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Immunoglobulin therapy in the 21st century: the dark side of the moon

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Book Series: Frontiers Research Topics ISSN: 16648714 ISBN: 9782889197033 Year: Pages: 124 DOI: 10.3389/978-2-88919-703-3 Language: English
Publisher: Frontiers Media SA
Subject: Medicine (General) --- Allergy and Immunology
Added to DOAB on : 2016-08-16 10:34:25
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In the early decades since the introduction in the early '80s of immunoglobulin therapy many studies tried to identify which clinical indications might benefit from the therapy, which treatment’s schedules are effective and safe. It is universally accepted that immunoglobulin therapy is a life-saving treatment in patients with PID. The rise of new indications for further different clinical conditions resulted in a steady increase in demand for immunoglobulins. Currently the consumption of immunoglobulin for PID represents a small fraction of the market. In the recent past we have been observing:1) An increase in the demand for plasma and in the consequent need to increase the number of donors;2) Changes in methods to improve IgG recovery and to increase productivity as a response to growing clinical demand;3) Introduction of immunoglobulin treatments with higher concentration;4) Changes in the timing of administration with an increase in the rate of infusion;5) Introduction of immunoglobulin treatment administered subcutaneously mainly confined initially to patients with PID and later extended to other clinical indications which often require higher volumes of infusion. Doctors following patients with PID were initially alarmed only to a possible risk of shortage. More relevant and less discussed appear the possible consequences of:1) the risk of an improper transfer of information on treatments from a clinical indication to another. In particular, the idea of a mere replacement function in patients with PID might possibly be borrowed from the model of other clinical conditions requiring a replacement such as haemophilia. In PID, immunoglobulin treatment instead is obviously replacing a missing feature. However, other immune alterations are responsible for the large number of PID-associated diseases including inflammatory manifestations and tumors, common causes of morbidity and mortality. The immunomodulatory effects of immunoglobulin administered at replacement dosages on multiple cells and immune system functions are still largely to be checked in in vitro studies and in vivo.2) the changes in the immunoglobulin production and schedules of administration. These should have been assessed in studies of drug surveillance, necessary in order to evaluate on large numbers of what it is initially reported on patients enrolled in the pivotal clinical trials, usually in the absence of most of the main disease-associated clinical conditions affecting pharmacokinetics, efficacy and tolerability. Severe side effects are now more frequently reported. This requires surveillance studies in order to verify the tolerability. Nowadays, personalized health research presents methodologic challenges, since emphasis is placed on the individual response rather than on the population. Even within a universally accepted indication, such as in PID, the identification of prognostic markers should guide the therapeutic intervention.3) the risk of a decrease in the surveillance and monitoring of PID-associated clinical conditions. In fact, self- administration of immunoglobulins administered subcutaneously increased the independence of a number of patients. On the other hand, it led to the reduction in the number of contacts between specialized centers and patients who often require a close monitoring of disease-associated conditions. A wide debate between experts is necessary to afford the new challenge on immunoglobulin usage.

The Evolution and Development of the Antibody Repertoire

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Book Series: Frontiers Research Topics ISSN: 16648714 ISBN: 9782889195497 Year: Pages: 122 DOI: 10.3389/978-2-88919-549-7 Language: English
Publisher: Frontiers Media SA
Subject: Allergy and Immunology --- Medicine (General)
Added to DOAB on : 2016-01-19 14:05:46
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Although at first glance mechanisms used to create the variable domains of immunoglobulin appear to be designed to generate diversity at random, closer inspection reveals striking evolutionary constraints on the sequence and structure of these antigen receptors, suggesting that natural selection is operating to create a repertoire that anticipates or is biased towards recognition of specific antigenic properties. This Research Topics issue will be devoted to an examination of the evolution of antigen receptor sequence at the germline level, an evaluation of the repertoire in B cells from fish, pigs and human, an introduction into bioinformatics approaches to the evaluation and analysis of the repertoire as ascertained by high throughput sequencing, and a discussion of how study of the normal repertoire informs the construction or selection of in vitro antibodies for applied purposes.

Natural Antibodies in Health and Disease

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Book Series: Frontiers Research Topics ISSN: 16648714 ISBN: 9782889454051 Year: Pages: 180 DOI: 10.3389/978-2-88945-405-1 Language: English
Publisher: Frontiers Media SA
Subject: Medicine (General) --- Allergy and Immunology
Added to DOAB on : 2018-11-16 17:17:57
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Natural antibodies (NAbs) are found in normal individuals in the absence of exogenous antigenic stimulation. Natural antibodies rapidly recognize and protect against pathogens that have not been previously encountered. NAbs also cross-react with several self-antigens, which, besides their role as a first line of defense against pathogens, affords them the ability to perform important housekeeping functions in healthy organisms. Such housekeeping functions include the clearance of oxidized damaged structures and/or apoptotic cells, which prevents the induction of pro-inflammatory effects. In addition, NAbs play a role in preventing the expansion of specific auto-reactive clones, thereby behaving as regulatory elements in acute or chronic inflammation. To maintain the non-pathogenic balance between the dual pathogen/self-antigen cross-reactivities of NAbs, a strict regulation in NAb secretion and function is necessary to avoid autoimmune disease. Actually, some of the NAbs related auto-reactivities, such as anti-DNA and anti-MOG, have been associated with autoimmunity. Furthermore, NAbs have been shown to bind to ‘neo-self’ carbohydrate antigens on glycolipids and glycoproteins found on malignant but not normal cells, which suggests NAbs may take part in tumor immunosurveillance.Many aspects regarding NAbs have yet to be studied in more detail: the reactivity and function of NAbs in health and disease, the behavior of the NAb repertoire with increasing age, the regulation of natural antibody production and auto-reactivity, the ways to specifically activate NAbs producing cells with desired specificities, the characteristics of human NAbs, among others. This special topics eBook consists of a number of articles exploring the cells that produce NAbs as well as the characteristics, function, specificity, and/or the role of natural antibodies in health and disease.

Epigenetics of B Cells and Antibody Responses

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Book Series: Frontiers Research Topics ISSN: 16648714 ISBN: 9782889197903 Year: Pages: 121 DOI: 10.3389/978-2-88919-790-3 Language: English
Publisher: Frontiers Media SA
Subject: Allergy and Immunology --- Medicine (General)
Added to DOAB on : 2017-02-03 17:04:57
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Epigenetics is the study of changes in gene activity that are heritable but not caused by changes in the DNA sequence. By modulating gene activities, epigenetic changes regulate cell functions. They include DNA methylation, histone posttranslational modifications and gene silencing by the action of non-coding RNAs, particularly microRNAs. It is now clear that epigenetic changes regulate B cell development. By acting in concert with networks of transcription factors, they modulate the activation of B cell lineage specific gene programs and repress inappropriate gene transcription in particular B cell differentiation states. A hallmark of B cell development in the bone marrow is the assembly of the B cell receptor (BCR) for antigen through rearrangement of immunoglobulin heavy (IgH) and light (IgL) chain V(D)J genes, as mediated by RAG1/RAG2 recombinases. Ig V(D)J rearrangement critically times the progression from pro-B cell to pre-B cell and, finally, mature B cell. Such progression is modulated by epigenetic marks, such as DNA methylation and histone posttranslational modifications, that increase chromatin accessibility and target RAG/RAG2 to V, D and J DNA. It is also dependent on the expression of multiple microRNAs. Mice deficient in Ago2, which is essential for microRNA biogenesis and function, have B cell development blocked at the pro-B cell stage. In agreement with this, B cell specific ablation of microRNA by B cell-specific knockout of Dicer virtually blocks B cell differentiation at the pro-B to pre-B cell transition. After mature B cells encounter antigen, changes of the epigenetic landscape are induced by the same stimuli that drive the antibody response; such epigenetic changes underpin the maturation of the antibody response itself. They instruct those B cell differentiation processes, somatic hypermutation (SHM), class switch DNA recombination (CSR) and plasma cell differentiation, that are central to the maturation of the antibody response as well as differentiation of memory B cells. Inducible histone modifications, together with DNA methylation and microRNAs modulate the transcriptome, particularly the expression of activation-induced cytidine deaminase (AID), central to SHM and CSR, and B lymphocyte-induced maturation protein-1 (Blimp-1), which is central to plasma cell differentiation. Combinatorial histone modifications also function as histone codes in the targeting of the CSR and, possibly, the SHM machinery to the Ig locus by recruiting specific adaptors (histone code readers) that can in turn target and/or stabilize CSR/SHM factors. Epigenetic alterations in memory B cells contribute to their functionally distinction from their naive counterparts. Memory B cells inherit epigenetic information from their precursors and acquire new epigenetic marks, which make these resting B cells poised to promptly respond to antigen. The cross/feedback regulation of different epigenetic modifications/elements further increases the complexity of the B cell epigenome, which interacts with the genetic information for precise modulation of gene expression. It is increasingly evident that epigenetic dysregulation in B cells, including aberrant expression of microRNAs, can result in aberrant antibody responses to microbial pathogens, emergence of pathogenic autoantibodies or B cell neoplastic transformation. Epigenetic marks are potential targets for new therapeutics in autoimmunity and B cell malignancy.

The Interplay of Microbiome and Immune Response in Health and Diseases

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ISBN: 9783039216468 9783039216475 Year: Pages: 206 DOI: 10.3390/books978-3-03921-647-5 Language: English
Publisher: MDPI - Multidisciplinary Digital Publishing Institute
Subject: Medicine (General) --- Internal medicine
Added to DOAB on : 2019-12-09 11:49:16
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[Increasing evidence suggests that microbiota and especially the gut microbiota (the microbes inhabiting the gut including bacteria, archaea, viruses, and fungi) plays a key role in human physiology and pathology. Recent findings indicate how dysbiosis—an imbalance in the composition and organization of microbial populations—could severely impact the development of different medical conditions (from metabolic to mood disorders), providing new insights into the comprehension of diverse diseases, such as IBD, obesity, asthma, autism, stroke, diabetes, and cancer. Given that microbial cells in the gut outnumber host cells, microbiota influences human physiology both functionally and structurally. Microbial metabolites bridge various—even distant—areas of the organism by way of the immune and hormone system. For instance, it is now clear that the mutual interaction between the gastrointestinal tract and the brain (gut–brain axis), often involves gut microbiota, indicating that the crosstalk between the organism and its microbial residents represents a fundamental aspect of both the establishment and maintenance of healthy conditions. Moreover, it is crucial to recognize that beyond the intestinal tract, microbiota populates other host organs and tissues (e.g., skin and oral mucosa). We have edited this eBook with the aim of publishing manuscripts focusing on the impact of microbiota in the development of different diseases and their associated treatments.]

Keywords

microbiota --- rheumatoid arthritis --- anti-TNF-? --- methotrexate --- etanercept --- disease activity --- microbiome --- health --- precision medicine --- genomics --- bacteriocins --- bacteriophages --- antibiotics --- gastrointestinal diseases --- dysbiosis --- gut barrier --- gut microbiota --- virus --- vaginal microbiota --- HIV --- HPV --- HSV2 --- cytokines --- chemokines --- innate immunity --- adaptive immunity --- microbiota --- autoimmunity --- etiopathogenesis --- Candida albicans --- 2,3-dihydroxy-4-methoxyBenzaldehyde --- melanin --- colitis --- anaerobic bacteria --- aerobic bacteria --- gut microbiota --- gut-liver axis --- chronic liver diseases --- fecal transplantation --- probiotics --- gut microbiota --- immunological niche --- dysbiosis --- cancer --- immune system --- cutaneous immunity --- microbiome --- Staphylococcus spp., T cells --- Staphylococcus aureus --- Staphylococcus epidermis --- commensals --- atopic dermatitis --- intravenous immunoglobulin G --- colitis --- dextran sulfate sodium --- mice --- inflammation --- cytokines --- Candida albicans --- Escherichia coli --- Enterococcus faecalis --- gut microbiota --- chemo free treatment --- lymphoid malignancies --- 16S rRNA gene --- chondroitin sulfate disaccharide --- co-occurrence network --- global network --- microbial interactions --- microbiome --- modularity --- superoxide dismutase --- gut microbiota --- macrophages --- TLR mimicry --- immune epigenetics --- metabolism --- sterile inflammation --- microbiota --- microbiome --- immunotherapy --- adoptive cell transfer (ACT) --- CAR T-cell --- TCR --- TIL --- checkpoint inhibitors --- immuno-oncology --- cancer --- diet --- n/a

Probiotics and Prebiotics in Pediatrics

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ISBN: 9783038979500 9783038979517 Year: Pages: 258 DOI: 10.3390/books978-3-03897-951-7 Language: English
Publisher: MDPI - Multidisciplinary Digital Publishing Institute
Subject: Medicine (General) --- Pediatrics
Added to DOAB on : 2019-06-26 08:44:06
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The goal of this Special Issue, “Probiotics and Prebiotics in Pediatrics”, is to focus on the importance of pediatric nutrition with probiotics and prebiotics to improve gastrointestinal health in newborn, infants, and children.Specifically, the aim is to clarify if probiotics and prebiotics can influence gut microbiota composition and host-interaction favoring human health and preventing diseases.This new information will provide health care professionals with a widespread, clear and update evidence on probiotics and prebiotics and intestinal gut microbiota in pediatric care.

Keywords

acute diarrhea --- children --- Bacillus clausii --- efficacy --- randomized controlled trials --- breast feeding --- formula feeding --- human milk oligosaccharide --- 2?-fucosyllactose --- Lacto-N-neotetraose --- microbiota --- bifidobacteria --- acute gastroenteritis --- children --- Lactobacillus reuteri --- oral rehydration solution --- probiotics --- zinc --- probiotics --- allergy --- infants --- pediatrics --- human milk oligosaccharides --- human milk --- infant formula --- necrotizing enterocolitis --- preterm infant --- preterm infant --- probiotic --- human milk --- probiotic strain --- safety --- fecal microbiota --- protein hydrolyzed formulas --- cow’s milk protein --- tolerance acquisition --- non-IgE mediated allergy --- microbiome --- intestinal microbiota --- microbial programming --- nutritional programming --- allergy --- prevention --- neonatal --- preterm --- breast milk --- oligosaccharides --- diversity --- necrotizing enterocolitis --- sepsis --- growth --- constipation --- prebiotic --- intestinal transit time --- infant --- Bifidobacterium --- Lactobacillus --- probiotics --- asthma --- Childhood Asthma Control Test --- peak expiratory flow rate --- immunoglobulin E --- “Probiotics”[Mesh] --- “Pregnancy”[Mesh] --- “Infant, Newborn”[Mesh] --- Bifidobacterium breve --- probiotics --- paediatrics --- therapeutic microbiology --- celiac disease --- iron deficiency anemia --- gluten-free diet --- inulin --- prebiotics --- iron absorption --- hepcidin --- probiotics --- microbiota --- celiac disease --- gluten free diet --- probiotics --- functional gastrointestinal disorders --- functional abdominal pain disorders --- functional constipation --- infantile colic --- infant --- colic --- lactobacilli --- n/a --- fecal microbiota --- protein hydrolyzed formulas --- cow’s milk protein --- tolerance acquisition --- non-IgE mediated allergy --- n/a

Long-Term Health Effects of the 9/11 Disaster

Authors: --- ---
ISBN: 9783039218127 9783039218134 Year: Pages: 298 DOI: 10.3390/books978-3-03921-813-4 Language: English
Publisher: MDPI - Multidisciplinary Digital Publishing Institute
Subject: Philosophy
Added to DOAB on : 2019-12-09 11:49:16
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The terrorist attacks on the World Trade Center towers on September 11, 2001, also referred as 9/11, was an iconic event in US history that altered the global and political response to terrorism. The attacks, which involved two planes hitting the twin towers in Lower Manhattan, New York City, resulted in the collapse of the buildings and over 2800 deaths of occupants of the buildings, fire, police and other responders and persons on the street in the vicinity of the collapsing buildings. The destroyed towers and the surrounding buildings have since been replaced but the health effects that resulted from the release of tons of dust, gases and debris as well as the life threat trauma are ongoing, and represent a major health burden among persons directly exposed. Hundreds of scientific publications have documented the physical and mental health effects attributed to the disaster. The current state-of-the-art in understanding the ongoing interactions of physical and mental health, especially PTSD, and the unique mechanisms by which pollutants from the building collapse, have resulted in long term pulmonary dysfunction, course of previously reported conditions, potential emerging conditions (e.g., heart disease and autoimmune diseases), as well as quality of life, functioning and unmet health care needs would be in the purview of this Special Issue on the 9/11 Disaster.

Keywords

counseling --- post-disaster --- psychotherapy --- mental health treatment --- treatment utilization --- World Trade Center --- indoor allergens sensitization --- asthma quality of life --- asthma control --- asthma outcomes --- mini asthma quality of life questionnaire --- asthma morbidity --- WTC-related asthma --- immunoglobulin E --- allergen exposure --- WTC attack --- respiratory symptoms --- lower Manhattan residents --- cleaning practices --- WTC --- fibrotic sarcoid --- injury --- inflammation --- fibrosis --- World Trade Center disaster --- pulmonary fibrosis --- dust --- injury --- physical health --- mental health --- World Trade Center disaster --- Short Form-12 (SF-12) --- HQoL --- 9/11 --- 9/11 disaster --- handgrip strength --- WTC responders --- PTSD --- depression --- aging --- 9/11 impact --- retirement --- chronic disease --- PTSD --- disaster --- income loss --- PTSD symptom change --- PCL score --- longitudinal analysis --- PTSD cluster --- WTC survivors --- 9/11 disaster --- obstructive sleep apnea --- comorbid insomnia --- sleep-related quality of life --- chronic sinusitis --- sleepiness --- WTC responders --- thyroid cancer --- 9/11 disaster --- World Trade Center --- surveillance bias --- sarcoidosis --- World Trade Center (WTC) --- Scadding stage --- lung function --- severe lung disease --- extrathoracic sarcoidosis --- cardiac sarcoidosis --- unmet mental health care needs --- Asian Americans --- World Trade Center attack --- disaster --- mental health conditions --- mental health service use --- health insurance --- social support --- stressful life events --- cognitive reserve --- cognitive decline --- latent class analysis --- disaster epidemiology --- PTSD --- airway physiology --- dust --- environmental health --- forced oscillation --- respiratory function --- small airway disease --- paresthesia --- neuropathic symptoms --- Cox regression --- hazard function --- World Trade Center exposure --- metabolic syndrome --- airway hyperreactivity --- World Trade Center --- disaster mental health --- evidence-based treatment --- mental health service utilization --- quality improvement --- 9/11 --- screening --- thyroid cancer --- biomarkers --- medical imaging --- pulmonary function tests --- lung injury --- occupational exposure --- epidemiological studies --- peripheral neuropathy --- prevalence --- World Trade Center --- rescue/recovery workers --- occupational exposure --- sarcoidosis --- World Trade Center --- 9/11 --- genetics --- firefighters --- FDNY --- 9/11 disaster --- asthma --- trigger(s) --- air pollution --- irritant(s) --- health-related quality of life --- n/a

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