Specific diagnosis of HDM allergy

ALEX - the smart way of detecting house dust mite sensitisation.

We cannot see them.

But many people can feel them – house dust mites!

How can we best diagnose and specify house dust mite allergic patients?

ALEX - the smart way of detecting house dust mite sensitisation.

 

House dust mites surround us, settle in our cuddly pillows and furniture, and enjoy our dead skin cells. Eating means digesting means feces which are a major source of HDM allergens.

If you need to scratch your skin now... relax!

You have a quite good chance that you will never know that they surround you.

They are harmless creatures - until an allergy develops. These people are aware, that they have a problem.

 

What is known about house dust mites?

In Europe, Dermatophagoides spp. (Dermatophagoides pteronyssinus and Dermatophagoides farinae) that belong to the Arachnids are predominantly responsible for allergic symptoms, thereby group 1 (cysteine protease), group 2 (NPC2 family) and group 23 (Peritrophin-like protein domain) allergens are considered immunodominant (1). Allergens from D. pteronyssinus (Der p) and D. farinae (Der f) are highly cross-reactive.

 

Blomia tropicalis is a mite of the Glycyphagodae superfamily and considered as a house dust mite of tropical and subtropical areas. However, co-sensitisation to other house dust mites such as the Dermatophagoides is very common and cross-reactivity has been described. In- particular, tropomyosins such as Der p 10, Der f 10 and Blo t 10 exhibit sequence identities of more than 90% among different mite species. However, 64% of Blomia tropicals allergens are species-specific. Blo t 5 (group 5 allergens) and Blo t 21 (biological function unknown) have been revealed as major allergens. (2) Major Blomia allergens as well as Blo t 10 are covered in the ALEX panel.

 

How can such a tiny animal cause so many allergic symptoms?

Since house dust mites are nearly everywhere in our homes, symptoms of allergic patients can affect various parts of the body. They range from mild (e.g., allergic rhinitis and conjunctivitis) to more severe (e.g., bronchial asthma) respiratory symptoms. Allergic patients often describe house dust mite allergy as “an endless cold”. Due to a very close skin contact with house dust mites, the disease also affects the skin (e.g., exacerbation of atopic eczema). It is ubiquitous in human habitats and a significant risk factor for allergic rhinitis and allergic asthma.

House dust mites (HDM) are one of the most important allergen sources causing severe forms of both, respiratory and skin allergy. To date, house dust mite allergens influence up to 85% of asthmatic patients from highly populated areas and are a significant risk factor for acute symptoms among asthmatic children. (3, 4)

 

Why go for ALEX?

Diagnosis of house dust mite allergy includes the medical history of a patient, skin testing, the measurement of allergen- specific IgE antibodies and  provocation testing. However, the use of HDM allergen extracts is controversial, since serological tests can be contaminated with bacterial antigens causing false positive IgE test results. (5) On the other hand, natural HDM allergen extracts show large variabilities regarding major HDM allergen groups 1 and 2 (including major HDM allergens Der p 1, Der f 1, Der p 2, Der f 2). Moreover, essential HDM allergens with high clinical relevance, such as Der p 5, Der p 7, Der p 21 and Der p 23, might be underrepresented leading to false negative test results. (6)

Molecular diagnostic systems such as ALEX provide a comprehensive and precise diagnostic test on the molecular level for house dust mite sensitisation. Importantly, sensitivity of ALEX is comparable to extract-based testing and has the potential to evaluate the pattern of the patients’ IgE binding to many individual HDM allergens, such as Der p 1, Der p 2, Der p 5, Der p 7, Der p 10, Der p 11, Der p 20, Der p 21 and Der p 23.

ALEX provides a modern multiplex test to determine the individual sensitisation patterns of HDM allergic patients to select potential candidates for allergen immunotherapy.

 

Latest findings in house dust mite molecular diagnosis

González-Pérez et al. (7) confirmed the dominant role of sIgE sensitisation to Der p 2 and Der p 23 (86%) and Der p 1 (74%) among an asthmatic population in Spain with moderate-to-severe symptoms. Their results also demonstrated that more than 70% of the patients were sensitized to any of the major allergens, however an inclusion of allergens such as Der p 5, Der p 7 and Der p 21 enhanced diagnosis of mite-sensitized asthmatics up to >94%.

Another study (8) compared extract- based IgE testing versus molecular diagnostic tests such as singleplex assay ImmunoCAP® (detecting Der p 1, 2, 10 and 23), the multiplex assay ImmunoCAP® ISAC (detecting Der p 1, 2 and 10) and Allergy Explorer (ALEX®) versions 1 and 2 (detecting Der p 1, 2, 5, 7, 10, 11, 20, 21 and 23). In general, sensitivity of molecular tests (defined as a positive test result to at least one HDM molecule) was lower compared to singleplex extract-based testing. However, sensitivity increased the more HDM allergen molecules were included in the test. Therefore, sensitivity of ALEX was higher compared to all other molecular assays. In detail, determined sensitivities were as follows: ImmunoCAP® ISAC (88.8%), ImmunoCAP® (93%), ALEX® (93.5%) and ALEX (94.5%). A clear correlation according to sensitivity between molecular test systems with HDM sIgE levels was observed implicating that higher sIgE levels lead to better sensitivity of molecular testing.

Moreover, Der p 1, 2 and 23 were confirmed to be major allergens with sensitisation rates of 55.3%, 77.7% and 54%. Since mono‐sensitisation to Der p 5, 7, 11 or 21 was not detected in this population, these allergens do not increase sensitivity. Until now, it was supposed that Der p 1 and Der p 2 are sufficient to diagnose HDM allergy. However, this study demonstrated that Der p 23 is the third major HDM allergen and therefore essential to include in molecular test systems.

Importantly, ALEX performed statistically equal to extract-based diagnosis in patients with allergen-specific IgE levels higher that 1.0 kU/L with a sensitivity of 97.2%.

To conclude, house dust mite allergic patients recognize complex patterns of disease-eliciting allergen molecules where both - major and minor allergens play an important role. These patterns determine the therapeutic pathways and directly impact the quality of life of patients.

ALEX offers the most comprehensive panel of molecular house dust mite allergens

 

1.     doi: 10.1016/j.jaci.2016.08.014

2.     doi: 10.1159/000464325

3.     doi: 10.1016/j.jaci.2012.03.040

4.     doi: 10.1016/j.jaip.2015.06.019

5.     doi: 10.1111/all.13260

6.     doi: 10.1159/000337654

7.     doi: 10.1159/000510118

8.     doi: 10.1111/all.14271