New Perspectives on Desensitization in the Current Era - An Overview.

Blood group and tissue incompatibilities remain significant barriers to achieving transplantation. Although no patient should be labeled "un-transplantable" due to blood group or tissue incompatibility, all candidates should be provided with individualized and realistic counseling regarding their anticipated wait times for deceased donor or kidney paired donation matching, with early referral to expert centers for desensitization when needed. Vital is the careful selection of patients whose health status is such that desensitizing treatment is less likely to cause serious harm and whose anti-HLA antibody status is such that treatment is likely to accomplish the goal of increasing organ offers with an acceptable final crossmatch. Exciting new developments have re-energized the interest and scope of desensitization in the times ahead.

Antigen-Specific Treatment Modalities in MS: The Past, the Present, and the Future.

Antigen-specific therapy for multiple sclerosis may lead to a more effective therapy by induction of tolerance to a wide range of myelin-derived antigens without hampering the normal surveillance and effector function of the immune system. Numerous attempts to restore tolerance toward myelin-derived antigens have been made over the past decades, both in animal models of multiple sclerosis and in clinical trials for multiple sclerosis patients. In this review, we will give an overview of the current approaches for antigen-specific therapy that are in clinical development for multiple sclerosis as well provide an insight into the challenges for future antigen-specific treatment strategies for multiple sclerosis.

Allergen Immunotherapy in children with respiratory allergic diseases.

Allergen immunotherapy (AIT) is a well-established treatment for allergic respiratory diseases. It represents a cornerstone in the clinical management of allergic children since it is the only curative option to date able to modify the natural history of Ig-E mediated allergic diseases. Through a well-defined immunologic mechanism, AIT promotes regulatory T cells and cuts down the immune response induced by allergens. According to current guidelines based on up-to-date evidence, AIT should be offered to children with moderate-severe allergic rhinitis and/or controlled asthma starting from 5 years of age, further to an adequate risk-benefit assessment which includes patient's adherence to the treatment and a proper selection of the right product. Younger age and mild disease could be considered based on an individual evaluation. Both subcutaneous (SCIT) and sublingual (SLIT) routes of administration have a good efficacy and safety profile with safer outcomes for SLIT compared to SCIT. Only standardized products with documented evidence of clinical efficacy should be used. Although AIT is used worldwide, there are still gaps and limitations, including the lack of reliable biomarkers predictive of the clinical outcome. Novel adjuvants are currently under investigations to boost the strength and efficiency of the immune response, as well as new formulations with better efficacy and better patient's adherence to the treatment. Herein, we aim to provide an overview of current key evidence with major regard to clinical practice as well as knowledge gaps and future research needs in the context of AIT in children with respiratory allergic diseases.

Allergen Immunotherapy: History and Future Developments.

Allergen immunotherapy (AIT) was introduced in clinical practice more than 100 years ago. The clinical effectiveness in allergic rhinitis (and asthma) and in hymenoptera allergy was apparent early on but it was not until the mid-1900s that randomized placebo-controlled trials proved its efficacy. In the 1980s, sublingual immunotherapy (SLIT) was accepted in official guidelines. The availability of safer routes, such as SLIT, prompted increasing investigation of AIT for food allergy. The introduction of molecular-based diagnosis introduced the possibility of better targeted prescription of AIT. Other approaches are being explored, such as immunogenic peptides, recombinant allergens, and adjuvants.

Fifty years of allergy: 1965-2015.

The last 50 years in allergy could almost be considered the first 50 years. Over this time period, we have witnessed the emergence of allergy as a subspecialty, have seen and continue to observe a tremendous change in prevalence of allergic disease and have gained insight into the mechanisms that underlie allergic predisposition and disease manifestation. We have improved the care of children with many forms of allergic disease and now sit poised to be able to alter the natural history of allergic disease with the use of specific immunotherapy. There is much left to do in the next 50 years including understanding what underlies both the predisposition to atopic disease and its natural resolution and identifying the environmental cofactors involved in the 'allergic epidemic' and therefore targets for effective primary prevention.

Aspirin desensitization in aspirin-exacerbated respiratory disease.

Although aspirin desensitization was discovered in 1922, it was not until 1979 that a therapeutic use for aspirin treatment, under the protection of desensitization, was discovered. In the last 33 years, details of aspirin treatment have been refined to the point where it is now recognized and accepted as a major therapeutic intervention in the treatment of aspirin-exacerbated respiratory disease, with therapeutic efficacy in approximately two-thirds of patients. It is only effective in patients who have aspirin-exacerbated respiratory disease and none of the other nonsteroidal anti-inflammatory drugs, despite their cross-reactive inhibition of cyclooxygenase-1, can effectively take the place of aspirin.

Allergen immunotherapy: 100 years, but it does not look like.

Allergen immunotherapy (AIT) is the only treatment able to act on the causes and not merely on the symptoms of allergy. AIT was introduced 100 years ago but remained an empirical treatment for more than 40 years, when the first controlled trial in 1954 opened the era of scientific evidence. A major advance was the introduction of venom immunotherapy to prevent anaphylaxis from insect stings in 1978. Concerning inhalant allergens, currently AIT may be administered in two forms, subcutaneous (SCIT), and sublingual immunotherapy (SLIT). A large number of trials, globally analyzed in a number of meta-analyses, gave sound evidence to the efficacy and safety of SCIT and SLIT in allergic rhinitis and asthma. Adverse systemic reactions are still a drawback for SCIT while safety and tolerability of SLIT are very good, provided recommended doses and schedules of administration are used A significant advance for SLIT development was the registration in Europe of the standardized quality tablets. New applications, such as food allergy and atopic dermatitis, as well as new routes of administration, are currently under evaluation. After 100 years of use, AIT has a central role in the management of allergy and the ongoing improvement seems able to warrant to AIT an even brighter future.

One hundred years of immunotherapy: review of the first landmark studies.

In 2011, one hundred years of allergen immunotherapy was celebrated. Several landmark studies date from the first decades of experience with this treatment and are still cited today, often without analysis of the original articles. Original articles of the oldest landmark studies on subcutaneous immunotherapy (SCIT) and sublingual immunotherapy were sought and reviewed in detail, together with some publications on their authors' historical background. Details that might be of importance to the present allergists are highlighted in this article. Study design, preparation of allergen extracts used for immunotherapy and clinical findings of the following studies are discussed. For the European school, Noon 1911 was the first report of successful application of grass pollen extract; Frankland 1954 was the first double-blind placebo-controlled randomized trial (DBPC-RCT) in SCIT. For the European school: Noon published the first report of successful application of grass pollen extract (1911); Frankland was the first double-blind placebo-controlled randomized trial (DBPC-RCT) in SCIT (1954). For the American line: Clowes published the first successful trial of ragweed SCIT (1913); Cooke used skin prick testing as diagnostic method (1915); Loveless used venom immunotherapy with purified venom (not whole body extract) (1956); in 1961/1968 Johnstone showed in a DBPC-RCT dose-effect of an allergen mix and highly significant asthma reduction after up to 14 yrs of treatment of asthmatic children; Lowell and Franklin did the first DB-RCT demonstrating ragweed pollen efficacy as part of a multi-allergen mix and 1967 ragweed pollen extract dose response. We discuss the first studies for SLIT in 1927 from Black (oral-IT versus SCIT) and 1986 from Scadding, DBPC-RCT with house dust mite extract. We conclude that an in-depth review of investigators' observations, methods, and thoughts, however, can also be enriching for investigators in the field today.

[Allergen specific immunotherapy celebrated 100 years in 2011!]. / Allergo-immunologie. 1. L'immunothérapie spécifique d'allergène a fêté ses 100 ans en 2011!

Allergen specific immunotherapy begun 100 years ago, when Leonard Noon published his works. Important progress have been made ever since and numerous studies published. The indications enlarged with the time and thus, more allergen based treatments became available. The purpose of this article is to give a quick review of specific immunotherapy history on occasion of its centenary, and summarize the most important clinical developments reached in 2011 in this field.

One hundred years of allergen immunotherapy European Academy of Allergy and Clinical Immunology celebration: review of unanswered questions.

Allergen immunotherapy was introduced by Leonard Noon 100 years ago and is the only disease-modifying treatment for allergic individuals. Improved understanding of immunology has taught us a great deal about the underlying mechanisms involved in allergen immunotherapy; however, despite these developments, a number of important questions remain unanswered. Several of these questions relate to the practice of allergen immunotherapy in the clinic, such as: Is it possible to unify units of allergen potency? Which treatment schedules are best? Is allergen immunotherapy effective in all patient groups? Is there a dose-response relationship for efficacy and safety?, and Is there evidence for long-term effects following allergen immunotherapy? Others are related to new developments, such as new indications, or developments in the production of allergens. On the centenary of Noon's discovery, European experts in the field of immunotherapy met in Geneva under the aegis of the EAACI to discuss these controversial issues. This study presents outcomes and conclusions from these discussions.

Allergen immunotherapy: a history of the first 100 years.

PURPOSE OF REVIEW: To provide a historical perspective on the development of allergen immunotherapy and to describe the progress that has been made in both the clinical application and the scientific understanding of this therapeutic technique in the 100 years since its inception. RECENT FINDINGS: Although allergen immunotherapy has been part of allergy practice for a century, it is only in relatively recent years that the cellular and molecular mechanisms which underlie its clinical efficacy have been elucidated. Most recent studies implicate the T-regulatory cell response as central to the development of a tolerogenic state in response to allergen immunotherapy, with both IL-10 and TGF-ß playing crucial roles in the development of this cell subset. The clinical application of immunotherapy continues to advance, with promising contemporary studies noting improved safety and efficacy with pretreatment using omalizumab prior to an immunotherapy program as well as the potential for innate immune system modulation with allergen conjugates which can stimulate pattern recognition receptors such as the toll-like receptors. SUMMARY: After 100 years of clinical application, allergen immunotherapy remains the only treatment modality with the potential for long-term immunologic amelioration of atopic diseases. Future treatment advances in allergen immunotherapy will likely harness the increasing power of molecular and genomic medicine to achieve greater allergen specificity, while improving overall efficacy and minimizing the potential for systemic reactions.