University of Tennessee Health Science Center and Department of Veterans Affairs Research Service, Memphis, Tennessee.
St. Jude Children's Research Hospital, Memphis, Tennessee; and.
J Pediatric Infect Dis Soc. 2017 Jun 1;6(2):187-196. doi: 10.1093/jpids/piw070.
BACKGROUND.: 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.
METHODS.: 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.
RESULTS.: 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.
CONCLUSIONS.: 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 of emm 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.
尽管 A 组链球菌（GAS）感染相关疾病负担巨大，但人们对其自然感染后针对 GAS 抗原的人体免疫反应知之甚少。
我们评估了 41 名儿科患者连续 24 个月前瞻性获得的 195 份血清样本，这些患者经历了新的咽 GAS 获得。酶联免疫吸附试验用于确定针对 13 种共享 GAS 抗原和 18 种特定 M 肽的抗体的动力学和抗原特异性。测试的大多数抗原目前都被认为是疫苗候选物。
从经历 51 次新 GAS 获得的 41 名患者中分离出 12 种 GAS M 型，这些获得引起了针对测试的 31 种抗原中的至少 1 种的抗体反应（免疫意义上的新 GAS 获得）。针对 13 种共享抗原的免疫反应差异很大。针对平均 3.5 种共享抗原（范围 1-8）检测到抗体水平升高。在 51 个事件中的 32 个（63%）中观察到针对同源 M 肽的抗体反应。7 名患者获得了不止 1 种 GAS M 型。对于该患者针对同源 M 肽已有预存抗体的 M 型，没有新的免疫意义上的获得。在有新 GAS 获得的患者中，65%无症状，但针对 1 种或多种 GAS 抗原检测到免疫反应。在 67%的新 GAS 获得后观察到抗链球菌溶血素 O 和/或脱氧核糖核酸酶 B 的免疫反应。尽管针对同源 M 肽和/或共享抗原存在免疫反应，但仍有 20%的 41 名患者持续（>12 周）咽喉培养阳性。
可获得咽培养结果、GAS 分离株和前瞻性收集的 2 年观察期内的连续血清样本，为我们提供了一个独特的机会，可在新的咽 GAS 获得之前和之后评估儿科患者的血清学状态。除了针对同源 M 肽的抗体反应外，针对其余 GAS 抗原的免疫反应没有明显模式。对于该患者针对同源 M 肽已有预存升高水平抗体的 GAS emm 型，没有新的免疫意义上的获得。65%的新 GAS 获得没有引起症状但具有免疫意义的观察结果表明，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预防风湿热和风湿性心脏病的机会。
