Please use this identifier to cite or link to this item: https://observatorio.fm.usp.br/handle/OPI/23301
Title: Decreased AIRE Expression and Global Thymic Hypofunction in Down Syndrome
Authors: LIMA, Flavia A.MOREIRA-FILHO, Carlos A.RAMOS, Patricia L.BRENTANI, HelenaLIMA, Leandro de A.ARRAIS, MagalyBENTO-DE-SOUZA, Luiz C.BENTO-DE-SOUZA, LucianaDUARTE, Maria I.COUTINHO, AntonioCARNEIRO-SAMPAIO, Magda
Citation: JOURNAL OF IMMUNOLOGY, v.187, n.6, p.3422-3430, 2011
Abstract: 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.
Appears in Collections:

Artigos e Materiais de Revistas Científicas - FM/MPE
Departamento de Pediatria - FM/MPE

Artigos e Materiais de Revistas Científicas - FM/MPS
Departamento de Psiquiatria - FM/MPS

Artigos e Materiais de Revistas Científicas - FM/MPT
Departamento de Patologia - FM/MPT

Artigos e Materiais de Revistas Científicas - LIM/06
LIM/06 - Laboratório de Imunopatologia da Esquistossomose e outras Parasitoses

Artigos e Materiais de Revistas Científicas - LIM/23
LIM/23 - Laboratório de Psicopatologia e Terapêutica Psiquiátrica

Artigos e Materiais de Revistas Científicas - LIM/36
LIM/36 - Laboratório de Pediatria Clínica


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