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How to Test for Allergen Sensitization and Autoimmune Diseases

Diagnostic tests give reliable results that support primary care physicians as well as specialists in providing optimal patient management.

Testing to support allergy and autoimmune disease diagnosis

When a patient’s symptoms and clinical presentation offers a wide range of diagnostic possibilities, such as an IgE-mediated allergy or an autoimmune disease, test results can be a valuable tool in helping confirm the diagnosis. Together with the case history, serological testing can help you bring clarity to an uncertain diagnosis and provide clear results that are easy to interpret and explain to patients.

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Allergy
Allergy
Autoimmune Disease
Autoimmune Disease

90% increase

Adding diagnostic testing to aid in a differential diagnosis has been shown to increase confidence in diagnosis to 90 percent.1,2

Why Testing Is Important

Diagnosis based solely on physical examination, clinical observation, and patient history may result in an inaccurate or incomplete diagnosis. But adding diagnostic testing to aid in a differential diagnosis has been shown to increase confidence in diagnosis to 90 percent.1,2

Diagnostic testing can also help to improve the patient’s quality of life and productivity, reduce costs associated with absenteeism, optimize use of medication, in addition to decreasing unscheduled healthcare visits and lower medication costs.3-5

 

Testing for Allergic Conditions

IgE antibodies appear in human serum and plasma as a result of sensitization to a specific allergen. While clinical presentation and patient history may offer numerous possible causes of symptoms, diagnostic testing can narrow those possibilities and improve confidence in a diagnosis,1,2 enabling you to provide treatment tailored to your patient’s individual needs. 

Diagnostic testing provides various benefits, including:

  • Identify all allergen sensitizations
    One in three people are sensitized to at least one allergen,6 with up to 80 percent of allergy sufferers experiencing polysensitization.7 Symptoms may have different originating allergen triggers, and therefore require tailored treatment strategies.
  • Ensure the appropriate medication
    An accurate determination of one or many allergen sensitizations will help you prescribe appropriate medication, such as antihistamines or emergency medication.
  • The ability to rule out allergy
    Negative test results may enable you to rule out IgE-mediated allergy altogether as a cause of a patient’s symptoms, better enabling you to steer their treatment path, medication, and management in the correct direction.1,2
  • Identification of relevant allergy triggers
    Identifying relevant allergens that together contribute to the symptoms is a prerequisite for giving comprehensive allergen avoidance advice and keeping the patient below the symptom threshold.
  • Follow allergic diseases over time
    Recurrent testing as a follow-up strategy can be a valuable tool to track disease development or regression, and patient management may be adjusted accordingly to achieve the best possible outcomes.

A standard blood test is convenient—and can test your patients for more than 550 whole allergens and mixes, such as weeds, trees, grasses, pollen, food, and animal dander.

Benefits of quantitative blood tests in the diagnosis of allergic diseases

Measurement of circulating IgE antibodies provides an objective assessment of sensitization to an allergen. In general, low IgE antibody levels indicate a low probability of clinical disease, whereas high antibody levels to an allergen show good correlation with clinical disease.8

A standard blood test is convenient—and can test your patients for more than 550 whole allergens and mixes, such as weeds, trees, grasses, pollen, food, and animal dander. Tests are simple to perform, and can be done irrespective of age, skin condition, antihistamine use, or pregnancy.9-12

Cross-Reactivity

The potential for cross-reactivity can make diagnosing specific allergies somewhat complicated. Cross-reactivity is a phenomenon of an IgE antibody binding, and inducing an immune response to a similar allergenic protein from another source.13

Symptoms that have manifested as a result of cross-reacting antibodies cannot always be distinguished from those caused by genuine sensitization. A patient sensitized to cross-reactive components may still suffer from symptoms; albeit, normally mild-to-moderate symptoms; but by determining the primary sensitization, the patient can be effectively treated. The sensitization pattern to cross-reactive components can give important clues in how to continue the search.

 

Cross-reactivity Between Pollen and Foods (PFAS or Oral Allergy Syndrome, OAS)14

People with a primary birch pollen allergy may experience symptoms after eating raw apples, peaches, pitted fruits, carrot, peanut and hazelnut among others, because one of the proteins in these fruits is structurally similar to the major allergen in birch pollen.



Environmental

Allergen

Fruits

Vegetables

Nuts

Spices

Other

Foods

TREE POLLEN

(Typically birch and alder)

Apple, Apricot, Cherry, Kiwi, Lychee, Nectarine, Pear, Plum, Peach, Prune, Persimmon, Strawberry

Beans, Carrot, Celery, Green Pepper, Potato, Tomato, Parsnip, Peas

Almond, Hazelnut, Walnut

Anise, Basil, Caraway, Coriander, Cumin, Dill, Fennel Marjoram, Oregano, Paprika, Parsley, Pepper, Tarragon, Thyme

Lentils, Peanut, Soybean, Sunflower Seeds

GRASS

Date, Kiwi, Melons, Orange, Tomato, Watermelon

Peas, Potato

   

Peanut

MUGWORT

(More common in Europe and Asia)

Apple, Melons, Orange, Peach, Tomato, Watermelon

Carrot, Celery, Green Pepper, Onion, Parsnip

 

Anise, Basil, Caraway, Coriander, Dill, Fennel Marjoram, Mustard, Oregano, Paprika, Parsley, Pepper, Tarragon, Thyme

Chamomile, Sunflower Seeds

RAGWEED

(pollinates in autumn)

Banana, Melons (Cantaloupe, Honeydew), Watermelon

Cucumbers, Zucchini

     

 

Cross-reactivity between shellfish14

There is a high degree of cross-reactivity among the crustacean shellfish (shrimp, lobster, crab, crawfish). The risk of allergy to another crustacean shellfish is 75 percent. The risk may be lower for cross-reactivity between crustacean shellfish and non-crustacean shellfish (mollusks) such as clam, oyster, scallop, and mussels. Of note, there is cross-reactivity between chitins (a component of exoskeleton of shellfish and insects) in dust mites and crustacean shellfish, in the form of a cross-reactive risk protein called tropomyosin. This can result in in positive test results for shellfish without any clinical symptoms.

 

Cross-reactivity between latex and foods14

About 30 percent to 50 percent of people with IgE-mediated allergies to latex can experience symptoms with any or several fruits cross-reactive to latex, including most commonly banana, avocado, kiwi, and chestnut. Several types of proteins have been identified to be involved in the latex-fruit syndrome. Two of these are plant defense proteins. Class I chitinases containing an N-terminal hevein-like domain cross-react with hevein (Hev b 6.02), a major IgE-binding allergen for patients allergic to NRL. A beta-1,3-glucanase was identified as an important latex allergen which shows cross-reactivity with proteins of bell pepper.15

 

Cross-reactivity between peanut and tree nuts or seeds16

Peanut and tree nut allergies are often characterized by life-threatening anaphylactic reactions, and lifelong persistence. While peanut allergy is more commonly seen in patients, many subjects develop a hypersensitivity to both peanuts and tree nuts. Peanuts are legumes, and not related to tree nuts; however, co-allergies may exist with about 35 percent of peanut-allergic children developing a tree nut allergy. Studies have investigated the link between the two, due to cross reactivity however—walnut, pecan, and hazelnut comprise a group of strongly cross-reactive tree nuts. Hazelnut, cashew, Brazil nut, pistachio, and almond form another group of moderately cross-reactive tree nuts.

Which protein is the problem?

The stability or lability of the protein, and the amount of it contained within the allergen source, are two highly important contributing factors.

Stability: Protein families of components present in plants are ranked by their stability. The degree of stability is shared within a protein family. For instance, the families of storage proteins are very stable proteins. Proteins within the profilin and PR-10 families on the other hand, are more labile proteins.15

Lability: Labile proteins are easily broken down by processing, cooking or by enzymes in the saliva or gut, and will therefore primarily give rise to local reactions when ingested. Stable proteins, on the other hand, will reach the circulation in a more or less intact form and therefore potentially give rise to systemic reactions.15

Cross-reactive proteins are more widely distributed and may be shared between a very wide range of allergen sources. Understanding cross-reactions between species can help you to understand multiple sensitizations, for example, those seen in pollen food allergy syndrome (PFAS).

Protein Stability

Testing for Autoimmune Diseases

Autoantibodies can be specific markers for autoimmune (AI) diseases and are a key component in the diagnosis of diseases, which are often underestimated and difficult to determine. Autoimmune disorders affecting multiple organs can lead to highly variable signs and symptoms that can change in severity over time. Signs and symptoms, which are vague and slow to develop, may be present and can be misleading during diagnosis. When a patient’s clinical presentation offers a wide range of diagnostic possibilities, testing can be used to rule in or rule out multiple autoimmune diseases making it a valuable tool for getting the patients the treatment that they need. The right diagnostic testing can shorten the time from initial presentation to diagnosis that could mean you and your patients are spared years of visits, ineffective treatment and frustration. Correct test requests can also help reduce costs and improve diagnoses and referrals.

Benefits of blood testing in autoimmune diseases diagnosis

If you suspect that a patient has a certain autoimmune disease, diagnostic testing can help confirm the diagnosis. Using serological testing to identify autoimmune disease biomarkers can help you provide patients with a timely, accurate diagnosis, which has the potential to slow the progression of their disease and offer them the opportunity for symptom management.

Some other notable reasons to incorporate testing in your diagnostic process include:

1. Detecting autoantibodies early. Early diagnosis and intervention can slow or even halt the progression of symptoms in some autoimmune diseases. In rheumatoid arthritis (RA), for example, detecting positivity of the presence of specific autoantibodies, individually or in combination, increases the likelihood of disease.17 Serological testing is specific enough to allow the early identification of autoantibodies, leading to earlier diagnosis and the acceleration of treatment.

2. Broadening diagnostic range. Currently, immunoassays are available to detect autoantibodies related to autoimmune conditions, such as connective tissue diseases (CTD), RA, gluten-related disorders (GRDs), including celiac disease (CD), thyroid disease, liver disease, antiphospholipid syndrome (APS), and vasculitis. Dozens of fully automated assays are available, with the number of new tests increasing steadily.

3. Minimizing invasive diagnostic procedures. Utilizing testing can change the diagnostic process from one of exploration to one of precision. For example, CD has very sensitive and specific markers. Including test results in diagnostics of CD could replace the use of small-intestine biopsies, which can be expensive and unpleasant—especially for children who may also need anesthetics during the procedure. Waiting for a biopsy may also prolong the final diagnosis.

The role of sensitivity and specificity in the diagnosis of autoimmune diseases18

It is important to strike the right balance between sensitivity and specificity―whether within one assay or through a combination of assays.

The ability to make a diagnosis or screen for a condition depends both on the discriminatory value of the test and on the prevalence of the disease in the population of interest. Autoimmune diseases have, in general, low prevalence. When testing for diseases with low prevalence, it is crucial to have diagnostic tests with high clinical specificity to secure a correct diagnosis with minimal numbers of false positive results.

  • A marker with high specificity occurs in only one disease, i.e., CCP antibodies. A positive result for CCP antibodies is a specific marker for RA and allows an earlier diagnosis in many cases.
  • A marker with high sensitivity is detectable in all or most patients with a particular disease; antibodies against tissue transglutaminase are a good example of a marker with high sensitivity for CD.
  • A disease marker can be highly sensitive, but not very specific, such as antibodies to cardiolipin, which are a marker for APS but are also detectable in other diseases.
  • A disease marker can be highly specific but have low sensitivity, such as antibodies to Sm, which are found in only 10 to 30 percent of SLE patients but almost never in other diseases.

Test results with high clinical value are the basis of clinical decisions and the key for diagnostic success that clinicians need for their daily diagnostic decisions. Most importantly, the positive predictive reliability values and likelihood ratios of our EliA assays give excellent values assuring high clinical usefulness in routine practice.

Advanced techniques are used such as recombinant gene technology to develop the latest in standardized, precise, reliable and easy-to-use diagnostic tests. To ensure the highest quality of autoantibody tests, it is crucial to use very pure, conformationally correct antigens. We use human recombinant proteins and synthetic peptides whenever it increases antigenicity and thus sensitivity and specificity.

It is, of course, important to interpret results in the context of the patient history and clinical findings.

How autoimmune diseases can manifest over time

There are more than 120 types of autoimmune diseases,19 and some have similar symptoms. Inflammation is the most common trait, but presentation can vary widely from one condition to another, and even within the same disease. Because these conditions tend to affect multiple systems, their symptoms can be misleading, which slows down the process towards an accurate diagnosis.

Learn more about allergy testing
 

Learn more about autoimmune disease testing

References
  1. Duran-Tauleria E, Vignati G, Guedan MJ, et al. The utility of specific immunoglobulin E measurements in primary care. Allergy. 2004;59 (Suppl 78):35-41.
  2. Niggemann B, Nilsson M, Friedrichs F. Paediatric allergy diagnosis in primary care is improved by invitro allergen specific IgE testing. Pediatr Allergy Immunol. 2008;19:325-331
  3. Welsh N, et al. The Benefits of Specific Immunoglobulin E Testing in the Primary Care Setting. J Am Pharm Assoc. 2006;46:627.
  4. Szeinbach SL, Williams B, Muntendam P, et al. Identification of allergic disease among users of antihistamines. J Manag Care Pharm. 2004; 10 (3): 234-238.
  5. Szeinbach SL, Seoane-Vazquez EC, Beyer A, Williams PB. The impact of allergic rhinitis on work productivity. Prim Care Respir J. 2007;16(2):98-105.
  6. Pawankar R, at el. World Allergy Organization. White Book on Allergy (WAO). 2011. http://www.worldallergy.org/UserFiles/file/WAO-White-Book-on-Allergy_web.pdf. Accessed December 2017.
  7. Migueres M, et al. T Clin Trans Allergy. 2014;4:16.
  8. Yunginger JW, et al. J Allergy Clin Immunol. 2000;105(6pt1):1077-1084.
  9. Siles RI, Hsieh FH. Clev Clin J Med. 2011;78(9):585-592.
  10. Bonnelykke K, Pipper CB, Bisgaard H. J Allergy Clin Immunol. 2008;121(3):646-651.
  11. Belhocine W, et al. Pediatr Allergy Immunol. 2011;22:600-607.
  12. Bacharier LB, et al. Allergy. 2008;63(1):5-34.
  13. Popescu, FD. Cross-Reactivity between Aeroallergens and Food Allergens. World J Methodol. 2015;5(2):31-50.
  14. American Academy of Allergy, Asthma & Immunology. https://www.aaaai.org/conditions-and-treatments/library/allergy-library/outdoor-allergies-and-food-allergies-can-be-relate. Accessed January 2018.
  15. Molecular Allergology Users Guide. European Academy of Allergy and Clinical Immunology. 2016. http://www.eaaci.org/documents/Molecular_Allergology-web.pdf
  16. Lopata Al, Oheihir RE, Lehrer SB. Shellfish Allergy. Clin Exp Allergy. 2010;40:850-858
  17. Bas S, et al. Anti-cyclic citrullinated peptide antibodies, IgM and IgA rheumatoid factors in the diagnosis and prognosis of rheumatoid arthritis. Rheumatology. 2003;42:677–680
  18. McGee DL. Understanding Medical Tests and Test Results. http://www.merckmanuals.com/professional/special-subjects/clinical-decision-making/understanding-medical-tests-and-test-results. Accessed December 2017.
  19. American Autoimmune Related Diseases Association. https://www.aarda.org/news-information/statistics/#1488234345468-3bf2d325-1052. Accessed November 2017.