{"id":5200,"date":"2020-08-26T09:43:17","date_gmt":"2020-08-26T09:43:17","guid":{"rendered":"https:\/\/clinlabint.3wstaging.nl\/molecular-diagnostics-ushering-new-frontiers-in-allergy-immunotherapy\/"},"modified":"2021-01-08T11:36:10","modified_gmt":"2021-01-08T11:36:10","slug":"molecular-diagnostics-ushering-new-frontiers-in-allergy-immunotherapy","status":"publish","type":"post","link":"https:\/\/clinlabint.com\/molecular-diagnostics-ushering-new-frontiers-in-allergy-immunotherapy\/","title":{"rendered":"Molecular diagnostics – ushering new frontiers in allergy immunotherapy"},"content":{"rendered":"

Molecular allergy (MA) diagnostics determines the sensitivity of allergy patients at a molecular level. This is achieved by using recombinant allergenic molecules to determine allergic response, as opposed to the traditional method of testing crude extracts of potential allergenic sources.  Although MA diagnostics remains an emergent technique, it promises to revolutionize the diagnosis and treatment of allergies.<\/strong><\/p>\n

Classes of allergy <\/strong>
An allergy \u201cis an overreaction by the human immune system to certain substances in the environment that are usually harmless.\u201d Allergic diseases are categorized into four main types, based on reaction mechanism and time – from contact with an allergen until the appearance of the first symptoms. Clinical manifestations of allergy range from mild irritation through to potentially fatal anaphylactic shock.
The most common allergies are Type I , which involve an immediate reaction. Examples of Type I allergies include hay fever, allergies to animal hair, insect venom, latex, dust mites, asthma and hives. Allergic reactions to medication such as local anesthetics and antibiotics are also considered Type I, as are food allergies.
Other allergy types are both rare and take longer before symptoms appear: Type II (cytotoxic, such as blood transfusion reactions), Type III (immune complex allergies like arthritis and nephritis) and Type IV (delayed-onset allergies with cellular immune reactions such as organ transplant rejection).<\/p>\n

A growing and costly problem<\/strong>
Allergic diseases affect up to 25% of the population in industrialized countries and their incidence is rising, especially in children.  In the US, allergic diseases comprise the fifth leading chronic disease among all ages, and the third most common chronic disease in children under 18 years. Food allergies pose their own specific challenges. In the US, between 1997 and 2007, \u201cthe prevalence of reported food allergy increased 18% among children.\u201d In Europe, more than 17 million people have a food allergy, and hospital admissions for severe reactions in children have risen seven-fold over the past decade, according to the European Academy of Allergy and Clinical Immunology (EAACI).<\/p>\n

The economic costs of allergies include medical bills, lost work and missed school as well as what is often a dramatic reduction in the quality of life.  The cost of food allergies alone in the US is $25 billion a year. In Europe, research indicates that avoidable indirect costs per patient insufficiently treated for allergy are 2,405 euros per year due to absence from work and reduced working capacity. <\/p>\n

IgE antibody, a 1960s biomarker <\/strong>
The discovery of the immunoglobulin (IgE) antibody in the 1960s was a revolution in its time, as it provided a specific biomarker to identify allergies triggered by allergens. Traditional IgE antibody tests such as skin prick tests (SPT) or in vitro specific IgE (sIgE) tests depend on extracts of allergenic and non-allergenic molecules from an allergenic source. Even now, most patients are diagnosed by such methods. However, they are time consuming and imprecise, especially for patients with complex presentations such as multiple sensitization.<\/p>\n

Cross-reactivity, other challenges<\/strong>
Allergen components are classified by protein families based on function and structure and allergic reactions are caused by response to individual proteins which make up the allergen source. The extent of reaction varies from one protein to another, as well as between different subjects.
Another key problem with traditional tests involves the stability of an allergen. Allergens which are stable to heat and digestion are associated with severe clinical reactions, whereas heat and digestion labile molecules are likelier to cause milder, local reactions or even be tolerated.
For allergy patients, cross-reactive components (where proteins share similar structures) provoke unpleasant and sometimes severe symptoms. However, sensitization to a cross-reactive component does not indicate a primary cause. It is the latter which must be investigated thoroughly and identified in order to diagnose and manage an allergy. <\/p>\n

MA diagnostics: precision targeting<\/strong>
MA diagnostics is now offering answers to such quandaries. Rather than testing for reaction to sources, MA diagnostics tests directly for sensitivity to specific proteins – namely the allergen components. In other words, one of the most important clinical assets of MA diagnostics is its ability to reveal whether the sensitization is genuine in nature (primary, species-specific) or if it is due to cross-reactivity to proteins with similar protein structures. This, in turn, may help to evaluate the risk of reaction on exposure to different allergen sources.<\/p>\n

For clinicians, component testing enables identification of a genuine allergy as opposed to symptoms provoked by cross-reactivity (i.e. reactions due to similar protein structures). This allows them to obtain detailed information on sensitization patterns, more accurate interpretation of allergic symptoms, and thereby improve the management of an allergy.
As a result, MA diagnostics is the best way to achieve precision in searching for the primary allergen component. It also enables the design of an accurate and effective component-resolved sensitization profile for each allergy patient. Apart from resolving genuine versus cross-reactive sensitization, MA diagnostics can in certain cases also assess the risk of severe, systemic versus mild, local reactions.<\/p>\n

Recombinant technology and the fight against allergy<\/strong>
MA diagnostics was made possible by the growth of DNA technology in the late 1980s. By 1991, scientists were reporting that recombinant allergens proved useful for the \u201csetup of diagnostic tests that allow the discrimination of different IgE-binding patterns.\u201d 
Recombinant technology allows \u201cfull validation of identity, quantity, homogeneity, structure, aggregation, solubility, stability, IgE-binding and the biologic potency\u201d of allergens. These parameters had not been possible to assay and standardize for extract-based products. Finally, recombinant technology also permits bulk production of wild type molecules for diagnostics. <\/p>\n

Over the 1990s and 2000s, DNA sequences of most common allergens were isolated and produced as recombinant molecules. By 2013, a total of \u201cmore than 130 allergenic molecules\u201d were commercially available\u201d for in vitro testing.
Due to the rapid growth in the number of allergens identified, a systematic allergen nomenclature, approved by the World Health Organization (WHO) and International Union of Immunological Species (IUIS) has been established. The so-called Allergen Nomenclature Subcommittee is in charge of developing and maintaining the nomenclature for allergenic molecules, as well as a comprehensive database of known allergenic proteins (available at www.allergen.org).<\/p>\n

Singleplex and multiplex platforms<\/strong>
The process of diagnostic testing is relatively straightforward.  The presence of IgE antibodies against allergenic molecules is determined using two kinds of measurement platforms. The singleplex platform consists of one assay per sample and allows a clinician to select allergenic molecules deemed necessary for diagnosis – as determined by the clinical history of the patient. The multiplex approach, which consists of multiple assays per sample, allows characterization of the IgE response against a broad array of pre-selected allergens on a chip independently of the clinical history. <\/p>\n

Microarray-based testing<\/strong>
The near-term future promises a rapid influx of new data given growth in the availability of microarray-based tests. This will allow the design of stronger and larger number of studies \u201cto critically evaluate their diagnostic and prognostic power over existing test modalities.\u201d
A key advantage of microarray-based testing is that it requires only small volumes of serum samples to determine specific-IgE antibodies against multiple recombinants. The technique has also proven its credibility. In August 2010, the journal \u2018Clinical and Experimental Allergy\u2019 observed that the \u201cperformance characteristics of allergens so far tested are comparable with current diagnostic tests.\u201d <\/p>\n

The availability of recombinant allergens and the development of protein microarray-based immunoassays developed side-by-side over the 2000s and have now begun to cross-fertilize one another. In 2011, the \u2018Journal of Allergy and Clinical Immunology\u2019, the official publication of the American Academy of Allergy, Asthma & Immunology, noted that the \u201clong-anticipated wider application\u201d of recombinant allergens and protein microarray-based immunoassays to allergy diagnosis \u201chas recently begun to accelerate,\u201d with a demonstration of the potential \u201cfor greater resolution between clinical reactivity and asymptomatic sensitization.\u201d<\/p>\n

Printed microarrays: a promising new frontier<\/strong>
One area of growing interest is the use of printed microarrays as a platform for cellular assays. For example, protein microarray (PM) appears to be a powerful alternative to costly or labour-intensive diagnostics for large-scale detection of allergen-specific IgE. A recent study established a proof-of-concept to demonstrate that \u201ccoupling the diversity of protein array with the biological output of basophilic cells is a feasible proposition,\u201d and avoids \u201ccostly, cumbersome and time-consuming\u201d procedures for purification.<\/p>\n

MA diagnostics and personalized medicine<\/strong>
With special attention paid to species-specific or primary sensitization and cross-reactivity, MA diagnostics is also becoming a tool to determine the right treatment for a patient at the right time – in other words, a frontier for personalized medicine. Data from MA diagnostics paves the way to individualize treatment actions, including advice on targeted allergen exposure reduction and specific immunotherapy (SIT). Nevertheless, clinicians recommend that in vitro tests should be evaluated together with clinical history, because allergen sensitization does not necessarily imply clinical responsiveness.<\/p>\n

Allergen-specific immunotherapy (SIT) is the only antigen-specific and disease-modifying approach for the treatment of allergy. Though the symptoms of allergy can often be effectively suppressed using various drugs, it has been known since the late 1990s that \u201conly allergen immunotherapy is able to impact on the underlying immune mechanism and leads to long-lasting change in the course of allergic disease.\u201d It is based on the therapeutic administration of the disease-causing allergens to allergic patients.
In the past, several disadvantages limited the applicability of SIT, among them unwanted effects, poor efficacy and specificity as well as inconvenient application. Most of these were related to the poor quality of natural allergen extracts. 
Due to recent progress in molecular allergen characterization, \u201cnew allergy vaccines based on recombinant allergens, recombinant hypoallergenic allergen derivatives and allergen-derived T cell peptides have entered clinical testing and hold promise to reduce the side-effects and to increase the specificity as well as the efficacy of SIT.\u201d <\/p>\n

Towards refined immunotherapy<\/strong>
Today, the focus of attention is on what has become known as \u2018refined immunotherapy\u2019, based on the use of peptides derived from allergen surfaces that exhibit reduced, allergen-specific IgE as well as T cell reactivity. When fused to non-allergenic carriers, these peptides provide allergen-specific protective IgG responses with T cell help from a non-allergenic carrier molecule. Recent data shows that such peptide vaccines \u201ccan bypass allergen-specific IgE as well as T cell activation and may be administered at high doses without IgE- and T cell-mediated side-effects.\u201d
Such peptide vaccines are being evaluated in clinical trials. If successful, it may well be possible to develop safe forms of SIT as effective alternatives to drug-based allergy treatment.<\/p>\n","protected":false},"excerpt":{"rendered":"

Molecular allergy (MA) diagnostics determines the sensitivity of allergy patients at a molecular level. This is achieved by using recombinant allergenic molecules to determine allergic response, as opposed to the traditional method of testing crude extracts of potential allergenic sources.  Although MA diagnostics remains an emergent technique, it promises to revolutionize the diagnosis and treatment […]<\/p>\n","protected":false},"author":2,"featured_media":10080,"comment_status":"closed","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"_monsterinsights_skip_tracking":false,"_monsterinsights_sitenote_active":false,"_monsterinsights_sitenote_note":"","_monsterinsights_sitenote_category":0,"footnotes":""},"categories":[52],"tags":[],"_links":{"self":[{"href":"https:\/\/clinlabint.com\/wp-json\/wp\/v2\/posts\/5200"}],"collection":[{"href":"https:\/\/clinlabint.com\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/clinlabint.com\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/clinlabint.com\/wp-json\/wp\/v2\/users\/2"}],"replies":[{"embeddable":true,"href":"https:\/\/clinlabint.com\/wp-json\/wp\/v2\/comments?post=5200"}],"version-history":[{"count":0,"href":"https:\/\/clinlabint.com\/wp-json\/wp\/v2\/posts\/5200\/revisions"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/clinlabint.com\/wp-json\/wp\/v2\/media\/10080"}],"wp:attachment":[{"href":"https:\/\/clinlabint.com\/wp-json\/wp\/v2\/media?parent=5200"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/clinlabint.com\/wp-json\/wp\/v2\/categories?post=5200"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/clinlabint.com\/wp-json\/wp\/v2\/tags?post=5200"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}