Department of Immunology, The University of Texas Southwestern Medical Center, NA2.200, 6000 Harry Hines Blvd., Dallas, TX, 75390-9093, USA.
Department of Pediatrics, The University of Texas Southwestern Medical Center, NA2.200, 6000 Harry Hines Blvd., Dallas, TX, 75390-9093, USA.
J Clin Immunol. 2021 Jul;41(5):1031-1047. doi: 10.1007/s10875-021-00993-w. Epub 2021 Mar 3.
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.
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。本研究比较了一组幼儿的抗体特异性，以确定血清阳性与血清阴性反应之间的差异。
使用含有 110 种不同抗原的微流控芯片，对 197 名 1 至 2 岁幼儿的血清 IgM 和 IgG 抗体反应进行评估。从第 1 年到第 2 年进行纵向分析。比较 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 反应的定量变化制定分层。调查了与 IgG 反应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 反应将幼儿分为低、中、高反应组。高反应组（17%）对多种 RNA 和 DNA 病毒（如呼吸道合胞病毒、EB 病毒、腺病毒、柯萨奇病毒）产生了升高的 IgG 反应，这与对减毒活病毒疫苗和某些自身抗原的反应增强有关。该高反应组与妊娠糖尿病和年龄较大有关。遗传分析在两名高反应者中发现了 IL2RB、TNFSF4 和 INS 基因的多态性，这些多态性与他们升高的细胞因子水平和湿疹和哮喘的临床病史有关。
对幼儿血清 IgG 分析显示，病毒、减毒活疫苗和某些自身抗原的抗体反应强度之间存在相关性。低反应组的总体反应较弱，包括对疫苗的反应。血清抗体筛查还可识别对不常见感染（西尼罗河病毒、细小病毒、结核病）有 IgG 反应的个体。抗体反应的特征描述加上遗传风险等位基因的鉴定，为识别具有临床疾病风险增加的儿童提供了机会。
