Cross-reactivity, in a general sense, is the reactivity of an observed agent which initiates reactions outside the main reaction expected. This has implications for any kind of test orassay, includingdiagnostic tests in medicine, and can be a cause offalse positives. Inimmunology, the definition of cross-reactivity refers specifically to the reaction of theimmune system toantigens. There can be cross-reactivity between the immune system and the antigens of two differentpathogens, or between onepathogen and proteins on non-pathogens, which in some cases can be the cause ofallergies.
Inmedical tests, includingrapid diagnostic tests, cross-reactivity can be eitherconfounding or helpful, depending on the instance. An example of confounding that yields afalse positive error is in alatex fixation test whenagglutination occurs with another antigen rather than the antigen of interest. An example of helpful cross-reactivity is inheterophile antibody tests, which detectEpstein-Barr virus using antibodies with specificity for other antigens. Cross-reactivity is also a commonly evaluated parameter for the validation of immune and protein binding basedassays such asELISA andRIA. In this case it is normally quantified by comparing the assay's response to a range of similar analytes and expressed as a percentage. In practice,calibration curves are produced using fixed concentration ranges for a selection of related compounds and the midpoints (IC50) of the calibration curves are calculated and compared. The figure then provides an estimate of the response of the assay to possible interfering compounds relative to the target analyte.
Tissue cross-reactivity assay is a standard method based onimmunohistochemistry, required prior to phase I human studies for therapeutic antibodies.
In drug screening, because many urine drug screens use immunoassays there is a certain amount of cross-reactivity. Certain drugs or other chemicals can give a false positive for another category of drug.[1]
In immunology, cross-reactivity has a more narrow meaning of the reaction between anantibody and anantigen that differs from theimmunogen. It is sometimes also referred to as cross-immunity or cross-protective immunity,[2] although cross-reactivity does not necessarily confer cross-protection. In some cases, the cross-reactivity can be destructive, and immune response to one pathogen can interfere with or lower the immune response to a different pathogen.
Anadaptive immune response is specific to the antigen that stimulated it (called the immunogen). However, many naturally occurring apparent antigens are actually a mixture ofmacromolecules (for example, frompathogens,toxins,proteins, orpollen) comprising severalepitopes. Contact with a complex antigen such as avirus will stimulate multipleimmune responses to the virus' different macromolecules as well as the individual epitopes of each macromolecule. For example, thetetanus toxin is a single protein macromolecular antigen but will stimulate many immune responses due to thetertiary structure of the protein yielding many different epitopes. Thetoxin that creates the immune response will have an epitope on it that stimulates the response.Denaturing the protein may 'disarm' its function but allow the immune system to have an immune response thus creating an immunity without harming the patient.
Cross reactivity has implications forflu vaccination because of the large number of strains of flu, as antigens produced in response to one strain may confer protection to different strains.[3] Cross-reactivity need not be between closely related viruses, however; for example, there is cross-reactivity betweeninfluenza virus-specificCD8+T cells andhepatitis C virus antigens.[4]
Cross reactivity may also occur between a pathogen and a protein found on a non-pathogen (for example, food). There may even be cross reactivity between two non-pathogens;[5] for example,Hevein-like protein domains are a possible cause for allergen cross-reactivity betweenlatex andbanana.[6]
Cross-reactivity may be caused by identical carbohydrate structures on unrelated proteins from the same or different species. Suchcross-reactive carbohydrate determinants (CCDs) are an issue inallergy diagnosis, where about a fifth of all patients displaysIgE antibodies against Asn-linked oligosaccharides (N-glycans) containing core α1,3-linkedfucose.[7] As CCDs apparently do not elicit allergic symptoms, a positive in vitro test based on IgE binding to CCDs must be rated as false positive.
Although allergic reactions typically require prior sensitization to a specific allergen, clinical symptoms can sometimes occur upon first exposure to a food or substance; this is explained by IgE cross-reactivity, where prior sensitization to structurally homologous proteins from other sources leads the immune system to recognize similar proteins in the new allergen as triggers, even though the affected individual has never previously consumed or contacted it.[8]
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