Inmunodeficiencia combinada severa (SCID) en Neiva, Colombia. Reporte de caso / Severe combined immunodeficiency (SCID) in Neiva, Colombia: Case Report

Resumen Introducción. Las inmunodeficiencias primarias son enfermedades genéticas del sistema inmune que incrementan la susceptibilidad a infecciones. Una de las formas más graves en niños es la inmunodeficiencia combinada severa. Presentación del caso. Se presenta el caso de un niño que fue diagnosticado con inmunodeficiencia combinada severa; este era un paciente masculino de ocho meses que presentó cuadro clínico consistente en múltiples hospitalizaciones debido a infección por citomegalovirus, endocarditis por Candida albicans e infección recurrente de las vías urinarias por Pseudomonas aeruginosa. El perfil inmunológico mostró disminución del número absoluto de células CD3+ y CD19+, lo que permitió realizar el diagnóstico de inmunodeficiencia combinada severa instaurándose manejo; sin embargo, el niño no se recuperó y falleció. Conclusiones. Las inmunodeficiencias primarias son patologías que requieren una intervención oportuna que permita brindar un mejor pronóstico a los pacientes.

Abstract Introduction: Primary immunodeficiencies are genetic disorders of the immune system that increase susceptibility to infections. One of the most serious forms in children is severe combined immunodeficiency. Case presentation: This is the report of the case of an 8-monthold male patient who was diagnosed with severe combined immunodeficiency. The child presented a clinical profile consisting of multiple hospitalizations due to cytomegalovirus infection, endocarditis by Candida albicans and recurrent urinary tract infection by Pseudomonas aeruginosa. The immune profile showed a decrease in the absolute number of CD3+ and CD19+ cells, which led to the diagnosis of severe combined immunodeficiency. Even though management was established, the child did not recover and died. Conclusions: The primary immunodeficiencies are disorders that require timely intervention to provide a better prognosis to patients.

Single-Nucleotide Polymorphisms in NOD1, RIPK2, MICB, PLCE1, TNF, and IKBKE Genes Associated with Symptomatic Dengue in Children from Colombia.

Functional immunological evidence supports the impact that the host genetic variability has on the susceptibility to develop asymptomatic or symptomatic dengue infection. Children are more prone to develop severe dengue. Thus, we have evaluated possible associations between single-nucleotide polymorphisms (SNPs) located in immune genes and the development of symptomatic dengue in children from two Colombian populations with differences in genetic backgrounds and geographical features. We genotyped 15 SNPs (in 12 genes) in 298 symptomatic children and 648 healthy controls. Ancestry proportions (APs) were inferred by genotyping 29 ancestry informative markers. We observed four SNPs associated with susceptibility to develop dengue in NOD1, RIPK2, MICB, or PLCE1 genes. Conversely, we found one SNP in TNF gene and two haplotypes in the IKBKE gene associated with resistance to develop dengue. These associations were adjusted by gender, APs, and the population of origin because the association of polymorphisms may be different in admixed populations like Colombian. To our knowledge, this is the first reported association study with dengue in IKBKE, RIPK2, and NOD1 genes. We have also confirmed previously reported associations in MICB and PLCE1 genes with dengue. Overall, our results contribute to the understanding of the genetic susceptibility/resistance to develop symptomatic dengue. Nevertheless, these associations must be validated through functional analysis.

Análisis descriptivo del compromiso de órganos en niños con dengue grave en Neiva, Colombia / Descriptive analysis of organ involvement in children with severe dengue in Neiva, Colombia

Resumen Introducción. La infección por dengue puede comprometer órganos como el miocardio y el hígado. Tal hecho puede agravar la evolución clínica, por ello estos órganos han sido considerados en la clasificación revisada de la Organización Mundial de la Salud (OMS) para esta enfermedad. Objetivo. Describir la presencia de afectación por dengue en órganos como miocardio, hígado y sistema nervioso central (SNC) en niños de Neiva, Colombia Materiales y métodos. Este estudio analizó 930 niños con diagnóstico de dengue confirmado que ingresaron al Hospital Universitario Hernando Moncaleano Perdomo de Neiva entre enero de 2009 y diciembre de 2010. Para el diagnóstico y estratificación clínica se usó la clasificación revisada de la OMS. La infección por dengue se confirmó por detección plasmática de NS1 o IgM específica. Se realizó seguimiento clínico y paraclínico diario durante toda la hospitalización. Resultados. De los 930 niños, 105 fueron clasificados como dengue grave (DG) y, de estos, 19 presentaron órganos afectados. El miocardio fue el más comprometido (14 casos), seguido por el hígado (4 casos) y el SNC (1 caso). Conclusión. El compromiso clínico del miocardio, el hígado o el SNC se observó en el 18% de los casos de niños con DG. Es necesario un diagnóstico y tratamiento oportuno de esta patología en niños.

Abstract Introduction: Dengue can compromise organs such as the myocardium and the liver. Clinical evolution may be aggravated by this fact, and for that reason, these organs have been considered in the revised classification of the World Health Organization (WHO) for this disease. Objective: To describe the affectation caused by dengue in organs such as the myocardium, the liver and the central nervous system (CNS) in children from Neiva, Colombia. Materials and methods: This study analyzed 930 children diagnosed with confirmed dengue and admitted to the Hernando Moncaleano Perdomo University Hospital of Neiva between January 2009 and December 2010. Diagnosis and clinical stratification were obtained based on the revised WHO classification. Dengue infection was confirmed by NS1 or specific IgM plasma detection. Daily clinical and paraclinical follow-up was performed during the full length of hospital stay. Results: Out of 930 children, 105 were classified as severe dengue (SD) and, of these, 19 had affected organs. The myocardium was the most compromised organ (14 cases), followed by the liver (4 cases) and the CNS (1 case). Conclusion: Clinical involvement of the myocardium, liver or CNS was observed in 18% of the cases of children with SD. A timely diagnosis and treatment of this pathology in children is necessary.

Characterization of rotavirus specific B cells and their relation with serological memory.

We quantified circulating total, rotavirus (RV) and Tetanus toxin (TT) memory B cells (mBc) in healthy adults using a limiting dilution assay (LDA) and a flow cytometry assay (FCA) that permit evaluation of both CD27+ and CD27- mBc. RV mBc were enriched in the CD27-, IgG+ and in the CD27+, IgM+ subsets. The numbers of RV mBc were higher by FCA than by LDA and results of the two assays did not correlate. TT IgGmBc and RV IgA mBc determined by FCA and by LDA correlated with TT plasma IgG and RV plasma IgA, respectively. The mean ratio of specific mBc/mug/ml of the corresponding plasma immunoglobulin was lower for TT IgG than for RV IgA mBc. Our studies contribute to understand the relationship between circulating mBc and serological memory, and enhance our capacity to develop better correlates of protection against RV disease.

Evaluation of circulating intestinally committed memory B cells in children vaccinated with attenuated human rotavirus vaccine.

In a double blind trial, 319 fully immunized children received two doses of either placebo or 10(6.7) focus-forming units of the attenuated RIX4414 human rotavirus (RV) vaccine ("all-in-one" formulation). Plasma RV-specific IgA (RV IgA), stool RV IgA, and circulating total and RV memory B cells (CD19+ IgD+/- CD27+) with an intestinal homing phenotype (alpha4beta7+ CCR9+/-) were measured, after the first and second doses, as potential correlates of protection. After the first and/or second dose, 54% of vaccinees and 13% of placebo recipients had plasma RV IgA. Before vaccination, most (95%) of the children (of both study groups) were breast-fed and had stool RV IgA (68.64%). Coproconversion (4-fold increase) after the first and/or second dose was observed in 32.7% of vaccinees and 17.4% of placebo recipients. No significant difference was seen when comparing the frequencies of any subset of memory B cells between vaccinees and placebo recipients. Statistically significant weak correlations were found between plasma RV IgA titers and coproconversion, and several subsets of memory B cells. The vaccine provided 74.8% protection (95% confidence interval, 30.93-92.62) against any RV gastroenteritis and 100% protection (95% confidence interval, 14.53-100) against severe RV gastroenteritis. When vaccinees and placebo recipients were considered together, a correlation was found between protection from disease and plasma RV IgA measured after dose 2 and RV memory (IgD- CD27+ alpha4beta7+ CCR9+) circulating B cells measured after dose 1. However, the correlation coefficients for both tests were low (<0.2), suggesting that other factors are important in explaining protection from disease.