Little is known about the distribution of lymphocyte phenotypes in young children and the association specific phenotypes may have with respiratory illnesses. The objective of this study was to describe lymphocyte distributions in children at approximately 2 years of age and to test for associations with the frequency of respiratory illness during the first 2 years of life. We hypothesized that an increased frequency of illness would be associated with those phenotypes that reflect previous antigen exposure and/or immune activation. Seventy-three children were followed during their first 2 years of life with daily symptom diaries and twice-monthly telephone calls to ascertain the incidence of respiratory illness. After the children reached 2 years of age, the phenotypes of circulating blood lymphocytes were measured by flow cytometry. Associations between illness and phenotypes were adjusted for education level of parents; hours per week in day care; hours per week exposed to environmental tobacco smoke, mould, or water damage in bedroom; and parental history of allergy and asthma. The resulting median lymphocyte count was 4.0 × 109 per litre (standard deviation, 1.3) with a CD4/CD8 count of 2.28, consistent with published values. Illness rates were positively associated with the percentage of CD8+ CD38+ T cells (unadjusted p = .03, adjusted p = .014), CD8+ CD45RO+ T cells (unadjusted p = .06, adjusted p = .036), and CD4+ CD45RO+ T cells (unadjusted p = .01, adjusted p = .005). Our conclusions is that there is an association between the distribution of lymphocyte phenotypes and the incidence of respiratory illness early in life. Future research is recommended to determine the directionality of this association.
Pediatric hemophagocytic syndrome (HS) is a severe and often fatal clinical disorder. This syndrome is frequently unrecognized, and thus, affected children may receive suboptimal management, leading to an increase in mortality. The purpose of this review is to provide a clinical guide to (1) the recognition of HS based on clinical, biologic, and pathologic features; (2) the identification of the primary cause of HS in a given affected child; and (3) the initiation of effective treatment in a timely manner.
This article summarizes and provides commentary regarding guidelines on the administration of immunotherapy (IT) for allergic airway disease. Recent investigations have provided important insights into the immunologic mechanism of IT and the prominent role of interleukin-10-producing regulatory T lymphocytes. The most important aspect of successful IT is the administration of an appropriate dose of an extract containing a sufficient concentration of the relevant allergen. This is largely possible now only with standardized extracts. When the major allergen content of successful IT extracts was quantified, efficacy was demonstrated across a surprisingly narrow concentration range (approximately 5-24 μg per injection), irrespective of the extract. This presumably reflects the concentration of an antigen that drives an immune response toward tolerance. It may be predicted that as major allergen content is quantified in currently nonstandardized extracts, effective IT will also be achieved by administering a dose in this range, in contrast to current practices involving fairly arbitrary dosing decisions. With the availability of nonsedating antihistamines, intranasal corticosteroids, and the leukotriene modifiers, inadequate pharmacologic response or intolerable side effects are less commonly the major indications for starting IT for allergic rhinitis (AR). However, with the recognition that a relatively short course (3-5 years) of IT can provide long-term immunomodulation and clinical benefit, a desire to avoid long-term pharmacotherapy and the associated high costs may be the primary indication for IT in AR cases. While evidence overwhelmingly supports the beneficial influences of IT in asthma cases, the positioning of IT for this disorder is not established. The observed prevention of asthma in children who have AR is intriguing, but further studies are required to assess the extent to which the prevalence and severity of chronic asthma will be reduced when these children reach adulthood. Similarly, safety issues overwhelmingly suggest that uncontrolled asthma is the greatest risk factor for mortality associated with IT and that IT therefore may be contraindicated for most patients who have inadequate pharmacologic responses or are unable to tolerate useful pharmacologic agents. Paradoxically, these are the patients for whom a response to IT may be most desirable.
For patients who require replacement therapy for primary immunodeficiency, subcutaneous infusions of immunoglobulin G (IgG) may be preferable to intravenous infusions for several reasons. However, at present, there is no preparation marketed for use by this route in North America. In this article, we describe the reasons patients have selected this route of therapy and the range of treatment regimens used. Approximately 20% of our patients have chosen the subcutaneous route, mainly because of adverse effects from intravenous (IV) infusions or difficulties with venous access. Unit dose regimens using whole bottles of currently available 16% intramuscular preparations or sucrose-containing lyophilized preparations intended for IV use but reconstituted to 15% IgG for subcutaneous administration were individually tailored to each patient. In most cases, self-infusions or home infusions were administered once or twice a week, most commonly requiring two subcutaneous sites and 2 to 3 hours per infusion. On average, patients took 0.18 mL of IgG per kilogram of body weight per site per hour. There were no systemic adverse effects. In patients for whom comparative data were available, trough serum IgG levels were higher with subcutaneous therapy than with IV therapy.
Both B-lymphoblastoid cell lines and tonsillar B lymphocytes express receptors for platelet-activating factor (PAF). In lymph node germinal centres, B lymphocytes interact with follicular dendritic cells (FDCs), which present antigen-containing immune complexes to B lymphocytes. FDCs have phenotypic features that are similar to those of stromal cells and monocytes and may therefore be a source of lipid mediators. In this study, we evaluated the effects of the PAF antagonist WEB 2170 on the activation of tonsillar B lymphocytes by FDCs. FDCs were isolated from tonsils by Bovine Serum Albumin (BSA) gradient centrifugation. After being cultured for 6 to 10 days, they were incubated with freshly isolated B cells in the presence or absence of the specific PAF receptor antagonist WEB 2170. B-lymphocyte proliferation was assessed by [3H]-thymidine incorporation, and immunoglobulin (Ig) G and IgM secretion was assessed by enzyme-linked immunosorbent assay (ELISA). WEB 2170 (10-6 to 10-8 M) inhibited [3H]-thymidine incorporation by up to 35% ± 3%. Moreover, the secretion of IgG and IgM was inhibited by up to 50% by WEB 2170 concentrations ranging from 10-6 to 10-8 M. There was no evidence of toxicity by trypan blue staining, and the addition of WEB 2170 to B cells in the absence of FDCs did not inhibit the spontaneous production of IgG or IgM. The effect of the PAF antagonist is primarily on B lymphocytes, as reverse transcription polymerase chain reaction detected little PAF receptor messenger ribonucleic acid (mRNA) from FDCs. These data suggest that endogenous production of PAF may be important in the interaction of B lymphocytes with FDCs.
Hypersensitivity to bloodworms (chironomid larvae) leading to asthma and other related allergic disorders is becoming common in individuals who keep or work with fish due to the increased use of bloodworms as fish food or bait.
Asthma is a very common disorder that still causes significant morbidity and mortality. A high percentage of individuals with asthma also experience exercise-induced bronchoconstriction (EIB). This article reviews the current literature and updates the reader on the safety, efficacy, and clinical applications of leukotriene modifiers in the treatment of EIB.
More and more studies are demonstrating interactions between the nervous system and the immune system. However, the functional relevance of this interaction still remains to be elucidated. Such associations have been found in the intestine between nerves and mast cells as well as between eosinophils and plasma cells. Similar morphologic associations have been demonstrated in the liver, mesentery, urinary bladder, and skin. Unmyelinated axons especially were found to associate with mast cells as well as Langerhans' cells in primate as well as murine skin. Although there are several pathways by which immune cells interact with the nervous system, the focus in this review will be on the interaction between mast cells and nerves.
Over the last few years, the evidence of links between rhinitis and asthma has been strengthened. This has led to the introduction of the concept of united airway disease. Rhinitis and asthma appear to be interrelated at the epidemiologic level and at the pathophysiologic level. This article reviews current epidemiologic and pathophysiologic evidence of the relationship between rhinitis and asthma and discusses the effect of treatment of one site on the other site.
The surgical management of chronic rhinosinusitis has evolved considerably in the last decade. We currently have a more refined understanding of the various disease entities that make up the generic diagnosis of chronic rhinosinusitis. This has led to the development of more sophisticated medical and surgical therapy for the different entities. Failure of maximal medical therapy leads to the consideration of surgical intervention with the general intent of improving the patient's quality of life. Recent technical innovations such as mucosa-preserving instrumentation and image guidance systems for intraoperative localization have given surgeons increased confidence and enabled more complete and effective surgical management of chronic rhinosinusitis, particularly in revision surgeries or in the presence of distorted landmarks. Improved packing materials and refinement of postoperative care are active areas of investigation and innovation that, it is hoped, will also translate into improved patient care.
Current guidelines for the diagnosis and treatment of osteoporosis do not address the risks to bone density and the likelihood of fracture that may be associated with inhaled corticosteroid treatment for asthma. This review outlines an approach to the use of bone densitometry in clinical practice for the diagnosis, prevention, and treatment of osteoporosis in asthmatic patients receiving inhaled corticosteroid therapy.
Numerous recombinant therapies are being investigated for the treatment of asthma. This report reviews the current status of several of these novel agents. Anti-immunoglobulin (Ig)E (omalizumab, Xolair) markedly inhibits all aspects of the allergen challenge in subjects who have reduction of free serum IgE to undetectable levels. Several clinical studies in atopic asthma have demonstrated benefit by improved symptoms and lung function and a reduction in corticosteroid requirements. Early use in atopic asthmatics may be even more effective. Several approaches target interleukin (IL)-4. Soluble IL-4 receptor has been shown to effectively replace inhaled corticosteroid; further studies are under way. Recombinant anti-IL-5 and recombinant IL-12 inhibit blood and sputum eosinophils and allergen-induced eosinophilia without any effect on airway responsiveness, allergen-induced airway responses, or allergen-induced airway hyperresponsiveness. Efalizumab, a recombinant antibody that inhibits lymphocyte trafficking, is effective in psoriasis. A bronchoprovocation study showed a reduction in allergen-induced late asthmatic response and allergen-induced eosinophilia, which suggests that it should be effective in clinical asthma. These exciting novel therapies provide not only promise of new therapies for asthma but also valuable tools for investigation of asthma mechanisms.
AIM: Pathological prion protein (PrPsc) is responsible for the development of transmissible spongiform encephalopathies (TSE). While PrPc enters the organism via the oral route, less data is available to know about its uptake and the role of gastrointestinal inflammation on the expression of prion precursor PrPc, which is constitutively expressed in the gastric mucosa.
METHODS: We studied PrPc expression in the gastric mucosa of 10 Helicobacter pylori-positive patients before and after successful H pylori eradication compared to non-infected controls using RT-PCR and Western blotting. The effect of central mediators of gastric inflammation, i.e., gastrin, prostaglandin E2 (PGE2), tumor necrosis factor alpha (TNF-α) and interleukin 1 beta (IL-1β) on PrPc expression was analyzed in gastric cell lines.
RESULTS: PrPc expression was increased in H pylori-infection compared with non-infected controls and decreased to normal after successful eradication. Gastrin, PGE2, and IL-1β dose-dependently upregulated PrPc in gastric cells, while TNF-α had no effect.
CONCLUSION: H pylori infection leads to the upregulation of gastric PrPc expression. This can be linked to H pylori induced hypergastrinemia and increased mucosal PGE2 and IL-1β synthesis. H pylori creates a milieu for enhanced propagation of prions in the gastrointestinal tract.
Prions; Helicobacter pylori; Gastrin; Pro-inflammatory cytokines