Instituto de Investigaciones Biomédicas en Retrovirus y SIDA (INBIRS), Universidad de Buenos Aires, CONICET, Ciudad de Autónoma Buenos Aires, Argentina.
Hospital General de Niños "Pedro de Elizalde", Ciudad Autónoma de Buenos Aires, Argentina.
Front Cell Infect Microbiol. 2020 Dec 18;10:607348. doi: 10.3389/fcimb.2020.607348. eCollection 2020.
Most patients with respiratory syncytial virus (RSV) infection requiring hospitalization have no risk factors for severe disease. Genetic variation in the receptor for the Fc portion of IgG (FcγR) determines their affinity for IgG subclasses driving innate and adaptive antiviral immunity. We investigated the relationship between FcγRIIa-H131R polymorphism and RSV disease.
Blood samples were collected from 182 infants ≤24-month-old (50 uninfected, 114 RSV-infected with moderate course and 18 suffering severe disease). FcγRIIa-H131R SNP genotypic frequencies (HH, HR, RR) and anti-RSV IgG1, IgG2 and IgG3 levels were studied.
Genotypic frequencies for FcγRIIa-H131R SNP were comparable between uninfected and RSV-infected infants. In contrast, we found a significant higher frequency of HH genotype in severe RSV-infected children compared to moderate patients. Among severe group, HH infants presented more factors associated to severity than HR or RR patients did. Furthermore, compared to moderate RSV-infected infants, severe patients showed higher levels of anti-RSV IgG1 and IgG3.
We found an association between an FcγRIIa (H131) polymorphism and severe RSV disease, which points towards a critical role for interactions between FcγRs and immune complexes in RSV pathogenesis. This genetic factor could also predict the worse outcome and identify those infants at risk during hospitalization.
大多数需要住院治疗的呼吸道合胞病毒(RSV)感染患者没有严重疾病的风险因素。Fc 段 IgG 受体(FcγR)的遗传变异决定了其与 IgG 亚类的亲和力,从而驱动先天和适应性抗病毒免疫。我们研究了 FcγRIIa-H131R 多态性与 RSV 疾病之间的关系。
收集了 182 名≤24 个月大的婴儿的血液样本(50 名未感染,114 名 RSV 感染且病程中度,18 名感染且病情严重)。研究了 FcγRIIa-H131R SNP 基因型频率(HH、HR、RR)和抗 RSV IgG1、IgG2 和 IgG3 水平。
未感染和 RSV 感染婴儿的 FcγRIIa-H131R SNP 基因型频率相似。相比之下,我们发现严重 RSV 感染患儿的 HH 基因型频率明显高于中度患儿。在严重组中,HH 婴儿比 HR 或 RR 婴儿更易出现与严重程度相关的因素。此外,与中度 RSV 感染婴儿相比,严重 RSV 感染患儿的抗 RSV IgG1 和 IgG3 水平更高。
我们发现 FcγRIIa(H131)多态性与严重 RSV 疾病之间存在关联,这表明 FcγR 与免疫复合物之间的相互作用在 RSV 发病机制中起着关键作用。这种遗传因素还可以预测病情恶化的情况,并在住院期间识别出有风险的婴儿。