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Journal Cover Fire!!! The Multimedia Journal of Black Studies
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   ISSN (Online) 2156-4078
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  • Rhinoviruses and Their Receptors: Implications for Allergic Disease
    • Abstract: Human rhinoviruses (RVs) are picornaviruses that can cause a variety of illnesses including the common cold, lower respiratory tract illnesses such as bronchitis and pneumonia, and exacerbations of asthma. RVs are classified into three species, RV-A, B, and C, which include over 160 types. They utilize three major types of cellular membrane glycoproteins to gain entry into the host cell: intercellular adhesion molecule 1 (ICAM-1) (the majority of RV-A and all RV-B), low-density lipoprotein receptor (LDLR) family members (12 RV-A types), and cadherin-related family member 3 (CDHR3) (RV-C). CDHR3 is a member of cadherin superfamily of transmembrane proteins with yet unknown biological function, and there is relatively little information available about the mechanisms of RV-C interaction with CDHR3. A coding single nucleotide polymorphism (rs6967330) in CDHR3 could promote RV-C infections and illnesses in infancy, which could in turn adversely affect the developing lung to increase the risk of asthma. Further studies are needed to determine how RV infections contribute to pathogenesis of asthma and to develop the optimal treatment approach to control asthma exacerbations.
      PubDate: 2016-03-09
       
  • Diagnosis and Management of Rhinosinusitis: Highlights from the 2015
           Practice Parameter
    • Abstract: Rhinosinusitis is a commonly diagnosed disease in the USA. Rhinosinusitis is classified as acute, recurrent, or chronic (with or without nasal polyps). While acute rhinosinusitis is diagnosed by history and physical examination, chronic rhinosinusitis and recurrent acute rhinosinusitis are diagnosed based on symptoms and the presence of disease on either a sinus CT scan and/or endoscopy. Management of uncomplicated acute rhinosinusitis includes analgesics, saline irrigation, and/or intranasal steroids. Antibiotics and intranasal steroids are recommended for acute bacterial rhinosinusitis. Intranasal and oral steroids with antibiotics are recommended to treat chronic rhinosinusitis although the evidence for antibiotics is weak. Biologics such as omalizumab and mepolizumab are being investigated for the treatment of chronic rhinosinusitis with nasal polyps. Surgery may be indicated in management of refractory chronic rhinosinusitis and rarely for acute bacterial rhinosinusitis. This review discusses highlights of the updated 2014 practice parameter and up-to-date evidence from other literature sources.
      PubDate: 2016-03-07
       
  • Current and Emerging Therapies for IgE-Mediated Food Allergy
    • Abstract: Food allergies are a growing clinical problem leading to increased health care utilization and decreases in patient quality of life. Current treatment recommendations include strict dietary avoidance of the offending food as well as use of self-injectable epinephrine in case of accidental exposure with allergic reaction. Although many individuals will eventually outgrow their food allergies, a substantial number will not. Significant effort has been made to find novel treatments that protect patients from food-triggered reactions as well as to develop immune-modulating therapies that could lead to tolerance. In this review, three therapies that have shown the most promise for the treatment of food allergies are highlighted: oral immunotherapy, sublingual immunotherapy, and epicutaneous immunotherapy.
      PubDate: 2016-03-04
       
  • T Regulatory Cell Biology in Health and Disease
    • Abstract: Regulatory T (Treg) cells that express the transcription factor forkhead box protein P3 (FOXP3) play an essential role in enforcing immune tolerance to self tissues, regulating host-commensal flora interaction, and facilitating tissue repair. Their deficiency and/or dysfunction trigger unbridled autoimmunity and inflammation. A growing number of monogenic defects have been recognized that adversely impact Treg cell development, differentiation, and/or function, leading to heritable diseases of immune dysregulation and autoimmunity. In this article, we review recent insights into Treg cell biology and function, with particular attention to lessons learned from newly recognized clinical disorders of Treg cell deficiency.
      PubDate: 2016-02-29
       
  • Mucosal Lesions in an Allergy Practice
    • Abstract: The diagnosis and treatment of mucosal disease with an allergic pathogenesis are challenging. Oral allergy is often a hypersensitivity reaction with variable symptoms and physical exam findings. Clinical diagnosis requires a history of prior allergen exposure, a delay from exposure to clinical findings, and improvement following allergen removal. The past decades have seen great contributions to the field of oral allergy. The aim of this review is to provide an approach to the diagnosis and treatment of oral dermatologic disease with a focus on diseases with an investigated allergic pathogenesis.
      PubDate: 2016-02-27
       
  • The Heterogeneity of Oral Immunotherapy Clinical Trials: Implications and
           Future Directions
    • Abstract: Food allergy is a potentially life-threatening disease which affects up to 8 % of children and 2–3 % of adults. Increasing food allergy prevalence poses a major public health concern. Induction of desensitization to food allergens through oral immunotherapy (OIT) is an expanding area of study encompassing peanut, egg, milk, and other food allergens. OIT consists of administering incremental doses of food allergen to food-allergic patients, to induce a state of desensitization. Safety, tolerability, and efficacy all remain ongoing concerns. Clinical trials for oral immunotherapy have encompassed many variations, including differences in dosage sizes and frequency, duration of build-up, type of allergen used, patient characteristics, and adjuvant therapies. Consequently, studies have also shown variation in rates of adverse effects, and successful desensitization. Here, we provide an overview of the key studies and discuss the implications of this heterogeneity. While desensitization is successful in the majority of patients, only a minority appear to develop sustained unresponsiveness even after years of therapy. Much larger and longitudinal studies using more homogenous protocols are needed in order to evaluate the clinical applicability of OIT, its long-term effectiveness, and effect on quality of life. The role of adjunctive therapies, including omalizumab and probiotics, requires further evaluation.
      PubDate: 2016-02-27
       
  • Cross-Reactivity among Beta-Lactams
    • Abstract: Penicillins and cephalosporins are the major classes of beta-lactam (BL) antibiotics in use today and one of the most frequent causes of hypersensitivity reactions to drugs. Monobactams, carbapenems, oxacephems, and beta-lactamase inhibitors constitute the four minor classes of BLs. This review takes into account mainly the prospective studies which evaluated cross-reactivity among BLs in subjects with a well-demonstrated hypersensitivity to a certain class of BLs by performing allergy tests with alternative BLs and, in case of negative results, administering them. In subjects with either IgE-mediated or T-cell-mediated hypersensitivity, cross-reactivity among BLs, particularly among penicillins and among cephalosporins, as well as between penicillins and cephalosporins, seems to be mainly related to structural similarities among their side-chain determinants. Specifically, in penicillin-allergic subjects, cross-reactivity between penicillins and cephalosporins may exceed 30 % when they are administered cephalosporins with identical side chains to those of responsible penicillins. In these subjects, a few prospective studies have demonstrated a rate of cross-reactivity between penicillins and both carbapenems and aztreonam lower than 1 %. With regard to subjects with an IgE-mediated hypersensitivity to cephalosporins, in a single study, about 25 % of the 98 subjects with such hypersensitivity had positive results to penicillins, 3 % to aztreonam, 2 % to imipenem/cilastatin, and 1 % to meropenem. The cross-reactivity related to the selective recognition of the BL ring by IgE or T lymphocytes, which entails positive responses to all BLs tested, appears to be exceptional. Some studies concerning cross-reactivity among BLs have found patterns of allergy-test positivity which cannot be explained by either the common BL ring or by similar or identical side chains, thus indicating the possibility of coexisting sensitivities to different BLs because of prior exposures to them.
      PubDate: 2016-02-22
       
  • Potential Mechanisms for IgG4 Inhibition of Immediate Hypersensitivity
           Reactions
    • Abstract: IgG4 is the least abundant IgG subclass in human serum, representing less than 5 % of all IgG. Increases in IgG4 occur following chronic exposure to antigen and are generally associated with states of immune tolerance. In line with this, IgG4 is regarded as an anti-inflammatory antibody with a limited ability to elicit effective immune responses. Furthermore, IgG4 attenuates allergic responses by inhibiting the activity of IgE. The mechanism by which IgG4 inhibits IgE-mediated hypersensitivity has been investigated using a variety of model systems leading to two proposed mechanisms. First by sequestering antigen, IgG4 can function as a blocking antibody, preventing cross-linking of receptor bound IgE. Second IgG4 has been proposed to co-stimulate the inhibitory IgG receptor FcγRIIb, which can negatively regulate FcεRI signaling and in turn inhibit effector cell activation. Recent advances in our understanding of the structural features of human IgG4 have shed light on the unique functional and immunologic properties of IgG4. The aim of this review is to evaluate our current understanding of IgG4 biology and reassess the mechanisms by which IgG4 functions to inhibit IgE-mediated allergic responses.
      PubDate: 2016-02-18
       
  • Standardization and Regulation of Allergen Products in the European Union
    • Abstract: Product-specific standardization is of prime importance to ensure persistent quality, safety, and efficacy of allergen products. The regulatory framework in the EU has induced great advancements in the field in the last years although national implementation still remains heterogeneous. Scores of methods for quantification of individual allergen molecules are developed each year and also the challenging characterization of chemically modified allergen products is progressing. However, despite the unquestionable increase in knowledge and the subsequent improvements in control of quality parameters of allergen products, an important aim has not been reached yet, namely cross-product comparability. Still, comparison of allergen product potency, either based on total allergenic activity or individual allergen molecule content, is not possible due to a lack of standard reference preparations in conjunction with validated standard methods. This review aims at presenting the most recent developments in product-specific standardization as well as activities to facilitate cross-product comparability in the EU.
      PubDate: 2016-02-13
       
  • Classification of Food Allergens and Cross-Reactivity
    • Abstract: Patients with specific food allergies are commonly sensitized to related foods, for example, shrimp with other shellfish and peanut with other legumes. In some instances, this represents a true allergy to the related food, defined as cross-reactivity, while in other instances, it represents a positive skin or IgE test only, in a patient who can eat the related food without difficulty. This is defined as cross-sensitization. It is extremely important that the clinician recognize these patterns of cross-sensitization and cross-reactivity, both to counsel patients on foods that should be avoided and to make sure that foods are not unnecessarily restricted from the diet. In fact, it is very common for patients to be instructed to avoid entire food groups based just on positive tests, which leads to unnecessary dietary restrictions with effects on food choices, nutrition, and quality of life.
      PubDate: 2016-02-13
       
  • Autoimmune and Lymphoproliferative Complications of Common Variable
           Immunodeficiency
    • Abstract: Common variable immunodeficiency (CVID) is frequently complicated by the development of autoimmune and lymphoproliferative diseases. With widespread use of immunoglobulin replacement therapy, autoimmune and lymphoproliferative complications have replaced infection as the major cause of morbidity and mortality in CVID patients. Certain CVID complications, such as bronchiectasis, are likely to be the result of immunodeficiency and are associated with infection susceptibility. However, other complications may result from immune dysregulation rather than immunocompromise. CVID patients develop autoimmunity, lymphoproliferation, and granulomas in association with distinct immunological abnormalities. Mutations in transmembrane activator and CAML interactor, reduction of isotype-switched memory B cells, expansion of CD21 low B cells, heightened interferon signature expression, and retained B cell function are all associated with both autoimmunity and lymphoproliferation in CVID. Further research aimed to better understand that the pathological mechanisms of these shared forms of immune dysregulation may inspire therapies beneficial for multiple CVID complications.
      PubDate: 2016-02-08
       
  • Mast Cells and Anaphylaxis
    • Abstract: For half a century, it has been known that the mast cell is the cell responsible for the majority of anaphylactic events. Its mediators, taken as a whole, are capable of producing all of the clinical manifestations of these events. With the discovery of immunoglobulin E (IgE), it was originally felt that the vast majority of anaphylactic episodes were due to antigen coupling with two cell-bound IgE molecules. More recently it has been learned that many episodes are produced by direct activation of mast cells, not involving antigen binding to IgE, and that monomeric IgE under certain conditions can also cause degranulation. Of note—in regard to antigen independent degranulation—are recent reports that the human G-protein-coupled receptor, MRGPRX2, may be the receptor for many drugs and cationic proteins capable of producing direct mast cell degranulation and anaphylactic events.
      PubDate: 2016-02-08
       
  • Immediate and Delayed Hypersensitivity Reactions to Corticosteroids:
           Evaluation and Management
    • Abstract: Corticosteroids are anti-inflammatory medications used widely to treat allergic inflammation. Although the endocrine and gastrointestinal side effects of corticosteroids have been described, the occurrence of immediate hypersensitivity reactions and delayed contact dermatitis due to corticosteroids remains under-recognized. Hypersensitivity reactions can occur to a corticosteroid itself, or to the additives and vehicles in corticosteroid preparations. Skin testing and oral graded challenge can help confirm the suspected culprit agent in immediate hypersensitivity reactions and help identify an alternative tolerated corticosteroid. Patch testing can help identify the culprit agents in delayed hypersensitivity contact dermatitis. Cross-reactivity patterns have not been observed for immediate hypersensitivity reactions as they have been for delayed contact dermatitis. Sensitization in contact dermatitis exhibits cross-reactivity patterns based on corticosteroid structure. We review the current understanding regarding the clinical presentation, evaluation, and management of immediate and delayed hypersensitivity reactions to corticosteroids.
      PubDate: 2016-02-08
       
  • Immediate and Delayed Hypersensitivity Reactions to Proton Pump
           Inhibitors: Evaluation and Management
    • Abstract: PPIs are among the most commonly administered medications in the USA and are generally well tolerated. Immediate and delayed immune-mediated hypersensitivity reactions are rare but increasingly recognized adverse effects of proton pump inhibitors (PPIs). Immediate hypersensitivity reactions can occur due to IgE-mediated hypersensitivity to PPIs and can be evaluated by immediate hypersensitivity skin testing and oral provocation challenge testing. A desensitization protocol can be used when PPI use cannot be avoided in an allergic patient. Delayed hypersensitivity reactions to PPIs have also been reported. Occupational exposures causing cutaneous reactions to PPIs are the most commonly reported delayed hypersensitivity reaction, followed by drug-induced subacute cutaneous lupus erythematosus. This review presents a summary of the clinical presentation, diagnostic evaluation, and management of immune-mediated hypersensitivity reactions to PPIs.
      PubDate: 2016-01-25
       
  • Risk Factors and Comorbidities in Chronic Rhinosinusitis
    • Abstract: Chronic rhinosinusitis (CRS) is a heterogeneous disorder that creates a significant burden on the healthcare system. It is caused by a combination of inflammatory, environmental, and host factors; however, the precise mechanism of how each factor leads to CRS continues to be a source of debate. Previous data regarding this topic is often inconsistent or of lower quality. In this article, we review the recent literature on the risk factors and comorbidities in CRS. Large population-based studies have helped establish smoking as a significant risk factor for CRS. The focus has now shifted towards smoking and its effect on long-term outcomes after endoscopic sinus surgery (ESS). Ciliary dyskinesia, both primary and secondary, can affect both the sinonasal cavity and lower airways simultaneously by decreasing the beat frequency of cilia and inducing mucostasis. The effects of secondary dyskinesia may be reversible and there is some evidence to suggest the use of topical mucolytics in patients with CRS. Allergy and variants of sinonasal anatomy have been hypothesized to increase the risk of developing CRS by inducing chronic inflammation and obstructing the sinus ostia. Nevertheless, emerging data regarding these topics continue to produce inconclusive results. Inflammation of the upper and lower airways can occur simultaneously as seen in patients with asthma and aspirin sensitivity. The connection between these pro-inflammatory disease states has been known for many years. Newer evidence include large population-based studies and studies that correlate objective tests, such as computer tomography scans to pulmonary function tests. However, the treatment of CRS and its effects on obstructive airway disease continues to be a topic of debate. More large prospective studies are needed in order to continue refining our knowledge of the disease processes in CRS.
      PubDate: 2016-01-22
       
  • The Cloning and Expression of Human Monoclonal Antibodies: Implications
           for Allergen Immunotherapy
    • Abstract: Allergic responses are dependent on the highly specific effector functions of IgE antibodies. Conversely, antibodies that block the activity of IgE can mediate tolerance to allergen. Technologies that harness the unparalleled specificity of antibody responses have revolutionized the way that we diagnose and treat human disease. This area of research continues to advance at a rapid pace and has had a significant impact on our understanding of allergic disease. This review will present an overview of humoral responses and provide an up-to-date summary of technologies used in the generation of human monoclonal antibodies. The impact that monoclonal antibodies have on allergic disease will be discussed, with a particular focus on allergen immunotherapy, which remains the only form of treatment that can modulate the underlying immune mechanisms and induce long-term clinical tolerance.
      PubDate: 2016-01-16
       
  • Immune-Microbiota Interactions: Dysbiosis as a Global Health Issue
    • Abstract: Throughout evolution, microbial genes and metabolites have become integral to virtually all aspects of host physiology, metabolism and even behaviour. New technologies are revealing sophisticated ways in which microbial communities interface with the immune system, and how modern environmental changes may be contributing to the rapid rise of inflammatory noncommunicable diseases (NCDs) through declining biodiversity. The implications of the microbiome extend to virtually every branch of medicine, biopsychosocial and environmental sciences. Similarly, the impact of changes at the immune-microbiota interface are directly relevant to broader discussions concerning rapid urbanization, antibiotics, agricultural practices, environmental pollutants, highly processed foods/beverages and socioeconomic disparities—all implicated in the NCD pandemic. Here, we make the argument that dysbiosis (life in distress) is ongoing at a micro- and macro-scale and that as a central conduit of health and disease, the immune system and its interface with microbiota is a critical target in overcoming the health challenges of the twenty-first century.
      PubDate: 2016-01-14
       
  • T Cell Epitope Peptide Therapy for Allergic Diseases
    • Abstract: Careful selection of dominant T cell epitope peptides of major allergens that display degeneracy for binding to a wide array of MHC class II molecules allows induction of clinical and immunological tolerance to allergen in a refined treatment strategy. From the original concept of peptide-induced T cell anergy arising from in vitro studies, proof-of-concept murine models and flourishing human trials followed. Current randomized, double-blind, placebo-controlled clinical trials of mixtures of T cell-reactive short allergen peptides or long contiguous overlapping peptides are encouraging with intradermal administration into non-inflamed skin a preferred delivery. Definitive immunological mechanisms are yet to be resolved but specific anergy, Th2 cell deletion, immune deviation, and Treg induction seem implicated. Significant efficacy, particularly with short treatment courses, in a range of aeroallergen therapies (cat, house dust mite, grass pollen) with inconsequential non-systemic adverse events likely heralds a new class of therapeutic for allergy, Synthetic Peptide Immuno-Regulatory Epitopes (SPIRE).
      PubDate: 2016-01-14
       
  • Adherence to Sublingual Immunotherapy
    • Abstract: Adherence is a major issue in any medical treatment. Allergen immunotherapy (AIT) is particularly affected by a poor adherence because a flawed application prevents the immunological effects that underlie the clinical outcome of the treatment. Sublingual immunotherapy (SLIT) was introduced in the 1990s, and the early studies suggested that adherence and compliance to such a route of administration was better than the traditional subcutaneous route. However, the recent data from manufacturers revealed that only 13 % of patients treated with SLIT reach the recommended 3-year duration. Therefore, improved adherence to SLIT is an unmet need that may be achieved by various approaches. The utility of patient education and accurate monitoring during the treatment was demonstrated by specific studies, while the success of technology-based tools, including online platforms, social media, e-mail, and a short message service by phone, is currently considered to improve the adherence. This goal is of pivotal importance to fulfill the object of SLIT that is to modify the natural history of allergy, ensuring a long-lasting clinical benefit, and a consequent pharmaco-economic advantage, when patients complete at least a 3-year course of treatment.
      PubDate: 2016-01-13
       
  • Understanding Biofilms in Chronic Sinusitis
    • Abstract: Chronic sinusitis is a burdensome disease that has substantial individual and societal impact. Although great advances in medical and surgical therapies have been made, some patients continue to have recalcitrant infections. Microbial biofilms have been implicated as a cause of recalcitrant chronic sinusitis, and recent studies have tried to better understand the pathogenesis of chronic sinusitis as it relates to microbial biofilms. Here, we provide an overview of biofilms in chronic sinusitis with emphasis on pathogenesis, treatment, and future directions. In addition, recent evidence is presented, elucidating the role of bitter taste receptors as a possible key factor leading to biofilm formation.
      PubDate: 2016-01-13
       
 
 
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