Intrinsic Abnormalities of Lymphocyte Counts in Children with Down Syndrome

Hingh, Yvette C.M. de; Vossen, P.; Gemen, Eugenie F.A.; Mulder, André B.; Hop, Wim C. J.; Brus, F; Vries, Esther de

doi:10.1016/j.jpeds.2005.07.022

Cited by 183 publications

(159 citation statements)

References 20 publications

(22 reference statements)

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“…High serum levels of IgG1 and IgG3 have been reported in DS adults (18). Despite their high IgG levels, DS children have been recently shown to present a lower number of B lymphocytes compared to controls throughout childhood (19).…”

Section: Discussionmentioning

confidence: 99%

Antibody response to pneumococcal capsular polysaccharide vaccine in Down syndrome patients

Costa‐Carvalho¹,

Martínez²,

Dias³

et al. 2006

Braz J Med Biol Res

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The majority of children with Down syndrome (DS) tend to have frequent bacterial infections including recurrent respiratory infections. Our objective was to evaluate the production of antibodies to pneumococcal polysaccharide antigens after active immunization in DS subjects. IgG antibodies to pneumococcal serotypes (1, 3, 6B, 9V, and 14) were measured before and 6 weeks after immunization with a 23-valent pneumococcal vaccine (Pneumo23 ® , Pasteur-Merrieux) in 6-to 13-year-old DS children (N = 17) and in aged-matched normal controls (N = 30). An adequate response was defined as a 4-fold increase over baseline or a post-immunization level of specific pneumococcal serotype antibody ≥1.3 µg/mL. After immunization, all DS children had an increase in post-immunization levels against all serotypes analyzed. A 4-fold or more increase was observed in all DS children concerning serotypes 1 and 14, in 90% of subjects for serotypes 3 and 9V, and in 65% for serotype 6B. Regarding this increase, 8 of the 17 DS children had an adequate response to all serotypes analyzed, 8/17 patients to 4 serotypes and 1/17 to 3 serotypes. However, when we compared post-immunization levels between DS children and controls, we observed lower levels in the former group (P < 0.05) for all serotypes except serotype 3. We conclude that pneumococcal polysaccharide immunization could be beneficial for these DS children.

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Section: Discussionmentioning

confidence: 99%

Antibody response to pneumococcal capsular polysaccharide vaccine in Down syndrome patients

Costa‐Carvalho¹,

Martínez²,

Dias³

et al. 2006

Braz J Med Biol Res

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“…Thus, the thymus in DS individuals had been reported to be smaller and hypocellular, even in infants, containing a decreased proportion of phenotypically mature TCR-ab + thymocytes (6). The number of TRECs and the size of T cell subpopulations (CD4 + , CD8 + , CD4 + CD45 + RA cells) in the peripheral blood of DS individuals have been described as reduced at various age groups (4,6,7). It was also demonstrated that DS patients present low naive T cell numbers (44).…”

Section: Impaired Thymic Function and Development In Dsmentioning

confidence: 99%

“…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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“…De esta manera los pacientes con SD son más susceptibles a infecciones del tracto respiratorio inferior, principalmente neumonía, las que motivan su hospitalización en UCI 5,16 . Esto es dado en parte a las particularidades en la anatomía de la vía aérea 17 , problemas derivados de la higiene oral 18 , hipotonía muscular, aspiración por trastorno de la deglución, y alteraciones en la inmunidad innata y adaptativa 19,20 .…”

Section: Patología Respiratoriaunclassified

“…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