Risk of Death for Children with Down Syndrome and Sepsis

Garrison, Michelle M.; Jeffries, Howard E.; Christakis, Dimitri A.

doi:10.1016/j.jpeds.2005.06.032

Cited by 84 publications

(80 citation statements)

References 27 publications

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“…DS is associated with several complex clinical features including immunological abnormalities (4)(5)(6)(7)(8), and it has long been noticed that patients present abnormal thymuses, characterized by lymphocyte depletion, cortical atrophy, and loss of corticomedullary demarcation (9,10). In addition to higher susceptibility to infections-as evidenced during the H1N1 2009 pandemic where the likelihood of death was 300 times greater for DS patients (11)-DS is characterized by increased frequency of organ-specific autoimmune disorders and of lymphoid and myeloid leukemias, contrasting with a decreased risk for allergic diseases, particularly asthma (12,13).…”

mentioning

confidence: 99%

Decreased AIRE Expression and Global Thymic Hypofunction in Down Syndrome

Lima

Moreira-Filho

Ramos

et al. 2011

The Journal of Immunology

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The Down syndrome (DS) immune phenotype is characterized by thymus hypotrophy, higher propensity to organ-specific autoimmune disorders, and higher susceptibility to infections, among other features. Considering that AIRE (autoimmune regulator) is located on 21q22.3, we analyzed protein and gene expression in surgically removed thymuses from 14 DS patients with congenital heart defects, who were compared with 42 age-matched controls with heart anomaly as an isolated malformation. Immunohistochemistry revealed 70.48 ± 49.59 AIRE-positive cells/mm2 in DS versus 154.70 ± 61.16 AIRE-positive cells/mm2 in controls (p < 0.0001), and quantitative PCR as well as DNA microarray data confirmed those results. The number of FOXP3-positive cells/mm2 was equivalent in both groups. Thymus transcriptome analysis showed 407 genes significantly hypoexpressed in DS, most of which were related, according to network transcriptional analysis (FunNet), to cell division and to immunity. Immune response-related genes included those involved in 1) Ag processing and presentation (HLA-DQB1, HLA-DRB3, CD1A, CD1B, CD1C, ERAP) and 2) thymic T cell differentiation (IL2RG, RAG2, CD3D, CD3E, PRDX2, CDK6) and selection (SH2D1A, CD74). It is noteworthy that relevant AIRE-partner genes, such as TOP2A, LAMNB1, and NUP93, were found hypoexpressed in DNA microarrays and quantitative real-time PCR analyses. These findings on global thymic hypofunction in DS revealed molecular mechanisms underlying DS immune phenotype and strongly suggest that DS immune abnormalities are present since early development, rather than being a consequence of precocious aging, as widely hypothesized. Thus, DS should be considered as a non-monogenic primary immunodeficiency.

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confidence: 99%

Decreased AIRE Expression and Global Thymic Hypofunction in Down Syndrome

Lima

Moreira-Filho

Ramos

et al. 2011

The Journal of Immunology

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“…Garrison y cols. 8 comunicaron un 30% de incremento en el riesgo de mortalidad en la población infantil con SD comparado con niños sin SD. Esto se debe tanto a factores inmunológicos 20 como no inmunológicos 19 (tabla 2).…”

Section: Patología Infecciosaunclassified

“…Debe considerarse que los niños con SD presentan diferentes características en su inmunidad 8 , en la homeostasis redox 10 y neuroendocrinas, lo que origina distintos umbrales para el inicio y resolución de la falla orgánica, durante el desarrollo de la enfermedad crítica.…”

Section: Pronósticounclassified

“…A modo de ejemplo, en los pacientes con insuficiencia respiratoria que requieren de ventilación mecánica, los criterios para síndrome de distrés respiratorio agudo (SDRA) se presentan en forma más frecuente en niños con SD 7 . El riesgo de mortalidad por sepsis en estos pacientes aumenta un 30% tras corrección de factores de confusión 8 . Asimismo, las complicaciones respiratorias e infecciosas post-cardiocirugía son más comunes resultando en estadías más prolongadas en la unidad de cuidados intensivos (UCI) 9 .…”

Section: Introductionunclassified

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El niño con Síndrome de Down en la Unidad de Cuidados Intensivos

F¹,

F²,

B³

et al. 2017

Rev. chil. pediatr.

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“…En nuestro paciente existió concordancia entre el abordaje clínico y tratamiento ofrecido; sin embargo, se debe tomar en cuenta que los pacientes con síndrome de Down presentan 30% más riesgo de hospitalización por infecciones graves y mortalidad por septicemia que el resto de la población, 10 lo cual puede estar relacionado con anomalías del sistema inmune.…”

Section: Comentario Anatomopatológicounclassified