0000000000119921
AUTHOR
Giuseppina Colonna Romano
HLA, aging, and longevity: a critical reappraisal.
Despite a large number of studies, available data do not allow at present to reach definitive and clear conclusions on role of HLA on longevity, owing to major methodological problems, such as serological and molecular typing of different loci, insufficient sample sizes, different inclusion criteria and age cut-off, inappropriate mixing of data referred to people from 58 to over 100 years of age, inappropriate control matching, and neglected consideration of sex-related effects and the different genetic make-up of studied populations. However, within this confused scenario, some data emerge. First, two studies that do not fit the biases above discussed show that some HLA alleles are associa…
Genetic Background of Centenarians May Be Protective Against Cardiovascular Diseases.
Age-related changes in the expression of CD95 (APO1/FAS) on blood lymphocytes☆
Abstract Aging is associated with alterations of the immune system, thought to be related to an increased susceptibility to infectious diseases, and possibly to cancer and autoimmunity in the elderly. In the present paper we report data obtained on freshly collected blood from 148 healthy subjects of different ages (from cord blood to 102 years old). The subjects were divided into seven age classes (cord blood, 3–11 years, 15–39 years, 41–60 years, 61–74 years, 75–84 years, 85–102 years) and their lymphocyte subsets and the expression of the apoptosis-related molecule CD95 were evaluated. In respect of lymphocyte subsets, the major differences were found in the cord-blood samples compared w…
La diagnosi di Laboratorio della malattia di Alzheimer: ruolo dei markers infiammatori.
Apoptosis and ageing.
Stimulation of T cells from aged individuals leads to different kinds and/or size of responses if compared with the responses of T cells obtained from young individuals. In fact elderly is associated with a progressive decline of immune response besides an increasing incidence of autoimmune phenomena. These differences might be the result of modified cellular mechanisms controlling the immune system in the course of ageing. The apoptotic deletion of activated T cells has been proposed as the key mechanism to maintain T cell homeostasis, and in this respect CD95 (Fas antigen) seems to play a major role in this course of events. In this study we show that just collected lymphocytes from old s…
Regulatory T cells and ageing
Studio longitudinale degli effetti della psicoterapia sulla funzionalità immunitaria in soggetti affetti da disturbo depressivo unipolare
Gruppi sanguigni e Sistema HLA
CD4+ / CCR5+ and CD4+ / CCR3+ lymphocyte subset and monocyte apoptosis in patients with acute visceral leishmaniasis
Frequenza dei polimorfismi del peptide segnale del TGF-b1 in un gruppo di pazienti affetti da stenosi carotidea
Vascular Aging effect on Medial aorta degeneration: focus on blood keukocyte telomere lenght in Hypertensive and old patients with sporadic thoracic aortic aneurysm
Polymorphisms of genes of TGF-beta pathway and susceptibility to colorectal cancer
Background: Genetic background implicated in cytokine network may have a key role in the susceptibility to colorectal cancer (CRC). The TGF-β pathway is involved in several biological processes, including cell proliferation, differentiation, migration and apoptosis. Methods: rs1800471 SNP polymorphism of TGF-ß1 rs334348 and rs334349 of TGF-βR1, rs900 of TGF-β2 and rs4522809 of TGF-β2R2 were typed in a group of 82 patients affected by sporadic CRC and in 237 age- and sex-matched healthy controls, using a competitive allele specific PCR assays (KASPar), developed by KBioscience (England). Results: No significant genetic contribution has been observed for 3 of the 5 SNPs tested. Indeed, a sign…
Bone marrow B lymphocytes in multiple myeloma and MGUS: Focus on distribution of naïve cells and memory subsets.
Multiple myeloma (MM) is caused by proliferation of clonal plasma cells (cPCs) in bone marrow (BM), associated with numerical and functional defects in immune subsets. An impairment of B cell compartment is involved in onset/progression of the disease.By flow cytometry, we studied distribution of naïve/transitional (IgD(+)CD27(-)), memory unswitched (IgD(+)CD27(+)), memory switched (IgD(-)CD27(+)) and double negative (DN) (IgD(-)CD27(-)) B lymphocytes in BM of control subjects, and responding and relapsing patients.We observed an increased percentage of IgD(+)CD27(+) B cells in healthy controls vs responding patients (p0.05). Treated non complete responders exhibited an expanded DN compartm…
B cells and immunosenescence: a focus on IgG+IgD-CD27- (DN) B cells in aged humans.
Immunosenescence contributes to the decreased ability of the elderly to control infectious diseases, which is also reflected in their generally poor response to new antigens and vaccination. It is known that the T cell branch of the immune system is impaired in the elderly mainly due to expansion of memory/effector cells that renders the immune system less able to respond to new antigens. B lymphocytes are also impaired in the elderly in terms of their response to new antigens. In this paper we review recent work on B cell immunosenescence focusing our attention on memory B cells and a subset of memory B cells (namely IgG(+)IgD(-)CD27(-)) that we have demonstrated is increased in healthy el…
Immunosenescenza e Inflammaging
With the descriptive term "immunosenescence" we classically define all those modifications, related to age, which cause reduced efficiency of immune responses with an increased risk of infectious diseases, which in the old age become the first cause of death, of autoimmune phenomena and, presumably, of tumors; all accompanied by a characteristic pro-inflammatory state.
Looking for immunological risk genotypes
TRafficking profile in naive and memory B cells in young and old subjects
Opposite role of CCR5 polymorphisms in cardiovascular diseases and longevity.
Immunological and immunogenetic markers in sporadic Alzheimer’s disease
Background: Common polymorphisms of genes controlling inflammation-modulating cytokines and acute-phase proteins which play important roles in the pathogenesis of Alzheimer''s disease (AD) have been shown to be associated with AD. Aims: The immunological and immunogenetic markers potentially useful for the AD risk evaluation and diagnosis are briefly reviewed. Conclusion: The state-of-the-art of immunological and immunogenetic markers of AD indicates that new tools and strategies are necessary to identify gene products useful as diagnostic tools.
The complex alteration in the network of IL-17-type cytokines in patients with hereditary angioedema
Hereditary angioedema (HAE) is a rare autosomic-dominant disorder characterized by a deficiency of C1 esterase inhibitor which causes episodic swellings of subcutaneous tissues, bowel walls and upper airways that are disabling and potentially life-threatening. We evaluated n = 17 patients with confirmed HAE diagnosis during attack and remission state and n = 19 healthy subjects. The samples were tested for a panel of IL (Interleukin)-17-type cytokines (IL-1β, IL-6, IL-10, granulocyte–macrophage colony stimulating factor (GM-CSF), IL-17, IL-21, IL-22, IL-23) and transforming growth factor-beta (TGF-β) subtypes. Data indicate that there are variations of cytokine levels in HAE subjects compar…
Study of the Association with -330T/G IL-2 in a Population of Centenarians from Centre and South Italy.
Immune response in elderly is characterised by a progressive loss of the ability to cope environmental stressors with a characteristic remodelling of cytokine network. One of the data constantly reported in literature is the decrease of IL-2 production. An IL-2 central role in the reconstitution of T cell function in vitro is largely documented. Studies on a T → G polymorphism at - 330 nt of IL-2 gene promoter region have demonstrated that T lymphocytes from 330GG homozygous subjects are able to produce in vitro higher amount of IL-2, than -330TG heterozygous or -330TT homozygous subjects. As a genetic background conditioning the maintaining of an efficient immune response would exert posit…
Linfociti
Frequency of polymorphisms of signal peptide of TGF-beta1 and -1082G/A SNP at the promoter region of Il-10 gene in patients with carotid stenosis
The role of inflammation in atherosclerosis is well recognized. We have evaluated the allele frequencies of the +869T/C and +915G/C polymorphisms (SNPs) at the TGF-beta1 gene and -1082G/A SNP at IL-10 promoter sequence, two well-known immunosuppressive and anti-inflammatory cytokines, in patients with carotid stenosis. Our data suggest a lack of association between these SNPs and the susceptibility to atherosclerosis although other reports have demonstrated this association. These results may be due to the pleiotropic effects of the cytokines and/or differences in haplotype combination that should be investigated to elucidate the role of TGF-beta1 and IL-10 polymorphisms in atherosclerosis.
Opposite role of pyrin M694V allele in acute myocardial infarction and longevity: results of a pilot study performed in Sicily.
Inflammation, longevity and cardiovascular diseases: role of polymorphisms of TLR4
Biomarkers of aging
Aging is a complex process that negatively impacts the development of the different systems and its ability to function. Moreover, the Aging rate in humans is not the same, principally due to genetic heterogeneity and environmental factors. The aging rate is measured as the decline of functional capacity and stress resistance. Therefore, several attempts have been made to analyse the individual age, ( so-called biological age) compared to chronological age. The biomarkers of aging are age-related body function or composition, these markers aim to assess the biological age and predict the onset of age-related diseases and/or residual lifetime. Such biomarkers should help in one hand to chara…
Immunogenetics of longevity. Is major histocompatibility complex polymorphism relevant to the control of human longevity? A review of literature data.
Literature data suggest that human longevity may be directly correlated with optimal functioning of the immune system. Therefore, it is likely that one of the genetic determinants of longevity resides in those polymorphisms for the immune system genes that regulate immune responses. Accordingly, studies performed on mice have suggested that the Major Histocompatibility Complex (MHC), known to control a variety of immune functions, is associated with the life span of the strains. In the last 25 years, a fair number of cross-sectional studies that searched for the role of HLA (the human MHC) genes on human longevity by comparing HLA antigen frequencies between groups of young and elderly pers…
Autoantibody production in aging: effect of cytokine gene polymorphisms in Sicilian ultra-nonagenarians
CITOCHINE. in: Compendio di Patologia generale (Caruso C. e Licastro F. eds.)
Antigeni, anticorpi, TCR
Associazione dei polimorfismi dei geni INF-γ ed IL-10 con la suscettibilità alla Febbre bottonosa.
TGF-B pathway polymorphisms as markers for gender differential susceptibility to sporadic thoracic aortic aneurysm
CD4+CD25+ regulatory cells in aged people are related to IL-10 genetic background and have effect on CMV-specific CD8 lymphocytes
IL-10 and TNF-α polymorphisms and the recovery from HCV infection
Hepatitis C virus (HCV) infection becomes chronic in about 85% of infected individuals, whereas only 15% of infected people clear spontaneously the virus. It is conceivable that the host immunogenetic background influences the course of infection in term of recovery. Thus, in this study we have evaluated the effect of functionally relevant polymorphisms at tumor necrosis factor-alpha (TNF-alpha, i.e., 2 biallelic polymorphisms at nt -863 and nt-308 of the promoter) and interleukin-10 (IL-10) loci (i.e., 1 biallelic polymorphism at nt -1082 of the promoter), on the clearance of HCV infection. To this purpose, we compared 18 Sicilian patients who had spontaneously recovered from previous HCV …
Le cellule T regolatrici CD4+CD25+ negli anziani sono correlate al background genetico dell’Il-10 ed hanno effetti sui linfociti CD8-CMV specifici
ATHEROSCLEROSIS in: Cytokine gene polymorphisms in multifactorial conditions (K. Vandenbroeck ed.)
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) expres…
Longevity in: Cytokine Gene Polymorphisms in multifactorial conditions. (K. Vandenbroeck ed.)
Ruolo delle mutazioni del gene della febbre mediterranea familiare nel raggiungimento dell’invecchiamento con successo.
Granulocyte and natural killer activity in the elderly
The deterioration of the immune system in ageing, 'immunosenescence', is thought to contribute to increased morbidity and mortality from infections and possibly autoimmune diseases and cancer. The most profound changes involve effector and immunoregulatory T-cell functions. Immunosenescence appears also to be related to changes in non specific immunity as well. In the present study we have assessed superoxide production, chemotaxis and the expression of the apoptosis-related molecule APO1/Fas (CD95) on neutrophils (PMN) from young and old subjects. Furthermore, we have measured the basal natural killer (NK) activity of young and elderly subjects and we have compared the number of CD16+ cell…
Familial mediterranean fever, longevity and cardiovascular diseases: a pilot study in the Sicilian population
Opposite role of pro-inflammatory alleles in longevity and atherosclerosis: results of studies performed in male centenarians and male myocardial infarcion patients from Sicily
FREQUENZA DEGLI ALLELI DEL POLIMORFISMO -330T-->G IL-2 IN UNA POPOLAZIONE DI CENTENARI ITALIANI
Sottopopolazioni linfocitarie in soggetti affetti da disturbo depressivo unipolare
HLA-B8,DR3 haplotype affects lymphocyte blood levels
The number of lymphocytes in the blood is constant, pointing to an effective control of circulating lymphocyte values. The mechanisms of this regulation are uncertain, although it is likely that the number of blood lymphocytes is conditioned by hormones, homing factors and cytokines whose production is at least partly restrained by genetic factors. Particularly genetic factors linked to major histocompatibility complex (MHC) appear to be involved. In human beings a decreased number of blood lymphocytes has been described in healthy subjects carrying the Human Leucocyte Antigens (HLA) haplotype HLA-B8,DR3. In the present study, to inquire into the mechanisms of this lymphocyte decreased numb…
CITOCHINE
Cross-talk between Vβ8+and γδ+T lymphocytes in contact sensitivity
We have previously reported that T lymphocytes proliferating in vitro to the hapten trinitrochlorobenzene (TNCB) exhibit a very restricted V beta gene usage and response to TNCB is limited to T-cell receptors (TCR) composed of V beta 8.2 in combination with V alpha 3.2, V alpha 8 and V alpha 10. This paper investigates the role played by T lymphocytes expressing the V beta 8.2 gene segment in the contact sensitivity (CS) reaction to TNCB in the intact mouse and in its passive transfer into naive recipient mice. Mice injected with monoclonal antibodies to V beta 8 are unable to develop CS upon immunization with TNCB and 4-day TNCB-immune lymph node cells from mice that had been depleted in v…
Association between +1059G/C CRP polymorphism and acute myocardial infarction in a cohort of patients from Sicily: a pilot study.
Immune-inflammatory responses in successful and unsuccessful ageing
A dramatic increase in mean life span and life expectancy, coupled with a significant reduction in early mortality, has lead to a large increase in number of elderly people in modern societies. This demographic phenomenon has been paralleled by an epidemic of chronic diseases associated with advancing age. Both innate and instructive immunity are implicated in almost all age-related diseases. The modifications of the immune system in the elderly are evaluated as a deterioration of the immune system, the so-called immunosenescence, which is thought to be mostly the result of the declining effectiveness of T cells and it is responsible for the increased susceptibility of elderly to infectious…
Upregulation of cytokines and IL-17 in patients with hereditary angioedema
A genetically determined high setting of TNF-alpha influences immunologic parameters of HLA-B8,DR3 positive subjects: implications for autoimmunity.
The 8.1 ancestral haplotype (AH) is a common Caucasoid haplotype carried by most people who type for HLA-B8,DR3. It seems unique in its association with a wide range of immunopathologic diseases. Healthy subjects bearing this haplotype demonstrate several alterations of immune response. This article will focus on the identification of the mechanism(s) of disease susceptibility of 8.1 AH. In 13 carriers of 8.1 AH, and 43 negative patients, enzyme immune assays serum levels of tumor necrosis factor (TNF)-alpha, soluble endothelial leukocyte adhesion molecule-1 (sELAM-1), cortisol, and interleukin(IL)-10 were determined. In addition, quantification of cytokine produced in vitro after mitogen s…
Frequency of polymorphisms of signal peptide of TGF-β1 and –1082G/A SNP at the promoter region of IL-10 gene in a group of patients with carotid stenosis.
Age at onset of Alzheimer disease and Tumor Necrosis Factor-Alpha -308A/G Polymorphism. Alzheimer’s and Parkinson diseases:
Pathogenesis of autoimmune diseases associated with 8.1 ancestral haplotype: effect of multiple gene interactions.
Genetic studies have shown that individuals with certain HLA alleles have a higher risk of specific autoimmune disease than those without these alleles. Particularly, the association in all Caucasian populations of an impressive number of autoimmune diseases with genes from the HLA-B8,DR3 haplotype that is part of the ancestral haplotype (AH) 8.1 HLA-A1, Cw7, B8, TNFAB*a2b3, TNFN*S, C2*C, Bf*s, C4A*Q0, C4B*1, DRB1*0301, DRB3*0101, DQA1*0501, DQB1*0201 has been reported by different research groups. This haplotype, the more common one in northern Europe, is also associated in healthy subjects with a number of immune system dysfunctions. It has been proposed that a small number of genes withi…
Carcinoembryonic Antigen as a Monitor in Breast Cancer
: Carcinoembryonic antigen (CEA) levels were serially determined in 125 patients with breast cancer in order to study the diagnostic and prognostic use of serum CEA levels before and/or after surgery and during treatment with hormonal and chemotherapy. Serum CEA levels were elevated in 15.5% of nonmetastatic patients. Carcinoembryonic antigen increased according to stage (TNM classification); and a direct relationship between positive CEA levels and subsequent recurrence was found. After a three-year postoperative interval a 50% survival rate was exhibited in CEA-positive patients vs an 88% survival rate in those patients found to be CEA negative. There is a definite correlation between the…
Age-related Diseases: Key Role of Insulin Resistance for the Association Between Type II Diabetes and Alzheimer’s Disease
Background: Alzheimer’s disease (AD) and Type 2 diabetes mellitus (T2DM) present many relationships. Insulin resistance (IR) plays a key role in neuronal degeneration and death. Reduced energy makes neurons more sensible to oxidation causing mitochondrial damages. Moreover AD brain has lower insulin utilization, reduced expression of its receptors and of IGF 1 and 2, all necessary for neuronal survival and learning and memory processes. Hyperinsulinemia is correlated with increase of hyerphosphorilated tau-protein. SHIP2, a phosphatase, is an antagonist of PI3K. Since the PI3K plays a key role in the biological effects of insulin, its attenuation could be associated with IR in T2DM. Methods…
Linkage of HFE with HLA antigens: a study in Sicilian population.
Genetics, gender and longevity
Correlation between CD117+ myeloma plasma cells and hematopoietic progenitor cells in different categories of patients
Background Multiple myeloma (MM) is a neoplastic disorder of plasma cells interesting mainly the elderly. MM remains an incurable disease, mostly because of the strong interplay between clonal plasma cells (cPCs) and bone marrow (BM) microenvironment. Multiparameter flow cytometry (MFC) allows the simultaneous study of the cPC immunophenotype and alterations involving other cells in BM, but rarely these data are interpreted as connected. One exception to this habit are previous studies about relationship between CD117 cPC positivity and hematopoietic progenitor cell (HPC) distribution in newly diagnosed patients. Thus we were interested in verifying the distribution of BM CD34+ HPCs in heal…
In vitro reactivity of peripheral blood mononuclear cells from subjects with different genetic background to amyloid b (Ab42) peptide: implication for cancer an immunotherapy.
Sphincter-like motion following machanical dilation of the internal inguinal ring during indirect inguinal hernia procedure
INTRODUCTION: Even today, there is still great speculation as to the underlying pathogenesis of inguinal hernia. As a result, it could be extrapolated that the vast majority of repairs are based upon conjecture. Most current repairs are founded upon the principle of "closing the defect" in the anatomy, either by suturing closed under tension, covering with a mesh or obliterating the defect with a plug. Many variants of each method are refined to achieve better clinical outcomes. Yet few, if any, strive to understand a fundamental question: "What has gone wrong with the normal physiological and anatomical mechanisms that prevent abdominal structures protruding through the abdominal wall?" We…
Apoptosi dei subsets linfocitari CD4+/ CCR5+, CD4+/ CCR3+ e dei monociti in pazienti con leishmaniasi viscerale acuta
La ligature terminale des branches de l’artère thyroïdienne inférieure diminue la morbidité parathyroïdienne après thyroïdectomie totale pour goitre
Resume But de l’etude Le but de cette etude etait d’evaluer l’impact de la ligature proximale de l’artere thyroidienne inferieure sur le taux postoperatoire de calcium et de parathormone chez les patients operes d’une thyroidectomie totale pour goitre. Patients et methodes Une etude randomisee a compare un groupe de patients operes par ligature proximale tronculaire de l’artere thyroidienne inferieure (groupe 1) a un deuxieme groupe de patients operes par ligature distale des branches de l’artere thyroidienne inferieure au contact de la capsule thyroidienne. Cent vingt-six patients consecutifs operes d’une thyroidectomie totale pour goitre multiheteronodulaire euthyroidien ont ete inclus. S…
Old and new immunophenotypic markers in multiple myeloma for discrimination of responding and relapsing patients: The importance of “normal” residual plasma cell analysis
Background Multiple myeloma is an incurable disease characterized by proliferation of clonal malignant plasma cells (CPCs), which can be immunophenotypically distinguished from polyclonal plasma cells (PPCs) by multiparameter flow cytometry (MFC). The utility of PPCs analysis in detecting prognostic and predictive information is still a matter of debate. Methods: we tested the ability of 11 MFC markers in detecting differences in the immunophenotype of CPCs and PPCs among patients in various disease stages; we verified if these markers could be associated with disease stage/response to therapy despite the role of clinical parameters. Results: significant changes in the expression of markers…
Pathophysiological implications of inflammation and genetic inflammatory factors in hypertensive and old patients affected by sporadic thoracic aortic aneurysm
Early activation of γδ T lymphocytes in the elderly
T cell function is altered in vivo and in vitro in elderly compared with young subjects, and this alteration is believed to contribute to morbidity and mortality in man due to the greater incidence of infection, as well as autoimmunity and cancer in elderly. The majority of T cells express TCRalphabeta whereas TCRgammadelta is expressed on a minority of T cells. Moreover, it is known that gammadelta T lymphocytes display major histocompatibility complex (MHC)- unrestricted cytotoxicity that is reminiscent of natural killer (NK) activity. In view of earlier findings on both T cells and NK cells in the elderly, we hypothesised a different behaviour of gammadelta T lymphocytes from old subject…