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Paper Abstract

Monitoring allergen immunotherapy in allergic rhinitis using basophil activation test: “an allergic reaction in a test tube”

Rhinitis is a condition characterized by inflammation of the mucous membrane of the nose. It is a very prevalent condition that affects millions of people worldwide. It is manifested by sneezing, itching in the nose or throat, watery discharge, and nasal congestion. These symptoms can last for an hour in a day or for many days of the year [1].

Allergic rhinitis: all around the nose

The most prevalent type of rhinitis is allergic rhinitis, which is caused by an allergic reaction to airborne allergens such as pollen, dust, or animal dander. In the United States, it affects about 10 to 30% of adults and 40% of children, and the incidence of this disease is continuously rising [2]. Thus, the proper clinical management of allergic rhinitis can reduce the risk of developing complications of rhinitis. In most cases, allergic rhinitis can go undiagnosed, as the symptoms can resolve automatically after some hours or days. The common symptoms of allergic rhinitis include:

  • Sneezing

  • Itching

  • A blocked or runny nose

 

Usually, these signs and symptoms appear soon after allergen exposure. As a result of their sensitivity to seasonal allergens like grass or tree pollen, some people only have allergic rhinitis for a few months at a time. Some people have chronic allergic rhinitis, which affects them all through the year. The symptoms of allergic rhinitis are typically moderate and treatable with minimal effort. However, some symptoms can be severe and enduring, disrupting their sleep and interfering with daily life.

Presently, allergic rhinitis is being treated by combined strategies of allergen avoidance and allergen-specific immunotherapy (ASIT). ASIT in the treatment of allergies promotes the immune system to tolerate allergens for the long term without inhibitors. This antigen-specific immunomodulation is a singular and invaluable tool for understanding both the disease being treated and the treatment itself [1].

What is allergen-specific immunotherapy?

ASIT can be successfully used to treat IgE-mediated allergy diseases such as allergic rhinitis, which has the potential to produce long-term symptom reduction. ASIT can be used to desensitize patients with allergies. ASIT involves the administration of small doses of the offending allergen to develop tolerance and immunity. ASIT involves the administration of gradually increasing doses of an allergen to ‘re-train’ the immune system and lessen the reactivity to that allergen. ASIT is a very effective treatment for allergic rhinitis and can provide long-lasting relief.

 

Although ASIT is a life-changing treatment for many patients, the success of ASIT depends on the ability to monitor the patient's response to therapy. The effectiveness of this type of treatment for allergic rhinitis is assessed through the monitoring of allergen immunotherapy. In recent years, the basophil activation test (BAT) has emerged as a powerful tool for monitoring ASIT [3].

What is the basophil activation test?

A more accurate allergic readout than determining the concentration of allergen-specific IgE is BAT, which evaluates IgE crosslinking. BAT has several advantages compared to other testing methods. The advantages are:

  • It is less invasive.

  • It is more comfortable.

  • It is less expensive.

 

BAT is an in vitro assay that can be successfully used in the diagnosis of allergic rhinitis when standard clinical (skin prick testing) and serum antigen-specific IgE tests are unclear or inconsistent with the patient’s medical history. BAT also avoids exposing patients to the allergen under investigation because it is a laboratory test, making the diagnostic process safer and more comfortable for patients and their families.

 

The BAT is carried out by exposing the patient's blood basophils to the suspected allergen. Upon activation, basophils express selected surface markers. The activation of basophil can be detected through the upregulation of these markers. Several markers, such as CD123, IgE, CRTH2, CD107a, CD107b, CD13, CD164, CD69, p38 MAPK, and STAT5 can be used in flow cytometry to detect basophils and measure their level of activation. Basophil activation in the presence of a specific allergen is an indicator of allergy.

 

Although BAT is not frequently used in routine clinical practice, it has been demonstrated to be equivalent to conventional testing techniques and could eventually be used more frequently as a second-line diagnostic method [4], [5].

Rhinitis.jpg

What do the bat results mean?

In allergic patients, the typical result of BAT is a dose-response curve and it can be expressed as basophil reactivity and/or sensitivity. Basophil reactivity can be evaluated using %CD63 and basophils at a specific concentration or by utilizing CD-max (the concentration at which basophil activation is maximum). However, basophil sensitivity can also be specified as CD-sens (defined as the inverse of EC50 multiplied by 100) or EC50 (at this concentration 50% of the maximal basophil response takes place). Both basophil reactivity and sensitivity have been recently evaluated using the area under the dose-response curve [5].

Parameters that can influence the bat results

Variables that can alter the findings of the BAT are:

  • The time interval between the collection of blood and the performance of BAT.

  • Medications received by the patient at the time of the test.

  • The material used for basophil activation.

  • Antibodies are used for staining important markers and flow cytometry analyses [4].

A word on the BAT

BAT may be a useful tool for the diagnosis of allergic rhinitis and monitoring ASIT in allergic rhinitis patients. This test is a reliable predictor of ASIT success and may be useful in monitoring rhinitis patients during treatment. Both clinical practice and clinical studies investigating current and novel treatments for the allergic disease can greatly benefit from the utilization of BAT as it delivers consistent and reliable data. In the future, this test may become a valuable tool for assessing the efficacy of ASIT and guiding treatment decisions. The continued use of BAT in clinical practice and allergy research depends on standardization, ongoing quality assurance, and training of healthcare workers in the interpretation of BAT results.

References:

  1. N. G. Papadopoulos and G. V. Guibas, “Rhinitis Subtypes, Endotypes, and Definitions,” Immunology and Allergy Clinics of North America, vol. 36, no. 2, pp. 215–233, May 2016, DOI: 10.1016/j.iac.2015.12.001.

  2. F. C. L. Hoyte and H. S. Nelson, “Recent advances in allergic rhinitis,” F1000Res, vol. 7, p. F1000 Faculty Rev-1333, Aug. 2018, DOI: 10.12688/f1000research.15367.1.

  3. W. Moote, H. Kim, and A. K. Ellis, “Allergen-specific immunotherapy,” Allergy Asthma Clin Immunol, vol. 14, no. Suppl 2, p. 53, Sep. 2018, DOI: 10.1186/s13223-018-0282-5.

  4. A. F. Santos, O. Alpan, and H.-J. Hoffmann, “Basophil activation test: Mechanisms and considerations for use in clinical trials and clinical practice,” Allergy, vol. 76, no. 8, pp. 2420–2432, 2021, DOI: 10.1111/all.14747.

  5. O. Hemmings, M. Kwok, R. McKendry, and A. F. Santos, “Basophil Activation Test: Old and New Applications in Allergy,” Curr Allergy Asthma Rep, vol. 18, no. 12, p. 77, 2018, DOI: 10.1007/s11882-018-0831-5.

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