INVESTIGADORES
KAMENETZKY Laura
artículos
Título:
Fcgamma;; receptor IIa (FCGR2A) Polymorphism Is Associated with Severe Respiratory Syncytial Virus Disease in Argentinean Infants
Autor/es:
HOLGADO, P.; RAIDEN, S.; SANANEZ, I.; SEERY, V.; DE LILLO, L.; MALDONADO, L.L.; KAMENETZKY, L.; GEFFNER, J.; ARRUVITO, L.
Revista:
Frontiers in Cellular and Infection Microbiology
Editorial:
Frorntiers Media S.A.
Referencias:
Año: 2020
ISSN:
2235-2988
Resumen:
BackgroundMost 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 andadaptive antiviral immunity. We investigated the relationship between FcγRIIa‐H131R polymorphism and RSV disease.MethodsBlood samples were collected from 182 infants ≤24‐month‐old (50 uninfected, 114 RSV‐infected with moderate course and 18suffering severe disease). FcγRIIa‐H131R SNP genotypic frequencies (HH, HR, RR) and anti‐RSV IgG1, IgG2 and IgG3 levels werestudied.ResultsGenotypic frequencies for FcγRIIa‐H131R SNP were comparable between uninfected and RSV‐infected infants. In contrast, we found asignificant 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 moderateRSV-infected infants, severe patients showed higher levels of anti-RSV IgG1 and IgG3.ConclusionsWe found an association between an FcγRIIa (H131) polymorphism and severe RSV disease, which points towards a critical role forinteractions between FcγRs and immune complexes in RSV pathogenesis. This genetic factor could also predict the worse outcomeand identify those infants at risk during hospitalization.Contribution to the fieldRespiratory syncytial virus (RSV) infection is the commonest cause of bronchiolitis in infants globally but there is still noexplanation to the higher severity observed at ages when infants have greater levels of maternal antibodies. On the other hand,RSV vaccine candidates are evaluated based on their induction of RSV neutralizing Abs. However, antibodies can also influence theoutcome of diseases by activating effector functions through the receptors for the Fc portion of IgG (FcγRs). Changes at geneticlevel may affect the functionality of FcγRs. The most functionally relevant single nucleotide polymorphisms (SNPs) described forFcγRIIA involves a change of arginine (R) to a histidine (H) at position 131, affecting the affinity for IgG subclasses. There is no dataon the role of this SNP in RSV context. This study reveals for the first time an association between an FcγRIIa (H131) polymorphismand severe RSV disease, which points towards a critical role for the interactions between FcγRs and immune complexes containingIgG in RSV pathogenesis. This genetic factor could also help to predict the worse outcome and identify those infants at risk ofsevere disease at time of hospitalization