Serum IgG Profiling of Toddlers Reveals a Subgroup with Elevated Seropositive Antibodies to Viruses Correlating with Increased Vaccine and Autoantigen Responses.

Serum IgG Profiling of Toddlers Reveals a Subgroup with Elevated Seropositive Antibodies to Viruses Correlating with Increased Vaccine and Autoantigen Responses.
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DOI:
10.1007/s10875-021-00993-w
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发表时间:
2021-07
影响因子:
9.1
通讯作者:
van Oers NSC
van Oers NSC
中科院分区:
医学2区
文献类型:
--
作者:
Pichilingue-Reto P;Raj P;Li QZ;Dozmorov I;Karp DR;Wakeland EK;Nelson M;Gruchalla RS;de la Morena MT;van Oers NSC

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人类抗体库是针对感染、微生物组、疫苗接种和环境暴露而形成的。在一组幼儿中比较这种抗体应答的特异性,以确定血清阳性与血清阴性应答之间的差异。用含有110种不同抗原的微流控阵列对197名1岁和2岁幼儿的血清IgM和IgG抗体反应性进行评估。从第1年到第2年进行纵向分析。比较了RNA和DNA病毒、细菌、减毒活疫苗、灭活疫苗和亚单位疫苗以及自身抗原的血清阳性率。根据IgG应答的定量变化进行分层。研究了与IgG应答相关的各种免疫系统疾病的临床表现和先前已知的遗传风险等位基因。IgG反应分层幼儿低,中度,高响应组。高水平组(17%)对多种RNA和DNA病毒的IgG应答升高(例如,呼吸道合胞病毒、爱泼斯坦-巴尔病毒、腺病毒、柯萨奇病毒),并且这与对减毒活病毒疫苗和某些自身抗原的应答增加相关。这一高水平组更可能与妊娠糖尿病和年龄较大有关。遗传分析确定了IL 2 RB,TNFSF 4和INS基因的多态性在两个高响应者的个人,与他们的细胞因子水平升高和湿疹和哮喘的临床病史。幼儿的血清IgG分析揭示了对病毒、减毒活疫苗和某些自身抗原的抗体应答幅度之间的相关性。低反应组的总体反应要弱得多,包括对疫苗的反应。血清抗体筛查还可以识别对不太常见的感染(西尼罗河病毒,细小病毒,结核病)有IgG反应的个体。抗体应答的表征与遗传风险等位基因的鉴定相结合,为鉴定临床疾病风险增加的儿童提供了机会。在线版本包含补充材料,可通过10.1007/s10875-021-00993-w获得。
The human antibody repertoire forms in response to infections, the microbiome, vaccinations, and environmental exposures. The specificity of such antibody responses was compared among a cohort of toddlers to identify differences between seropositive versus seronegative responses. An assessment of the serum IgM and IgG antibody reactivities in 197 toddlers of 1- and 2-years of age was performed with a microfluidic array containing 110 distinct antigens. Longitudinal profiling was done from years 1 to 2. Seropositivity to RNA and DNA viruses; bacteria; live attenuated, inactive, and subunit vaccines; and autoantigens was compared. A stratification was developed based on quantitative variations in the IgG responses. Clinical presentations and previously known genetic risk alleles for various immune system conditions were investigated in relation to IgG responses. IgG reactivities stratified toddlers into low, moderate, and high responder groups. The high group (17%) had elevated IgG responses to multiple RNA and DNA viruses (e.g., respiratory syncytial virus, Epstein-Barr virus, adenovirus, Coxsackievirus) and this correlated with increased responses to live attenuated viral vaccines and certain autoantigens. This high group was more likely to be associated with gestational diabetes and an older age. Genetic analyses identified polymorphisms in the IL2RB, TNFSF4, and INS genes in two high responder individuals that were associated with their elevated cytokine levels and clinical history of eczema and asthma. Serum IgG profiling of toddlers reveals correlations between the magnitude of the antibody responses towards viruses, live attenuated vaccines, and certain autoantigens. A low responder group had much weaker responses overall, including against vaccines. The serum antibody screen also identifies individuals with IgG responses to less common infections (West Nile virus, parvovirus, tuberculosis). The characterization of the antibody responses in combination with the identification of genetic risk alleles provides an opportunity to identify children with increased risk of clinical disease. The online version contains supplementary material available at 10.1007/s10875-021-00993-w.
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发表时间: 2014-07-01
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