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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

Decreased AIRE Expression and Global Thymic Hypofunction in Down Syndrome

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Lima, Flavia A. [1] ; Moreira-Filho, Carlos A. [1] ; Ramos, Patricia L. [1] ; Brentani, Helena [2] ; Lima, Leandro de A. [3] ; Arrais, Magaly [4] ; Bento-de-Souza, Luiz C. [4] ; Bento-de-Souza, Luciana [4] ; Duarte, Maria I. [5] ; Coutinho, Antonio [6] ; Carneiro-Sampaio, Magda [1]
Total Authors: 11
[1] Univ Sao Paulo, Dept Pediat, Fac Med, BR-05403900 Sao Paulo - Brazil
[2] Univ Sao Paulo, Dept Psychiat, Fac Med, BR-05403900 Sao Paulo - Brazil
[3] Hosp Canc AC Camargo, BR-01509010 Sao Paulo - Brazil
[4] Hosp Coracao, BR-04004030 Sao Paulo - Brazil
[5] Univ Sao Paulo, Dept Pathol, Fac Med, BR-05403900 Sao Paulo - Brazil
[6] Inst Gulbenkian Ciencias, P-2781901 Oeiras - Portugal
Total Affiliations: 6
Document type: Journal article
Source: JOURNAL OF IMMUNOLOGY; v. 187, n. 6, p. 3422-3430, SEP 15 2011.
Web of Science Citations: 37

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/mm(2) in DS versus 154.70 +/- 61.16 AIRE-positive cells/mm(2) in controls (p < 0.0001), and quantitative PCR as well as DNA microarray data confirmed those results. The number of FOXP3-positive cells/mm(2) 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. The Journal of Immunology, 2011, 187: 3422-3430. (AU)

FAPESP's process: 05/56446-0 - High resolutions structural MRI and receptor imaging studies in refractory temporal lobe epilepsy: in vivo and ex vivo analyses
Grantee:Edson Amaro Junior
Support type: Inter-institutional Cooperation in Support of Brain Research (CINAPCE) - Thematic Grants