搜索结果：Clinical reviews in allergy & immunology

Approximately every 5 yr, Clinical Reviews in Allergy and Immunology deviates from its usual practice of publishing volumes devoted to one theme to including papers that cover a range of subjects. This issue is one such exception and arose following a symposium at the International Institute for Research in Autoimmune Diseases named AESKU.KIPP Institute at their Wendelsheim facility. The AESKU.KIPP Institute was a particularly venue because it was initially established by a German diagnostic company and a Swiss benefactor, Karl- Heinz Kipp. The goal of the Institute was to develop a unique atmosphere to encourage original research in the field of autoimmunity and clinical immunology. The thought was to create an institute where young scientists from throughout the world could come for short periods of time to learn newer methodologies in both clinical immunology and also molecular biology. This theme contains several of the papers presented at the opening of the Institute and are incorporated herein because they focus on several unique aspects of clinical immunology, often referred to as the mosaic of autoimmunity.

Attempts to reproduce the features of human influenza in laboratory animals date from the early 1890s, when Richard Pfeiffer inoculated apes with bacteria recovered from influenza patients and produced a mild respiratory illness. Numerous studies employing nonhuman primates (NHPs) were performed during the 1918 pandemic and the following decade. Most used bacterial preparations to infect animals, but some sought a filterable agent for the disease. Since the viral etiology of influenza was established in the early 1930s, studies in NHPs have been supplemented by a much larger number of experiments in mice, ferrets and human volunteers. However, the emergence of a novel swine-origin H1N1 influenza virus in 1976 and the highly pathogenic H5N1 avian influenza virus in 1997 stimulated an increase in NHP research, because these agents are difficult to study in naturally infected patients and cannot be administered to human volunteers. In this paper, we review the published literature on the use of NHPs in influenza research from 1893 through the end of 2014. The first section summarizes observational studies of naturally occurring influenza-like syndromes in wild and captive primates, including serologic investigations. The second provides a chronological account of experimental infections of NHPs, beginning with Pfeiffer's study and covering all published research on seasonal and pandemic influenza viruses, including vaccine and antiviral drug testing. The third section reviews experimental infections of NHPs with avian influenza viruses that have caused disease in humans since 1997. The paper concludes with suggestions for further studies to more clearly define and optimize the role of NHPs as experimental animals for influenza research.

Clinicians are facing unexpected issues in everyday practice, and these may become counterintuitive or challenging. Illustrative examples are provided by the hypersensitivity to universally used immunosuppressants such as corticosteroids or antibiotics such as beta-lactam. Secondly, additional issues are represented by the discovery of new pathogenetic mechanisms involved in rheumatoid and psoriatic arthritis or other chronic inflammatory diseases, genomic susceptibility to enigmatic diseases such as giant cell arteritis, or the shared role of specific mediators such as semaphorins. Third, the therapeutic armamentarium has dramatically changed over the past decade following the introduction of biotechnological drugs, and new mechanisms are being proposed to reduce adverse events or increase the drug effectiveness, particularly on cardiovascular comorbidities. Finally, rare diseases continue to represent difficult cases, as for Cogan's syndrome, with limited literature available for clinical recommendations. For these reason, the present issue of Clinical Reviews in Allergy and Immunology is timely and dedicated to these and other unique topics in clinical immunology and allergy. The aim of this issue is thus to help clinicians involved in internal medicine as well as allergists and clinical immunologists while discussing new pathways that will prove important in the near future.

Uncommon or orphan diseases are less frequently addressed in mainstream medical journals and, as a consequence, their understanding and clinical recognition may rely on case series or anecdotal data with limited guidelines and management directions. The study of selected underrepresented autoimmune and allergy conditions is the subject of the present issue of Clinical Reviews in Allergy and Immunology to provide peculiar perspectives on common and rare themes. First, allergy remains a major concern for physicians worldwide despite the limited developments over the past years, particularly for antigens such as mite or Alternaria alternata, and due to the increasing incidence of drug hypersensitivity. Second, the female predominance of autoimmune diseases such as systemic sclerosis is well recognized but enigmatic, and a unifying hypothesis remains elusive. Third, the management of conditions triggered by infectious agents as in Guillain-Barre syndrome or mixed cryoglobulinemia is challenging, and clinical guidelines are needed in the setting of infections and autoimmunity. Fourth, gamma-delta T cells represent major players in innate immunity and are the subject of extensive studies in autoimmune diseases to provide new therapeutic targets for disease prevention or modulation in the near future. Ultimately, we acknowledge the major developments in the broad fields of rheumatology and immunology and expect that microbiota definition, epigenetics studies, and microRNA analysis will provide new exciting avenues toward the understanding and treatment of chronic and acute inflammation.

The innate immune response provides a first line of defense against common microorganisms and, for more complex and/or recurring situations where pathogens must be eliminated, an adaptive immune response has emerged and evolved to provide better protection against subsequent infections. However, such dichotomy has to be reevaluated because innate B cells (e.g., B1 and marginal zone B cells) and the newly described innate lymphoid cells (iLC) have been found to exhibit innate-like properties, such as antigen internalization, regulatory B cell functions, and helper T cell activities. In addition, the production and function of natural antibodies (nAbs) by innate B cells and their capacity to activate the classical complement pathway constitute additional important mechanisms at the junction of innate and adaptive immunity as well as the recent integration of platelets into the innate immune spectrum. There is no doubt that these mechanisms present an advantage in immunity and homeostasis particularly during the first years of life, but arguments are arising to consider that these precursors may have detrimental effects in a variety of autoimmune/inflammatory diseases, allergies and cancers, as well as in response to immunotherapy. Accordingly, and as presented in this special issue of Clinical Reviews in Allergy and Immunology, a better comprehension of the key molecular and cellular actors implicated at the crossroads of the innate and adaptive immune response represents a new challenge in our understanding of the immunological and immunopathological responses.

Intravenous immune gamma-globulin appears to have a role in the management of some autoimmune-mediated diseases. The exact mechanisms whereby IVIG is beneficial to patients with these diseases are not understood. The antiphospholipid-antibody syndrome is a recently recognized syndrome in which antibodies to negatively charged phospholipids are associated with a thrombotic diathesis, fetal wastage, and thrombocytopenia. The association between these antibodies and the clinical complaints is unknown. Recent evidence has suggested that a cofactor, a serum protein or glycoprotein (of approx 50 kDa) is essential for so-called antiphospholipid antibodies to bind to phospholipids. It may be that variations in this cofactor and its binding are some of the factors that determine whether high levels of antiphospholipid antibodies result in pathological consequences. Patients with antiphospholipid antibodies who have experienced previous fetal losses will continue to experience fetal wastage without some form of therapeutic intervention. The optimum therapy for these patients is yet to be determined, but recent isolated anecdotal reports suggest that IVIG may be of some benefit. IVIG appears to be less toxic to the mother than prednisone. The true benefit of IVIG, however, can be determined only by randomized, well controlled trials. Adequate numbers of patients could only be obtained by multicenter studies, and these should be designed to compare anticoagulation alone with anticoagulation and IVIG. Justifying a placebo group is difficult, as it is known that greater than 90% of pregnancies in women with aPL who have previously experienced fetal wastage fail to produce a live infant. It is only by doing such studies that the true role of IVIG in the management of pregnant patients with aPL can be determined.

Recent textbooks of neurology and internal medicine cite food, or pharmacologic agents in foods, as provokers of migraine (1,2). Nevertheless, this area remains controversial. Many authorities recognize foods containing pharmacologic agents, such as tyramine, as possible provokers of migraine. However, the importance of foods lacking these properties is less clear. During the 1980s, there was renewed interest in food-induced migraine. Studies have attempted to address the incidence of food-induced migraine and have recently begun to study potential mechanisms. This paper will review the general features of migraine, including prevalence, differential diagnosis, and known provokers, and then focus on the link between food and migraine.

The elevated cardiovascular morbidity in rheumatoid arthritis, systemic lupus erythematosus, and the antiphospholipid syndrome is well known, as well as the pulmonary involvement observed in these conditions and to a major extent in systemic sclerosis. These manifestations constitute a major challenge for clinicians involved in patient management. Moreover, several issues regarding the link between autoimmune rheumatic diseases and cardio pulmonary morbidity remain largely enigmatic. The mechanistic role of certain autoantibodies frequently observed in association with heart and lung diseases or the pathogenetic link between chronic inflammation and the pathways leading to atherosclerosis or pulmonary vascular changes are yet to be elucidated. As such, these questions as well as treatment strategies are of common interest to rheumatologists, immunologist, pulmonologists, and cardiologists and thus call for an interdisciplinary approach. This paradigm has been well established for rare conditions such as the Churg-Strauss syndrome. Nowadays, it seems that this approach should be expanded to encompass more common conditions such as coronary heart disease, pulmonary arterial hypertension or dilated cardiomyopathy. The present issue of Clinical Reviews in Allergy and Immunology addresses the new knowledge and concepts of autoimmune-related cardiopulmonary diseases. The issue derives from the 2010 International Autoimmunity Meeting held in Ljubljana, Slovenia and is thus timely and dedicated to the latest developments in this new multidisciplinary field.

The first textbook on autoimmunity was published by Ian Mackay and McFarland Burnett in 1963. It was the first attempt to summarize existing knowledge on human autoimmunity. Since that time, there have been tens of thousands of experimental papers and numerous textbooks that focus on the diagnosis and treatment of human autoimmunity. There have been at least as many, if not more, directed at similar issues in animal models. Enormous strides have been made not only in diagnosis, but also in the pathophysiology and especially in treatment. We have gone from the era of simple HLA typing to deep sequencing and, more recently, epigenetic analysis. We have gone from the era of white blood cell differentials to detailed lymphoid phenotyping. We have gone from the era of simple antinuclear antibodies to detailed and sophisticated immunodiagnosis with recombinant autoantigens and disease-specific epitopes. We have gone from the era of using only corticosteroids to selective biologic agents. Diseases that were previously considered idiopathic are now very much understood as autoimmune. We are in the era of autoinflammatory reactions and the concept of both innate versus adaptive immunity in mediating immunopathology. In this edition of Clinical Reviews in Allergy and Immunology, we focus on key and cutting-edge issues in the pathophysiology of autoimmunity. The issues are very much oriented and driven by hypothesis, i.e., a prediction of events expected to occur based on observations. It is not meant to be a complete summary of potential mechanisms of autoimmunity, but rather an attempt to accelerate discussion and better understanding. The primary goal is obviously to help our patients with autoimmune disease.

The most difficult component to understand in autoimmune disease has been the issue of causation. In contrast, there have been enormous gains in improved diagnostics as well as improved therapy. Indeed, the use of biologics have changed the profile of numerous autoimmune diseases. In this issue, we discuss two such aspects. Firstly, we place in perspective the use of anti-citrullinated protein antibodies in rheumatoid arthritis. Second, we discuss the increasing use of B cell depletion in the treatment of autoimmunity. Clinical Reviews in Allergy and Immunology is a unique venue for these themes because it covers the spectrum of allergy through autoimmunity. Indeed, we also present a special paper on the relationships of the hepatitis B virus and autoimmunity. Although the Th1 to Th2 dichotomy is well known to both murine and human immunologists, it is really in the study of specific inflammatory responses that they are correctly placed in the perspective of the continuum of immunopathology.

The incidence and clinical significance of allergy in cystic fibrosis have been discussed. There is little evidence that the high prevalence of positive allergy skin tests in CF is a clinical manifestation of a hypersensitivity lung disease complicating the primary pulmonary disorder, except in the special case of allergic bronchopulmonary aspergillosis. The lung disease of CF appears to be caused by excessive bronchial secretions and recurrent infection that are the result of abnormal ion transport across the apical membrane of the respiratory epithelial cell. There are two important questions concerning the allergic reactions: Are they clinically significant, and, why do they occur? The former question is partly resolved by the data presented, although well-controlled studies of intervention would help to resolve it further. The cause of these reactions, which occur particularly in relationship to the mold Aspergillus fumigatus, is unknown but the author is inclined to the view that they are the result of recurrent infection that induces heightened immunologic reactivity to inhaled allergens. The significance of AF may be simply that this mold has a "predilection for diseased airways" or may be more complex; for example, owing to abnormal ion composition in respiratory secretions, abnormal lectin expression by CF respiratory epithelial cells, or selective filtration by the airways based on particle size.

Health equity is achieved when all individuals can reach their full health potential. In food-induced anaphylaxis, this goal remains unmet. Disparities in prevalence, diagnosis, and care are influenced by race, income, and environmental determinants. This article reviews emerging evidence on inequities in food allergy, emphasizing the need to understand who is most affected and why, and outlining strategies to promote equitable prevention and treatment.

Asthma is a multifactorial, reversible, obstructive lung disease that manifests airway inflammation as well as airway hyperreactivity. In addition to IgE-mediated respiratory reactions, the pathophysiology of asthma can be triggered by both viral respiratory and bacterial sinopulmonary infections. Even though most asthma patients do not manifest undue susceptibility to infection, a subset of asthma patients with recurrent sinopulmonary as well as upper-respiratory infections may have an associated immune deficiency syndrome. In a subset of these patients, deficiencies of serum IgG subclasses have also been described in the presence of low-normal or normal serum IgG and also deficient serum IgA. In addition to the usual asthma therapy with beta 2 agonist and theophylline bronchodilators as well as cromolyn and steroids, many of these immunodeficiency patients will benefit from iv gamma-globulin therapy. However, we suggest that an inability to synthesize specific serum antibody to injected vaccines or immunogens be a prerequisite before initiating iv gamma-globulin therapy. The clinician should not rely on serum IgG subclass levels alone as a criterion for initiation of passive immune globulin therapy. There may be another cohort of asthma patients who could benefit from iv gamma-globulin therapy. In a small open-label pilot study severe steroid-dependent asthma patients who were not immunodeficient and did not have undue susceptibility to infection were treated with iv gamma-globulin with a very large dosage protocol of 2000 mg/kg monthly.(ABSTRACT TRUNCATED AT 250 WORDS)

A wide variety of fish are known to induce allergic reactions following ingestion or inhalation of vapors by sensitized individuals. Although the exact prevalence of fish sensitivity is not known, fish are among the most important food allergens; and as consumption of fish increases, rates of sensitization are expected to increase. Diagnosis of fish allergy is aided by clinical history, skin prick testing, and in vitro assays; however, double-blind placebo-controlled food challenges are the most reliable method to confirm fish allergy and to identify putative species. It appears from RAST inhibition and SDS-PAGE/Western blot studies that the current policy of recommending that fish-sensitive individuals avoid all species of fish should be reevaluated. The major allergen in codfish (Gad cI) is one of the most extensively studied of all allergens. It is a calcium-chelating protein, with a mol wt of 12,328 kDa and an isoelectric point of 4.75. As an allergen, Gad cI is very stable and its allergenic activity appears to be dependent on amino acid sequence. Crossreactivity among some fish species may be the result of common structures within related proteins.

Chronic pulmonary infection with P. aeruginosa in CF may result from: 1. An initial failure of clearance mechanisms (increased adherence) leading to the development of a highly compartmentalized inflammatory reaction; 2. Inhibition of clearing mechanisms for bacteria present in the bronchial lumen; and 3. A largely ineffective, and possibly damaging, hyperactivity of inflammatory cells in the lumen and bronchial wall. The special relationship between the CF host and P. aeruginos, always long-term, and frequently subtle in its complexity, needs further understanding in order to develop new strategies for the treatment of chronic lung infections with this organism.

The studies cited herein highlight the potential benefits of IVIG therapy in a group of neurological disorders that are associated with aberrant immune responses. Indeed, all of the disorders discussed, except epilepsy, are associated with autoreactivity. The trials are preliminary and short-term and, except for idiopathic CIDP, uncontrolled. Interpretation of the findings of these uncontrolled studies is complicated by the fact that the natural history of all of these disorders is to show fluctuations. IVIG appears to be a potentially useful and safe agent in the treatment of patients with MG, intractable epilepsy, MS, and CIDP. Its place in the therapeutic approach to these neurological diseases must await the completion of controlled trials. Since other therapeutic modalities have already proven to be useful in several of these disorders, it will be important to determine if IVIG is more efficacious, safer, and more cost-effective. It is also worth considering whether the combination of IVIG and any of these more traditional approaches would provide added therapeutic benefit.

AD is a disorder that affects up to 12% of the pediatric population. This disease is multifactorial and encompasses a wide array of etiologic factors. Strong evidence has existed in the literature over the past century for the role of inhalant and food allergies in the pathogenesis of AD. Much work is currently ongoing to delineate the role of individual cellular components, cytokines, and other mediators in the pathogenesis of AD. The answers to these questions, as well as a more comprehensive understanding of hereditary factors, will provide key information to our overall understanding of AD and our ability to treat patients with this disease more effectively in the future.

暂无摘要（点击查看详情）

Autoimmunity is believed to develop when genetically predisposed individuals encounter epigenetic modifications in response to environmental factors. Recent advances in the understanding of epigenetic mechanisms, their contribution to the immune function, and to the development of autoimmunity are presented in this special issue of Clinical Reviews in Allergy and Immunology. Potential new therapeutic strategies and biomarkers are also addressed.