Biomedical subjects

Alessandra Aquino

Publications and source records attributed to Alessandra Aquino.

8 recordsLinked to original sources

PubMed2006

The nACHR4 594C/T polymorphism in Alzheimer disease.

Alzheimer disease (AD) is the most common form of dementia with complex etiology and multifactorial origin. Although several neurochemical deficits have been described in AD patients, explanation of the nature of the cognitive disturbance is focused on the "cholinergic hypothesis." The neuronal nicotinic acetylcholine receptor (neuronal nAChR) belongs to the superfamily of ionic channel activated by ligand. This paper presents a population-based population association study, testing the hypothesis that variants of the nAChR gene confer genetic susceptibility to AD. The authors analyzed two cohorts constituted by 60 controls and 80 AD patients in which significant increase of 594T polymorphism in patients affected by AD versus controls was found. However, further studies are necessary to confirm this polymorphism trend and to establish the polymorphism functionality and its correlation with behavioral and cognitive deficit.

Aged↗

PubMed2006

Memory B cell subpopulations in the aged.

The literature on immunosenescence has focused mainly on T cell impairment. With the aim of gaining insight into B cell immunosenescence, the authors investigated the serum IgD levels in 24 young and 21 old people and analyzed their relationship with the number of CD19+CD27+ memory cells. Serum IgD were quantified by the use of radial immunodiffusion and the lymphocyte population CD19+CD27+ was identified by a FACScan flow cytometer. Serum IgD levels were significantly lower (p < 0.0001) in old subjects, and the percentage of CD19+CD27+ lymphocytes were significantly increased (p = 0.01) in old subjects. Finally, a significant negative correlation was found (p = 0.01) between serum concentrations of IgD and CD19+CD27+. The present results show that the levels of IgD are negatively age-related to the amount of B memory cells. This suggests that the B repertoire available to respond to new antigenic challenges is decreased in the elderly. In fact, many memory IgD- B cells fill immunologic space, and the number of naïve IgD+ B cells is dramatically decreased. Therefore, these preliminary results suggest that a decrease of naïve IgD+CD27- B cells and a concomitant increase of memory IgD-CD27+ B cells could represent hallmarks of B immunosenescence, might provide biomarkers related to the lifespan of humans, and could be useful for the evaluation of antiaging treatments.

Adult↗

PubMed2006

Inflammation, longevity, and cardiovascular diseases: role of polymorphisms of TLR4.

The total burden of infection at various sites may affect the progression of atherosclerosis, the risk being modulated by host genotype. The role of lipopolysaccaride receptor TLR4 is paradigmatic. It initiates the innate immune response against gram-negative bacteria; and TLR4 polymorphisms, as ASP299GLY, suggested to attenuate receptor signaling, have been described. We demonstrated that TLR4 ASP299GLY polymorphism shows a significantly lower frequency in patients affected by myocardial infarction compared to controls, whereas centenarians show a higher frequency. Thus, people genetically predisposed to developing weak inflammatory activity, seem to have fewer chances of developing cardiovascular diseases (CVD) and, subsequently, live longer if they do not become affected by serious infectious diseases. These results are in agreement with our other data demonstrating how genetic background may exert the opposite effect with respect to inflammatory components in CVD and longevity. In the present report, to validate this hypothesis, the levels of interleukin (IL)-6, a pro-inflammatory cytokine involved in atherosclerosis and longevity, were determined by an enzyme-linked immuno-sorbent assay (ELISA) in supernatants from a whole blood assay after stimulation with subliminal doses of lipopolysaccaride (LPS) from Escherichia coli (E. coli). The samples, genotyped for the ASP299GLY polymorphism, were challenged with LPS for 4, 24, and 48 h. What we found was that Il-6 values were significantly lower in carriers bearing TLR4 mutation. Therefore, the pathogen burden, by interacting with host genotype, determines the type and intensity of the immune-inflammatory responses accountable for pro-inflammatory status, CVD, and unsuccessful aging. On the other hand, our present data seem to explain the inconclusive results obtained in case-control studies taking into account the role of functional IL-6 polymorphisms in successful and unsuccessful aging. In fact, IL6 levels seem to depend, in addition, on IL-6 polymorphisms and on innate immunity gene polymorphisms as well.

Acute Disease↗

PubMed2004

Impairment of gamma/delta T lymphocytes in elderly: implications for immunosenescence.

Gamma/delta T lymphocytes cells recognize the antigen in a non-classical way and are considered the third branch of the immune system devoted to defend the integrity of the body. Ageing is characterized by an impairment of the main way of protection (the adaptive branch) but, successfully aged people show compensatory mechanisms of defense such as proneness to inflammation. Moreover, very old subjects show an increased number of NK cells. We have previously demonstrated that gamma delta T lymphocytes are reduced in elderly. In the present paper we have studied some characteristics of these cells to evaluate the possibility that these cells might balance the decreased action of the adaptive branch in successfully aged people. Cytofluorimetric analysis of cells collected from young, old and centenarian subjects has been used to evaluate the ability of these cells to expand in vitro. Here we demonstrate that gamma delta T cells are impaired in the ability to proliferate to different stimuli such as isopentenyl pyrophoshate, that select gamma delta T lymphocytes bearing delta 2 chain, other than to phytohemagglutinin and anti-CD3 that are polyclonal activators. Moreover, we demonstrate that gamma delta T cells in aged and centenarians show an enhanced sensitivity to undergo apoptosis induced both by alpha-Fas and TNF-alpha. All together these data suggest that gamma delta T lymphocytes are impaired in elderly and suggest that the reduced ability to proliferate and the reduced number of circulating gamma delta T lymphocytes is due to the proneness to apoptosis. Finally on the basis of these data, we conclude that gamma delta T lymphocytes, do not participate in the remodeling of the immune system due to the reduction of classical T cell response and replacement by NK cells in elderly.

Adult↗

PubMed2004

CD4+ CCR5+ and CD4+ CCR3+ lymphocyte subset and monocyte apoptosis in patients with acute visceral leishmaniasis.

The potential involvement of apoptosis in the pathogenesis of visceral leishmaniasis (VL) was examined by studying spontaneous and Leishmania antigen (LAg)-induced apoptosis using cryopreserved peripheral blood mononuclear cells (PBMC) of Sicilian patients with VL. Results indicate that monocytes and T lymphocytes from acute VL patients show a significantly higher level of apoptosis compared with that observed in healed subjects. The percentage of apoptotic cells was higher in monocytes than in T lymphocytes. T cells involved in programmed cell death (PCD) were mainly of the CD4(+) phenotype. In particular, the T helper 1-type (Th1) subset, as evaluated by chemokine receptor-5 (CCR5) expression, is involved in this process. Cell death in Th1-type uses a CD95-mediated mechanism. Furthermore, Th1-type CCR5(+) cells are prone to cell suicide in an autocrine or paracrine way, as attested by enhanced expression of CD95L in acute VL patients. The reduction in Th1-type cells by apoptosis was confirmed by the decrease in interferon-gamma secretion. In conclusion, apoptosis of monocytes, CD4(+) and CD4(+) CCR5(+) T cells could be involved in the failure of cell mediated immunity that is responsible for severe immune-depression in VL.

Acute Disease↗

PubMed2004

Looking for immunological risk genotypes.

Several functional markers of the immune system may be used either as markers of successful aging or conversely as markers of unsuccessful aging. Particularly, a combination of high CD8 and low CD4 and poor T cell proliferation has been associated with a higher two-year mortality in very old subjects. Therefore, genetic determinants of longevity should reside in those polymorphisms for the immune system genes that regulate immune responses. Concerning these changes in T cell subpopulations, how much they depend on the immunogenetic background and how much they depend on individual antigenic load, such as chronic infections, should be assessed. As previously demonstrated in our population, the interleukin (IL)-2 high-producer genotype is less frequent in old men than in young people; conversely, the IL-10 high-producer genotype is increased in old men. In this study, we tried to assess the role of low- and high-producer genotypes for IL-10 and IL-2 in the CD4 and CD8 absolute values, taking into account gender and age. The results suggest that old men carrying an anti-inflammatory IL-10 high-producer genotype or a proinflammatory IL-2 low-producer genotype show the lowest values of CD8 cells. Although in our study we were not able to show any correlation with CD4 values and no functional assessment of T cell was performed, these results suggest that cytokine genotypes may be involved in the subpopulation dynamics in old age.

Adult↗

PubMed2003

B cells in the aged: CD27, CD5, and CD40 expression.

Ageing is characterized by numerous changes in lymphocyte subpopulations. In the present paper we have focused on B cells carrying the surface markers CD27, CD5 and CD40. CD27 is considered a marker of primed (memory) cells and its engagement promotes the differentiation of memory B cells into plasma cells. CD5 is expressed on B1 cells, which are considered to be responsible for T cell-independent antibody production other than autoantibodies. The CD40 molecule binds CD40L (CD154) and is necessary for T-dependent antibody responses. Here we show that the absolute number of CD5+ and CD40+ B cells is decreased in the elderly, while CD27+ B lymphocytes only marginally decrease in centenarians. However, there is a decrease of the percentage of CD5+ B cells, an increase of CD27+ B cells, while CD40 does not change significantly. These data, together with the increased number of NK cells during aging, suggest different regulation of antibody production in the elderly which might be another example of immune remodeling with aging, based on interactions between human B and NK cells.

Adult↗

PubMedDate not supplied

Gamma/delta T lymphocytes are affected in the elderly.

gammadelta T lymphocytes are considered to represent a link between the inflammatory response and adaptive immunity. In the present paper we investigated whether these cells play any role in the remodeling of the immune system described in the elderly. We show that the absolute number of gammadelta T cells in peripheral blood of old and very old subjects is reduced. Moreover, gammadelta T cells from old people and centenarians show enhanced levels of the early activation marker CD69 both after culture in medium alone and in LPS-stimulated cells. Furthermore, they show a basal increased production of tumor necrosis factor (TNF)-alpha as evaluated at the single cell level. Additionally, the response of these cells to IPP in "in vitro" cultures is in part impaired. These results suggest that the high level of basal activation of gammadelta T cells is due to the "inflamed" environment. However, the changes in number and function of gammadelta T lymphocytes might influence the resolution of inflammatory immune responses in the elderly.

Adult↗