Mecanismos inflamatórios e imunológicos na síndrome de Down / Inflammatory and immunological mechanism in Downs syndrome

AUTOR(ES)
DATA DE PUBLICAÇÃO

2009

RESUMO

In recent years there has been an increase in life expectancy of individuals with Down´s syndrome (DS), with death causes differ from the general population. Some studies have shown that the immune response differs throughout life with changes related to aging. The RCAN1 gene (regulator of calcineurin type 1), located in the q22.12 region of chromosome 21 is described as responsible for the phenotype of DS. The gene RCAN1 inhibits the calcineurin activity, responsible for the dephosphorylation of the nuclear factor of activated T cells (NFAT), an essential step for the activation of the genes responsible for cytokines expression. The consequence is a possible reduction of the effector immune response. In adults with DS, the humoral and cellular immune responses have not been throughly investigated. Although the overexpression of the RCAN1 gene has already been described in many tissues, its expression in mononuclear cells of peripheral blood (PBMC) of adults with DS has not been evaluated. The objectives of this study were to evaluate aspects of humoral and cellular immune response, evaluate the quantitative expression of the RCAN1 gene and correlate the findings with the production of cytokines. The study group consisted of adults with Down´s syndrome (DS) with free trisomy karyotype (n = 24), a control group (CTR) composed of the mentally disabled of other etiologies (n = 21) and a group of healthy subjects (n = 8), as parameters for some experiments. The SD and CTR groups are followed in Associação de Pais e Amigos dos Excepcionais (APAE-SP). It was evaluated Hemogram and serology for detection of hepatitis B, cytomegalovirus, infectious mononucleosis, toxoplasmosis, rubella, measles, cRP, complement fraction C3, C4, antistreptolysin O and IgG, IgM and IgA immunoglobulin isotypes. The mononuclear cells were obtained by Ficoll-Hypaque gradient and the cells were cultured without stimuli, analyzed for the quantitative gene expression of RCAN1 and evaluated for immunophenotyping by flow cytometry. The culture supernatants were collected for measurement of cytokines IL-2, IL-4, IL-5, IL- 10, TNF and IFN.The results of this study showed that the frequency of positive tests for various infectious agents and other immunological parameters were comparable in both groups (DS and CTR). Immunophenotyping of individuals with DS showed an increase in NK cells, CD8 + lymphocytes, changes in CD4: CD8 ratio (1:1) and decreased B lymphocytes (CD19 +) when compared to the control group (p <0.05). The DS group had a spontaneous production of IFN, TNF and IL-10 higher than the CTR group (p<0.05). However, there was not any difference in RCAN1 gene expression (mRNA) between the two groups of the mentally disabled. The humoral and cellular immune profile in adults with Down´s syndrome from APAE-SP showed that there was no difference in the humoral aspects assessed in both groups (SD and CTR). For the cellular aspects, the immunophenotyping suggests a possible sign of premature aging of the immune system and the cytokine production show a proinflammatory profile. Nevertheless, this cytokines profile is not associated with level of expression of the RCAN1 gene.

ASSUNTO(S)

inflammation envelhecimento processos do sistema imunológico inflamação citocinas expressão gênica aging cytokines síndrome de down gene expression immune system processes down syndrome

ACESSO AO ARTIGO

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