects who experienced 51 new GAS acquisitions that elicited antibody responses against at least 1 of the 31 antigens tested (immunologically significant new GAS acquisitions). The immune responses to the 13 shared antigens were highly variable. Increases in antibody levels were detected against a mean of 3.5 shared antigens (range, 1–8). Antibody responses to the homologous M peptide were observed in 32 (63%) of the 51 episodes. Seven subjects acquired more than 1 M type of GAS. There were no new immunologically significant acquisitions of an M type against which the subject had preexisting antibodies to the homologous M peptide. Of the subjects with new GAS acquisition, 65% were asymptomatic, yet immune responses were detected against 1 or more GAS antigens. Immune responses to streptolysin O and/or deoxyribonuclease B were observed after 67% of the new GAS acquisitions. Persistently positive (>12 weeks) throat culture results were returned for 20% of the 41 subjects despite immune responses to homologous M peptides and/or shared antigens. The availability of throat culture results, GAS isolates, and serial serum samples collected prospectively over a 2-year period of observation provided a unique opportunity for us to assess the serologic status of pediatric subjects before and after new pharyngeal acquisitions of GAS. With the exception of antibody responses to the homologous M peptides, no clear pattern of immune responses against the remaining GAS antigens was seen. There were no new immunologically significant acquisitions ofemm types of GAS against which the subjects had preexisting elevated levels of antibodies against the homologous M peptide. The observation that 65% of new GAS acquisitions caused no symptoms yet were immunologically significant suggests that the majority of infections are not detected, which would result in missed opportunities for primary prevention of rheumatic fever and rheumatic heart disease with appropriate antimicrobial therapy.
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影响因子：
5.5
作者：
Madore, Dace V.;Meade, Bruce D.;Rubin, Fran;Deal, Carolyn;Lynn, Freyja
通讯作者：
Lynn, Freyja
影响因子：
3.1
作者：
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HANDLEY, J
影响因子：
6.4
作者：
Batzloff, MR;Hayman, WA;Good, MF
通讯作者：
Good, MF
影响因子：
3.1
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通讯作者：
Lei, Benfang
影响因子：
3.1
作者：
Park, HS;Cleary, PP
通讯作者：
Cleary, PP