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Test ID: MUXF3    
MUXF3 (Cross-reactive Carbohydrate Determinant), IgE, Serum

Useful For Suggests clinical disorders or settings where the test may be helpful

Evaluation for the presence of antibodies to cross-reactive carbohydrate determinates (CCD)

 

Investigation of clinically unexpected positive IgE antibody testing in a wide variety of plant and invertebrate allergens

Clinical Information Discusses physiology, pathophysiology, and general clinical aspects, as they relate to a laboratory test

Antibodies to glycoprotein carbohydrate determinants are prone to interact with a broad variety of plant and invertebrate allergens. These glycoprotein carbohydrates have therefore been termed cross-reactive carbohydrate determinants (CCD). The MUXF3 carbohydrate epitope obtained from digested pineapple bromelain glycoprotein can be used as a representative epitope marker for assessing the presence of IgE antibodies that interact with CCD. As true allergic sensitization to the pineapple bromelain glycoprotein itself is rare, assessing for the presence IgE antibodies reactive with the bromelain MUXF3 CCD glycoprotein carbohydrate epitope serves as a well-established marker for the determination of the presence of anti-CCD IgE antibodies.

 

CCD epitopes are widely distributed in plants and invertebrate animals, and antibodies against CCD, such as MUXF2, may be associated with a number of positive IgE antibody tests (cross-reactivity) to many different and unrelated plant allergens, but also to a number of potential invertebrate allergens such as bee/wasp venom, cockroaches, mites, and shellfish. Plant protein allergens that contain CCD epitopes include peanuts, grass, pollen, and latex. The presence of anti-CCD IgE antibodies can hinder assessment of the presence of IgE antibodies to these other plant and invertebrate allergens, as it is not possible to distinguish whether observed reactivity is due to the presence of antibodies specific to other proteins, or is the result of the presence of interfering anti-CCD antibodies. When very broad allergen sensitivity profiles are observed in the course allergy testing, it may be due to the presence of cross-reactive anti-CCD IgE antibodies, although the presence of IgE antibodies to profilin proteins should also be considered.

 

The degree to which antibodies to CCD may be associated with clinical allergic reaction has not been completely resolved. In general, the presence of cross-reactive antibodies to CCD, such as MUXF3, is not thought to be clinically relevant and does not give rise to symptoms consistent with allergic reaction. However, antibodies to CCD may be linked to clinically relevant allergic reactions in extremely rare cases, including in individuals with celery and tomato allergy.

Reference Values Describes reference intervals and additional information for interpretation of test results. May include intervals based on age and sex when appropriate. Intervals are Mayo-derived, unless otherwise designated. If an interpretive report is provided, the reference value field will state this.

Class

IgE kU/L

Interpretation

0

<0.10

Negative

0/1

0.10-0.34

Borderline/Equivocal

1

0.35-0.69

Equivocal

2

0.70-3.49

Positive

3

3.50-17.4

Positive

4

17.5-49.9

Strongly positive

5

50.0-99.9

Strongly positive

6

> or =100

Strongly positive

Concentrations > or =0.70 kU/L (Class 2 and above) will flag as abnormally high.

Interpretation Provides information to assist in interpretation of the test results

Antibody to bromelain MUXF3 has widely been used for assessing for potential cross-reactive carbohydrate determinate (CCD) cross-reactivity since its CCD chain is also found in many other plant proteins, including peanuts. While sensitization to CCD is generally not associated with an allergic reaction, the presence of IgE antibodies to CCD may give rise to confounding positive IgE antibody sensitization profiles for a wide variety of plant and invertebrate allergens.

Cautions Discusses conditions that may cause diagnostic confusion, including improper specimen collection and handling, inappropriate test selection, and interfering substances

Results from IgE antibody testing must be interpreted in the context of patient’s clinical evaluation and history of allergen exposures.

 

The presence of IgE antibodies to cross-reactive carbohydrate determinant (CCD) does not rule out the presence of antibodies specific to other antigens and clinically significant allergic reaction to other antigens.

 

Testing for IgE antibodies may not be useful in patients previously treated with immunotherapy to determine if residual clinical sensitivity exists, or in patients in whom the medical management does not depend upon identification of allergen specificity.

 

False-positive results for IgE antibodies may occur in patients with markedly elevated serum IgE (>2,500 kU/L) due to nonspecific binding to allergen solid phases.

Clinical Reference Recommendations for in-depth reading of a clinical nature

1. Altmann F: Coping with cross-reactive carbohydrate determinants in allergy diagnosis. Allergo J Int. 2016;25(4):98-105. doi:10.1007/s40629-016-0115-3

2. Hemmer W, Altmann F, Holzweber F, Gruber C, Wantke F, Wohrl S: ImmunoCAP cellulose displays cross-reactive carbohydrate determinant (CCD) epitopes and can cause false-positive test results in patients with high anti-CCD IgE antibody levels. J Allergy Clin Immunol. 2018 Jan;141(1):372-381.e3. doi: 10.1016/j.jaci.2017.04.028

3. Sinson E, Ocampo C, Liao C, et al: Cross-reactive carbohydrate determinant interference in cellulose-based IgE allergy tests utilizing recombinant allergen components. PLoS One. 2020 Apr 23;15(4):e0231344. doi: 10.1371/journal.pone.0231344

4. van Ree R. Clinical importance of cross-reactivity in food allergy. Curr Opin Allergy Clin Immunol. 2004;4:235-40

5. Fotish K, Altmann F, Haustein D, Vieths S: Involvement of carbohydrate epitopes in the IgE response of celery-allergic patients. Int Arch Allergy Immunol. 1999 Sep;120:30-42. doi: 10.1159/000024217

Special Instructions Library of PDFs including pertinent information and forms related to the test