Sublingual allergen immunotherapy for respiratory allergies: what is new?

Sublingual immunotherapy (SLIT) is a disease-modifying treatment for respiratory allergies that has been used for many years in Europe and has also recently been approved for use in North America. Its use is thus likely to increase. There is more evidence available regarding SLIT efficacy and its good safety profile, making it an appealing treatment option. The majority of studies have mostly focused on grass pollens; however, there are now data available regarding efficacy for other allergens. This review will summarize recent findings from SLIT clinical trials for respiratory allergies, including efficacy, safety, post-discontinuation effects and use in different age groups. Grass pollen, tree pollen, house dust mite and ragweed SLIT studies will be evaluated.     

Targeting IgE to facilitate oral immunotherapy for food allergy: a potential new role for anti-IgE therapy?

Food allergy is a major public health problem without satisfactory treatment options. Of several new treatments being studied, oral immunotherapy (OIT) appears to be the most promising. Unfortunately, OIT is associated with an unacceptably high frequency of allergic reactions. However, recent studies suggest that OIT might be made safer and faster when performed in conjunction with anti-IgE monoclonal antibody as an adjunctive treatment.     

Is it worthy to take full-course immunotherapy for allergic rhinitis? About efficacy biomarker of allergen immunotherapy

Nowadays, people pay more attention to biomarkers that can predict clinical efficacy of immunotherapy for allergic rhinitis. As the only recognized aetiological treatment, the efficacy of allergen immunotherapy (AIT) has been proved by many studies. However, treatment success depends on compliance and persistence greatly, which can be impaired by the lengthy duration of AIT and socioeconomic status of patients. Besides, ineffectiveness is another factor that accounts for non-adherence. If the clinical efficacy can be predicted in the early stage of immunotherapy, it can help patients choose appropriate treatment plans, increase patient compliance and optimize the allocation of medical resources. This paper mainly focuses on five candidate biomarkers, the sIgE/tIgE ratio before treatment, serum inhibitory activity for IgE, decreased basophil activation, upregulation of Tregs and tolerogenic DCs, reviews the time when potential biomarkers can predict or monitor the efficacy of AIT, discusses the reason why these indicators could serve as efficacy biomarkers and interactions among potential biomarkers.     

Standardization of allergen extracts for immunotherapy: where do we stand?

PURPOSE OF REVIEW: The current state of the art in allergen standardization and recent progress in the field is summarized, and future developments are discussed. RECENT FINDINGS: The main focus of recent research in allergen standardization was on sandwich enzyme-linked immunosorbent assays or competitive tests for the quantification of individual allergens in extracts. New assays for quantifying major or minor allergens have been developed for tree and weed pollens from the Mediterranean area, grass pollens, and foods such as peanut and apple. In several cases, a good correlation with allergenic activity, measured by inhibition tests, was obtained. In addition, the potential of cellular mediator release assays in allergen standardization was evaluated in one study. SUMMARY: Several new tests have been developed to make more major and minor allergens from various allergen sources accessible to allergen standardization programmes such as the CREATE project. It is expected that assays to determine the majority of all clinically relevant major allergens from aeroallergen sources will be available in the near future. Standardized and validated mediator release assays may be a complementary tool for evaluating the biological potency of reference allergens and for correlating allergen concentrations to biological potency.     

Is there a role for immunotherapy in controlling HIV infection?

Although HAART restores immune function in patients with HIV infection, restoration is incomplete. Functional restoration is seen primarily in responses to antigens that are prevalent in HIV-infected persons. Immunization is required to restore responses to antigens that are not predictably present. As an exception, HIV-specific responses are also generally not restored despite the prevalence of these antigens. This may be because HIV replication specifically targets and either destroys or renders nonfunctional HIV-reactive CD4+ T cells. Perhaps because HIV selectively targets HIV-reactive immune cells, therapeutic immunization strategies are particularly important areas of investigation in the treatment of HIV disease. Strategies designed to restore HIV-specific CD4+ T-cell function must also enhance the activity of HIV-specific cytolytic T cells, since these are the likely key mediators of defense against HIV replication. Both active immunization strategies and treatment interruption strategies may enhance HIV-specific immune responses. Treatment interruption, by increasing exposure to HIV antigens through heightened HIV replication, also runs the risk of permitting sufficient HIV replication to damage HIV-responsive CD4+ cells as well as enhancing the losses of other CD4+ cell populations that may protect against opportunistic complications of HIV disease. Thus, treatment interruption strategies require careful and sophisticated monitoring and should not be tried at home.     

Balancing susceptibility to infection and autoimmunity: a role for leptin?

The immune responses to many infections have long been known to share features with autoimmune responses. In particular, both types of response are typified by the enhanced reactivity of T helper 1 cells - with high levels of interleukin-2, interferon gamma and tumor necrosis factor alpha - and are accompanied often by organ-specific and/or systemic damage and the production of IgG. Paradoxically, the geographical distributions of incidence of infectious diseases and autoimmunity are complementary, rather than coincident. In less-developed societies, an epidemiological association between susceptibility to infection and malnutrition has been observed, whereas in affluent countries, an increased incidence of autoimmune diseases has been described. We suggest that these observations can be explained partly by taking into consideration the immune effects of the adipocyte-derived hormone leptin, which has been shown recently to act as a link between nutritional status and the immune response.     

Knee osteoarthritis: a role for bradykinin?

Osteoarthritis (OA) is a painful and degenerating progressive disease of the joints which affects millions of patients worldwide. The cause of OA is largely unknown. Among the potential therapies for the symptomatic treatment of OA, the intra-articular administration of a specific bradykinin (BK) B(2) receptor antagonist has been reported to produce a long lasting analgesic effect in patients affected by knee OA. BK is a vasodilator and inflammatory nonapeptide which is generated in OA synovium. It contributes to the initiation and maintenance of inflammation, to exciting and sensitizing sensory nerve fibres, thus producing pain, and to activating synoviocytes and chondrocytes which are the main cells involved in the homeostasis of synovial fluid and cartilage, respectively. Moreover, BK synergistically potentiates the effects produced by pro-inflammatory cytokines. Biochemical and preclinical evidence supporting the therapeutic relevance of B(2) receptor blockade in OA pathophysiology are reviewed in this publication.     

Allergenic extracts for specific immunotherapy: to mix or not to mix?

Immunotherapy for allergic diseases give rise to questions about when a decision must be taken to define the number of extracts to be used in a single treatment. This represents a long-lasting matter of debate between American and European allergists, which seems to be without real solution. Through the use of extract-based versus molecule-based diagnostic approaches we suggest a possible solution to this controversial issue. We used four model patients previously tested with allergenic extracts and later on selected on the basis of a panel of available allergenic molecules. Their reactivity patterns in term of extracts and molecules were compared and the decision for allergenic extract immunotherapy was made choosing either the 'classical' approach or the molecular approach. From our study it seems that molecules could offer the solution to the 'mixing' issue of allergenic extracts. This innovative approach seems to provide a solution for both the American and the European approach.     

Progression of HIV to AIDS: a protective role for HLA-B27?

HLA-B27 is known for its strong association with inflammatory spondyloarthropathies (SpA), a group of rheumatic diseases. Apart from playing its role in the onset of these inflammatory diseases, HLA-827 is so ubiquitous in the world that the carrying of this gene must have also have an advantage. There are some indications that a beneficial effect can be found as a less severe course of viral infections among B27-carriers. The literature on this subject was reviewed and revealed a favorable course of infection with influenza virus, herpes simplex type 2 virus, Epstein-Barr virus and, even more interesting, a protective effect of HLA-B27 in the progression of HIV infections. The course of HIV infection differs among individuals and is thought to be partly related to host-factor variability, reflecting broad genetic heterogeneity. The polymorphic human leukocyte antigens (HLA) are herein analyzed intensively with respect to this relationship. Cytotoxic T lymphocyte (CTL) responses, activated by HLA antigen presentation, are implicated in the control of HIV replication. An immunological explanation for the protective role for HLA B27 in HIV disease is that B27+ patients have a specific and strong CTL response against the p24 epitope, a conservative HIV protein that does not easily mutate. Some HLA genes seen in long-term non-progressors (LTNP) (>10 years disease free) are associated with a favorable prognosis. One of the alleles found predominantly in LTNPs is HLA-B27. More genetic factors seem to influence disease progression in HIV infections. Therefore, it would be interesting to further explore the influence of the genetic make up of these HIV-infected individuals. Knowledge of the immunogenetic profile might give clues for the individual course of the HIV infection, may influence the development of drug-resistant viruses and will possibly lead to a tailored therapeutic strategy in HIV-infected persons.