The aim of this work was to assess the impact on measurements of methylation of a panel of four cancer gene promoters of purifying tumor cells from colorectal tissue samples using the epithelial cell ...adhesion molecule (EpCAM)-immunomagnetic cell enrichment approach. We observed that, on average, methylation levels were higher in enriched cell fractions than in the whole tissue, but the difference was significant only for one out of four studied genes. In addition, there were strong correlations between methylation values for individual samples of whole tissue and the corresponding enriched cell fractions. Therefore, assays on whole tissue are likely to provide reliable estimates of tumor-specific methylation of cancer genes. However, tumor cell tissue separation using immunomagnetic beads could, in some cases, give a more accurate value of gene promoter methylation than the analysis of the whole cancer tissue, although relatively expensive and time-consuming. The efficacy and feasibility of the immunomagnetic cell sorting for methylation studies are discussed.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Following publication of the original article 1, the authors reported that the names of two institutional authors - EUROFEVER and the Paediatric Rheumatology International Trials Organisation ...(PRINTO) - had been unintentionally omitted in the final online version of the manuscript. The corrected author list is shown in this Correction..
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Dendritic cells (DCs) are effective as antigen-presenting cells in the immune system and are present at two functional stages depending on their maturation state. For experimental investigation of ...this concept, CD14
+ monocytes from blood are isolated and cultured to generate in vitro the DCs needed for functional analysis. For positive selection of CD14
+ monocytes we compared two immunomagnetic bead technologies: MACS
® Separation, created by Miltenyi Biotec, and EasySep
® Selection, created by StemCell Technologies. The monocytes provided dendritic cells for their functional analysis. Lipopolysaccharide was added to cultured DCs to induce maturation. Although both systems generated DCs from the positively selected CD14
+ cells, there were certain differences between them. Morphological, phenotypic, and functional analysis showed that MACS
®-selection provided DCs that have typical features corresponding to day 6 or 7 of maturation. EasySep
®–DCs exist in a partially-mature state from day 6 onward, even without the addition of a maturation stimulus. The reason behind this partial maturation is possibly based on the dextran-coated beads that are associated with the EasySep
® product. Both methods provide pure and viable DCs, but we would recommend using the MACS
® system for obtaining DCs suitable for functional studies.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Behçet’s Disease (BD) is an inflammatory disease of unknown etiology with multisystemic involvement, being the main clinical manifestations represented by recurrent oral and genital ulcerations and ...uveitis. The disease has typically a chronic-relapsing course and may cause significant morbidity and mortality due to eye, vascular and neurological involvement. Although BD is more frequently diagnosed in adulthood, the disease onset can also be in pediatric age. Pediatric-onset BD is commonly featured by an incomplete clinical picture, and therefore the diagnosis represents a considerable clinical challenge for the physicians. The first classification criteria for pediatric BD, based on a scoring system, have been proposed few years ago. This work focuses on the main difficulties concerning both the diagnostic approach and the treatment of BD in pediatric age. The recommendation for the treatment of pediatric BD has been recently updated and allowed a considerable improvement of the therapeutic strategies. In particular, the use of anti-TNFα drugs as a second-line option for refractory BD, and as a first-line treatment in severe ocular and neurological involvement, has demonstrated to be effective in improving the outcome of BD patients. The knowledge about the molecular pathogenesis is progressively increasing, showing that BD shares common features with autoimmune and autoinflammatory disorders, and thus leading to the use of new biologic agents targeting the main mediators involved in the determination of BD. Anti-IL-17, anti-IL-23, anti-IL-1 and anti-IL-6 agents have shown promising results for the treatment of refractory BD in clinical trials and will represent an important alternative for the therapeutic approach to the disease.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
•Uncontrolled epileptic activity leads to cognitive, motor and behavior impairment.•Seizures can activate inflammatory pathways that contribute to their persistence.•Innate immunity involvement is ...evidenced in animal models and epileptic patients.•The treatment of West Syndrome is a paradigm for other epileptic encephalopathies.•Studies should target inflammatory pathways to tailor novel anti-epileptic drugs.
In recent years, there has been an increasing interest in the potential involvement of neuroinflammation in the pathogenesis of epilepsy. Specifically, the role of innate immunity (that includes cytokines and chemokines) has been extensively investigated either in animal models of epilepsy and in clinical settings. Developmental and epileptic encephalopathies (DEE) are a heterogeneous group of epileptic disorders, in which uncontrolled epileptic activity results in cognitive, motor and behavioral impairment. By definition, epilepsy in DEE is poorly controlled by common antiepileptic drugs but may respond to alternative treatments, including steroids and immunomodulatory drugs. In this review, we will focus on how cytokines and chemokines play a role in the pathogenesis of DEE and why expanding our knowledge about the role of neuroinflammation in DEE may be crucial to develop new and effective targeted therapeutic strategies to prevent seizure recurrence and developmental regression.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
46.
Dendritic cell defects in the colorectal cancer Legitimo, Annalisa; Consolini, Rita; Failli, Alessandra ...
Human vaccines & immunotherapeutics,
11/2014, Volume:
10, Issue:
11
Journal Article
Peer reviewed
Open access
Colorectal cancer (CRC) results from the accumulation of both genetic and epigenetic alterations of the genome. However, also the formation of an inflammatory milieu plays a pivotal role in tumor ...development and progression. Dendritic cells (DCs) play a relevant role in tumor by exerting differential pro-tumorigenic and anti-tumorigenic functions, depending on the local milieu. Quantitative and functional impairments of DCs have been widely observed in several types of cancer, including CRC, representing a tumor-escape mechanism employed by cancer cells to elude host immunosurveillance.
Understanding the interactions between DCs and tumors is important for comprehending the mechanisms of tumor immune surveillance and escape, and provides novel approaches to therapy of cancer. This review summarizes updated information on the role of the DCs in colon cancer development and/or progression.
We report a case of DiGeorge-like syndrome in which immunodeficiency coexisting with juvenile idiopathic arthritis, congenital heart disease, delay in emergence of language and in motor milestones, ...feeding and growing problems, enamel hypoplasia, mild skeletal anomalies, and facial dysmorphisms are associated with no abnormalities found on genetic tests.
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FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, UL, UM, UPUK
The burden of group A streptococcus (GAS) infection and its rheumatic sequelae remains dramatically high, especially in low-income countries. Recently, an increased number of Acute Rheumatic Fever ...(ARF) cases was documented in many regions of Italy. The diagnosis of rheumatic sequelae relies on clinical signs and on the evaluation of the Antistreptolysin O titre (ASO), whose variations are globally reported. To re-examine the standard reference value of ASO titre, by measuring either its upper limit of normal (ULN) in a population of healthy children (HC) or comparing these values with streptococcal antibodies registered in a cohort of patients affected by the rheumatic sequelae of GAS infection. We performed a multicenter retrospective study. We enrolled 125 HC, aged 2–17 years, and a total of 181 patients affected by ARF, acute streptococcal pharyngitis, post-streptococcal arthritis, Henoch-Schönlein purpura and erythema nodosum, divided into four groups. The levels of ASO and anti-deoxyribonuclease B (anti-DNase B) titres were analyzed and compared among the various groups. Moreover, the 80
th
percentile value was calculated and established as the ULN for ASO titre in HC group. The ULN for ASO titre in overall HC group was 515 IU/mL, resulting in higher than used in the routine investigation. The ASO titre was significantly higher in patients with rheumatic sequelae compared with HC group, with a peak in the age between 5 and 15 years.
Conclusion
: Our study established a new ULN normal value of streptococcal serology in a childhood and adolescent population of Italy, suggesting the need to extend this revaluation to the critical areas, in order to avoid underestimating ARF diagnosis. The correct interpretation of ASO and anti-DNase B values in the context of rheumatic diseases has been discussed.
What is Known:
• The global burden of disease caused by group A streptococcus is not known and remains an important cause of morbidity and mortality. Acute rheumatic fever continues to be a serious worldwide public health problem and a recent recurrence of group A streptococcus infection cases is observed.
• The streptococcal sequelae requires evidence of preceding streptococcal infection, commonly elevated streptococcal antibody titre, but the upper limit for these titres varies considerably based on age group, region, and origin.
What is New:
• This study provides population-specific values for streptococcal antibody titres in Italy.
• Interpret the results of group A streptococcal antibody tests within the clinical context.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
X-linked agammaglobulinemia (XLA) is the prototype of primary humoral immunodeficiencies. Long-term follow-up studies regarding disease-related complications and outcome are scarce.
Our aim was to ...describe the natural history of XLA.
A nationwide multicenter study based on the Italian Primary Immunodeficiency Network registry was established in 2000 in Italy. Affected patients were enrolled by documenting centers, and the patients’ laboratory, clinical, and imaging data were recorded on an annual base.
Data on the patients (N = 168) were derived from a cumulative follow-up of 1370 patient-years, with a mean follow-up of 8.35 years per patient. The mean age at diagnosis decreased after establishment of the Italian Primary Immunodeficiency Network registry (84 months before vs 23 months after). Respiratory, skin, and gastrointestinal manifestations were the most frequent clinical symptoms at diagnosis and during long-term follow-up. Regular immunoglobulin replacement treatment reduced the incidence of invasive infections. Affected patients developed chronic lung disease over time (47% after 40 years of follow-up) in the presence of chronic sinusitis (84%). Malignancies were documented in a minority of cases (3.7%). Overall survival for affected patients was significantly reduced when compared with that for the healthy male Italian population, and it further deteriorated in the presence of chronic lung disease.
This is the first detailed long-term follow-up study for patients with XLA, revealing that although immunoglobulin replacement treatment reduces the incidence of invasive infections, it does not appear to influence the development of chronic lung disease. The overall survival of affected patients is reduced. Further studies are warranted to improve patients’ clinical management and increase awareness among physicians.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Summary
22q11.2 deletion syndrome (22q11.2DS) is characterized by a heterogeneous phenotype, including alterations in phospho‐calcium metabolism and immunodeficiency. We analyzed vitamin D status and ...the immune assessment, focusing on T cell subpopulations and dendritic cells (DCs) in a cohort of 17 pediatric 22q11.2DS patients and 17 age‐matched healthy subjects. As antigen‐presenting cells, DCs are the main target of vitamin D, promoting a tolerogenic T cell response. Patients were subdivided into three groups according to the parameters of phospho‐calcium metabolism and serum levels of 25OHD: normal values, vitamin D deficiency and hypoparathyroidism. Different degrees of T cell deficiency, ranging from normal to partial T cell numbers, were observed in the cohort of patients. The group with vitamin D deficiency showed a significant reduction of naive T cells and a significant increase of central memory T cells compared to controls. In this group the number of circulating DCs was significantly reduced. DC decrease affected both myeloid and plasmacytoid DC subsets (mDCs and pDCs), with the most relevant reduction involving pDCs. A direct correlation between 25OHD levels and recent thymic emigrant (RTE) and DC number was identified. Despite the limited cohort analyzed, our results show that deficiency of the pDC subset in patients with 22q11.2DS may be included among the causative factors of the progressive increase of risk of autoimmune diseases in these patients. As most patients suffer from increased susceptibility to infections and heightened prevalence of autoimmune disorders, we suggest a potential role of vitamin D supplementation in preventing autoimmune or proinflammatory diseases in 22q11.2DS.
This study analyzes vitamin D status and the immune assessment in patients with 22q11.2 deletion syndrome (22q11.2DS), with the main focus on dendritic cells (DCs). Patients with vitamin D deficiency show a significant reduction of DCs number, with the most relevant decrease observed in plasmacytoid DCs (pDCs). As most patients suffer from increased susceptibility to infections and heightened prevalence of autoimmune disorders, we suggest that the pDC defect could be contributing to the progressive risk of autoimmune diseases in patients with 22q11.2DS. A potential role of vitamin D supplementation in preventing autoimmune or pro‐inflammatory diseases in these patients is discussed.
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BFBNIB, DOBA, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, SIK, UILJ, UKNU, UL, UM, UPUK
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