ABSTRACT
Analysing human genetic variation provides a powerful tool in understanding risk factors for disease. Toxoplasma gondii acquired by the mother can be transmitted to the fetus. Infants with the most severe clinical signs in brain and eye are those infected early in pregnancy when fetal immunity is least well developed. Genetic analysis could provide unique insight into events in utero that are otherwise difficult to determine. We tested the hypothesis that propensity for T. gondii to cause eye disease is associated with genes previously implicated in congenital or juvenile onset ocular disease. Using mother-child pairs from Europe (EMSCOT) and child/parent trios from North America (NCCCTS), we demonstrated that ocular and brain disease in congenital toxoplasmosis associate with polymorphisms in ABCA4 encoding ATP-binding cassette transporter, subfamily A, member 4 previously associated with juvenile onset retinal dystrophies including Stargardt's disease. Polymorphisms at COL2A1 encoding type II collagen, previously associated with Stickler syndrome, associated only with ocular disease in congenital toxoplasmosis. Experimental studies showed that both ABCA4 and COL2A1 show isoform-specific epigenetic modifications consistent with imprinting, which provided an explanation for the patterns of inheritance observed. These genetic and epigenetic risk factors provide unique insight into molecular pathways in the pathogenesis of disease.
Subject(s)
Female , Humans , Infant, Newborn , Pregnancy , ATP-Binding Cassette Transporters/genetics , Collagen Type II/genetics , Toxoplasmosis, Cerebral/genetics , Toxoplasmosis, Congenital/genetics , Toxoplasmosis, Ocular/genetics , Epigenesis, Genetic/genetics , Genotype , Polymorphism, Single NucleotideSubject(s)
Humans , Female , Pregnancy , Infant, Newborn , Antibodies , Clinical Laboratory Techniques , Immunoglobulins , Prenatal Diagnosis , Serologic Tests , Toxoplasmosis, Congenital/complications , Toxoplasmosis, Congenital/diagnosis , Toxoplasmosis, Congenital/epidemiology , Toxoplasmosis, Congenital/genetics , Toxoplasmosis, Congenital/immunology , Toxoplasmosis, Congenital/pathology , Toxoplasmosis, Congenital/prevention & control , Toxoplasmosis, Congenital/therapy , Toxoplasmosis, Congenital/transmission , Pregnancy Complications, Infectious/diagnosis , Fetus , Gestational Age , Infectious Disease Transmission, VerticalSubject(s)
Humans , Female , Pregnancy , Infant, Newborn , Allergy and Immunology , Antibodies , Fetus , Immunoglobulins , Infections/congenital , Infections/diagnosis , Infectious Disease Transmission, Vertical , Postnatal Care , Pregnancy , Prenatal Diagnosis , Serology , Toxoplasmosis, Congenital/diagnosis , Toxoplasmosis, Congenital/genetics , Toxoplasmosis, Congenital/pathology , Toxoplasmosis, Congenital/prevention & control , Toxoplasmosis, Congenital/therapy , Hydrocephalus , Prognosis , Risk , Spiramycin , UltrasonographyABSTRACT
En el presente trabajo se compararon los métodos de Hemaglutinación Indirecta (HAI) e Inmunoanálisis Enzimático (ELISA, IgM e IgG) para investigar anticuerpos antitoxoplasma en 54 muestras sanguíneas. Los resultados obtenidos muestran una concordancia del 62.96 por ciento entre HAI y ELISA. IgM y del 83.33 por ciento entre HAI y ELISA. IgG. El análisis estadístico mediante el chi cuadrado, reveló que hubo significancia cuando se compararon todos los títulos de HAI a partir de 1:2 con todos los índices de ELISA. IgM, esta significancia no puede establecer la superioridad de un método sobre el otro, debido: a. La utilización del "kit" comercial ELISA. IgM que solo detecta este tipo de anticuerpo; b. La detección por HAI de IgM e IgG; c. La presencia de anticuerpos inespecíficos de HAI y ELISA. IgG reveló que no hubo diferencias, lo cual nos indica que la discordancia entre ambos métodos no es estadísticamente significante