MGUS and multiple myeloma: looking for “new” markers and exploring the interaction with the bone marrow microenvironment.

Utility of CD54, CD229, and CD319 for the identification of plasma cells in patients with clonal plasma cell diseases

Background Multiparameter flow cytometry (MFC) identification and characterization of plasma cells (PCs) is a useful tool to support diagnosis, prognostication, and monitoring of PC diseases (PCD). Currently, the number of MFC markers suited for the identification of PC remains limited. Moreover, antibody therapies against PC-associated markers further compromise the utility of the most widely used reagents (e.g., CD38). Despite markers other than CD38 and CD138 are recognized as potentially useful PC-identification markers, no study has comparatively evaluated their performance in combination with CD38 and CD138. Here we compared the utility of CD229, CD54, and CD319 for the identification…

Effects of Oleuropein and Hydroxytyrosol on Inflammatory Mediators: Consequences on Inflammaging

Aging is associated with a low-grade, systemic inflammatory state defined as “inflammaging”, ruled by the loss of proper regulation of the immune system leading to the accumulation of pro-inflammatory mediators. Such a condition is closely connected to an increased risk of developing chronic diseases. A number of studies demonstrate that olive oil phenolic compound oleuropein and its derivative hydroxytyrosol contribute to modulating tissue inflammation and oxidative stress, thus becoming attractive potential candidates to be used in the context of nutraceutical interventions, in order to ameliorate systemic inflammation in aging subjects. In this review, we aim to summarize the available d…

Targeting multiple myeloma with natural polyphenols

Multiple myeloma (MM) is still an incurable hematologic malignancy. Although new therapeutic strategies have been developed to target different pathways in malignant cells, such as proliferation, differentiation, and apoptosis, better survival rates have also been achieved by the introduction of autologous stem cell transplantation (ASCT). Hematopoietic stem cell transplantation and novel targeted agents, such as proteasome inhibitors, monoclonal antibodies, immunomodulatory drugs, check-point inhibitors and epigenetic modulators, have significantly achieved long remission time and increased survival rates. However, most patients relapse, develop resistance, and eventually die because of re…

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…

How Can We Improve Vaccination Response in Old People? Part I: Targeting Immunosenescence of Innate Immunity Cells

Vaccination, being able to prevent millions of cases of infectious diseases around the world every year, is the most effective medical intervention ever introduced. However, immunosenescence makes vaccines less effective in providing protection to older people. Although most studies explain that this is mainly due to the immunosenescence of T and B cells, the immunosenescence of innate immunity can also be a significant contributing factor. Alterations in function, number, subset, and distribution of blood neutrophils, monocytes, and natural killer and dendritic cells are detected in aging, thus potentially reducing the efficacy of vaccines in older individuals. In this paper, we focus on t…

Healthy ageing and Mediterranean diet: A focus on hormetic phytochemicals

Abstract Mediterranean diet (MedDiet) is rich in fruits and vegetables associated with longevity and a reduced risk of several age-related diseases. It is demonstrated that phytochemicals in these plant products enhance the positive effects of MedDiet by acting on the inflammatory state and reducing oxidative stress. Evidence support that these natural compounds act as hormetins, triggering one or more adaptive stress-response pathways at low doses. Activated stress-response pathways increase the expression of cytoprotective proteins and multiple genes that act as lifespan regulators, essential for the ageing process. In these ways, the hormetic response by phytochemicals such as resveratro…

Determinants of inappropriate hospitalization in cataract surgery in the south of Italy: a retrospective study

Purpose To analyze the frequency of inappropriate hospitalization in cataract surgery and the type of related determinants. Methods A nested retrospective case–control study was carried out on 2708 consecutive cataract surgery patients operated between January 2013 and Decem- ber 2015. All cases with inappropriate hospitalization (day surgery or ordinary hospitalization) were com- pared with a control group of cases treated in an appropriate (day service) regimen. The predictive value for inappropriate admissions to the hospital was assessed using a logistic regression model. Significant variables from the univariate analysis were included in a multivariate model. Results Forty-five cases (…

The impact of polypharmacy and drug interactions among the elderly population in Western Sicily, Italy.

Aim: Primary endpoint was to report polypharmacy distribution in the general population vs ≥65 years old people and to examine the frequency of drug–drug interactions (DDIs) in the Health Local Unit of Palermo, Italy, in relationship with patients’ age. Methods: Drug prescription data for the year 2014 were extracted from the database of the Local Health Unit of Palermo Province, Italy. Patients were divided into five age groups (0–13, 14–64, 65–69, 70–74, and ≥75 year old). The detection of potential DDIs in polypharmacy profiles was performed with NavFarma software (Infologic srl, Padova, Italia), with DDI classification provided by tool Micromedex Drug Reax (Truven Health Analitics, Mich…

The role of immunogenetics in covid‐19

Coronavirus disease 2019 (COVID-19) is induced by SARS-CoV-2 and may arise as a variety of clinical manifestations, ranging from an asymptomatic condition to a life-threatening disease associated with cytokine storm, multiorgan and respiratory failure. The molecular mechanism behind such variability is still under investigation. Several pieces of experimental evidence suggest that genetic variants influencing the onset, maintenance and resolution of the immune response may be fundamental in predicting the evolution of the disease. The identification of genetic variants behind immune system reactivity and function in COVID-19 may help in the elaboration of personalized therapeutic strategies…

USO DEI PARAMETRI POSIZIONALI E DELL’ANALISI CITOMETRICA MULTIPARAMETRICA PER IDENTIFICARE I CASI DI LEUCEMIA LINFATICA CRONICA

COMPARATIVE EVALUATION OF CD229, CD319 AND CD54 FOR FLOW CYTOMETRIC IDENTIFICATION OF BONE MARROW NORMAL/REACTIVE AND CLONAL/ABERRANT PLASMA CELLS

Immunopathology and Immunosenescence, the Immunological Key Words of Severe COVID-19. Is There a Role for Stem Cell Transplantation?

The outcomes of Coronavirus disease-2019 (COVID-19) vary depending on the age, health status and sex of an individual, ranging from asymptomatic to lethal. From an immunologic viewpoint, the final severe lung damage observed in COVID-19 should be caused by cytokine storm, driven mainly by interleukin-6 and other pro-inflammatory cytokines. However, which immunopathogenic status precedes this “cytokine storm” and why the male older population is more severely affected, are currently unanswered questions. The aging of the immune system, i.e., immunosenescence, closely associated with a low-grade inflammatory status called “inflammageing,” should play a key role. The remodeling of both innate …

HPV vaccine hesitancy among parents of female adolescents: a pre-post interventional study

Human papillomavirus (HPV) is the most common sexually transmitted infection in female adolescents. The highest infection rate is found among individuals aged 15-24 years, and the HPV vaccine represents an opportunity to reduce the burden of cervical cancer caused by HPV types 16 and 18. The World Health Organization has defined girls aged 9e13 years as the priority target for HPV vaccination. In Italy, in accordance with international public health guidelines, HPV vaccination wasfree and actively offered to all girls during their 12th year of life (from the completion of 11 years until the age of 12 years) between 2007 and 2008, establishing a target vaccination coverage of 95% within 5 ye…

How Can We Improve the Vaccination Response in Older People? Part II: Targeting Immunosenescence of Adaptive Immunity Cells.

The number of people that are 65 years old or older has been increasing due to the improvement in medicine and public health. However, this trend is not accompanied by an increase in quality of life, and this population is vulnerable to most illnesses, especially to infectious diseases. Vaccination is the best strategy to prevent this fact, but older people present a less efficient response, as their immune system is weaker due mainly to a phenomenon known as immunosenescence. The adaptive immune system is constituted by two types of lymphocytes, T and B cells, and the function and fitness of these cell populations are affected during ageing. Here, we review the impact of ageing on T and B …

Trends of influenza B during the 2010–2016 seasons in 2 regions of north and south Italy: The impact of the vaccine mismatch on influenza immunisation strategy

Influenza A and B viruses are responsible for respiratory infections, representing globally seasonal threats to human health. The 2 viral types often co-circulate and influenza B plays an important role in the spread of infection. A 6-year retrospective surveillance study was conducted between 2010 and 2016 in 2 large administrative regions of Italy, located in the north (Liguria) and in the south (Sicily) of the country, to describe the burden and epidemiology of both B/Victoria and B/Yamagata lineages in different healthcare settings. Influenza B viruses were detected in 5 of 6 seasonal outbreaks, exceeding influenza A during the season 2012–2013. Most of influenza B infections were found…

Sindrome di di Crigler-Najjar tipo 2: due nuove mutazioni missense nel gene UGT1A1.

La sindrome di Crigler-Najjar (CNS) è una malattia molto rara (prevalenza 1/1.000.000 nati) a trasmissione autosomica recessiva, caratterizzata da un incremento cronico e grave di bilirubina sierica indiretta (non coniugata), dovuta alla parziale (tipo 2) o completa (tipo 1) assenza funzionale dell’enzima epatico glucoronosil transferasi UGT1. La malattia si manifesta in età neonatale con un ittero precoce e intenso, dovuto alla presenza di bilirubina non coniugata e l'esame fisico è nella norma; in epoca di sviluppo gli effetti clinici della CNS tipo 1 sono letali in quanto l’eccesso di bilirubina porta inevitabilmente ad una encefalopatia essendo tale pigmento fortemente liposolubile. Le …

USE OF CELL POSITIONAL DATA AND MULTIPARAMETER FLOW CYTOMETRY TO IDENTIFY B CELL CHRONIC LYMPHOCYTIC LEUKAEMIA

Survey on energy drink consumption among the adult population in sicily: Do new drinking habits associate with the risk of alcoholism in the Crib of Mediterranean Diet?

Background: The market for and the level of energy drinks (EDs) consumption are increasing every year, and while only a few have a comprehensive knowledge about the potential harmful physiological and psychological effects of EDs, the number of publications that have documented the potential adverse risks associated with the use of these beverages remains small. Objectives: The present study aim to evaluate the prevalence of EDs consumers among the adult population and to verify the factors associated with its consumption and onset of adverse events. Patients and Methods: A cross-sectional survey was conducted using a knowledge, attitudes, and practices (KAP) semi-structured questionnaire, …

Anti-Inflammatory Effects of Nutritionally Relevant Concentrations of Oleuropein and Hydroxytyrosol on Peripheral Blood Mononuclear Cells: An Age-Related Analysis

: Immunosenescence and inflammaging facilitate the insurgence of chronic diseases. The Mediterranean diet is a non-invasive intervention to improve the chronic low-grade inflammatory status associated with aging. Olive oil oleuropein (OLE) and hydroxytyrosol (HT) demonstrated a controversial modulatory action on inflammation in vitro when tested at concentrations exceeding those detectable in human plasma. We studied the potential anti-inflammatory effects of OLE and HT at nutritionally relevant concentrations on peripheral blood mononuclear cells (PBMCs) as regards cell viability, frequency of leukocyte subsets, and cytokine release, performing an age-focused analysis on two groups of subj…

Analysis of T and NK cell subsets in Sicilian population from young to supercentenarian: the role of age and gender

Summary Ageing dramatically affects number and function of both innate and adaptive arms of immune system, particularly T cell subsets, contributing to reduced vaccination efficacy, decreased resistance to infections and increased prevalence of cancer in older people. In the present paper, we analysed the age‐related changes in the absolute number of lymphocytes in 214 Sicilian subjects, and in the percentages of T and natural killer (NK) cells in a subcohort of donors. We compared these results with the immunophenotype of the oldest living Italian supercentenarian (aged 111 years). The results were also sorted by gender. The correlation between number/percentage of cells and age in all ind…

Case-based surveillance of measles in Sicily during 2012-2017: The changing molecular epidemiology and implications for vaccine strategies.

Following the indication of the World Health Organization, a national plan for the elimination of measles was approved in Italy and this included the improvement of the molecular surveil- lance of measles viruses and the interruption of indigenous transmission of the disease. Nevertheless, large outbreaks continue to occur in almost all regions of the country, includ- ing Sicily. Here we describe the epidemiology and molecular dynamics of measles viruses as a result of the measles surveillance activity carried out by the “Reference Laboratory for Measles and Rubella” in Sicily over a 5-year period. Biological samples of 259 suspected measles cases were tested for viral RNA detection and a t…

Potential Therapeutic Applications of MDA-9/Syntenin-NF-κB-RKIP Loop in Human Liver Carcinoma

Background Overexpression of MDA-9/Syntenin occurs in multiple human cancer cell lines and is associated with higher grade of tumor classification, invasiveness and metastasis. In some cases, its role in cancer biology depends on relationships between MDA-9/Syntenin and NF-κB. Objective This study aims to analyze the presence of a regulation loop like that between MDA-9/Syntenin - NF-κB - RKIP in human liver carcinoma. Methods Transient transfection was performed with siRNA anti-MDA-9/Syntenin. Expression of different factors was evaluated by Real time-PCR and Western blotting, while NF-κB activation by TransAM assay. Invasion capacity was analyzed by Matrigel Invasion Assay and the effects…

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…

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…

Distribution of KIR Genes and Their HLA Ligands in Different Viral Infectious Diseases: Frequency Study in Sicilian Population

Natural killer (NK) cells play a role in defence against viral infections by killing infected cells or by producing cytokines and interacting with adaptive immune cells. Killer immunoglobulin-like receptors (KIRs) regulate the activation of NK cells through their interaction with human leucocyte antigens (HLA). Ninety-six Sicilian patients positive to Human Immunodeficiency Virus-1 (HIV) and ninety-two Sicilian patients positive to SARS-CoV-2 were genotyped for KIRs and their HLA ligands. We also included fifty-six Sicilian patients with chronic hepatitis B (CHB) already recruited in our previous study. The aim of this study was to compare the distribution of KIR–HLA genes/groups of these t…

A large view of CYP21 locus among Sicilians and other Populations: identification of a novel CYP21A2 variant in Sicily.

Background. Several mutations in CYP21 locus cause 21-Hydroxylase Deficiency (21-OHD). The most common mutations are widespread among the different geographic areas and their frequencies have been also reported to differ among certain populations. Aim. To obtain a large view on the frequencies of the most common mutations in the CYP21 locus, in Sicily, in Mediterranean and in other major geographic areas in the worldwide. Subjects and Methods. 308 unrelated CYP21A2 alleles leading 21-OHD in Sicily were genetically typed and compared with other series previously reported in Sicily and in surrounding regions. An analysis of the frequencies of the different geographic areas was also carried ou…