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 or assay, including diagnostic tests in medicine, and can be a cause of false positives. In immunology, the definition of cross-reactivity refers specifically to the reaction of the immune system to antigens. There can be cross-reactivity between the immune system and the antigens of two different pathogens, or between one pathogen and proteins on non-pathogens, which in some cases can be the cause of allergies. In medical tests, including rapid diagnostic tests, cross-reactivity can be either confounding or helpful, depending on the instance. An example of confounding that yields a false positive error is in a latex fixation test when agglutination occurs with another antigen rather than the antigen of interest. An example of helpful cross-reactivity is in heterophile antibody tests, which detect Epstein-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 based assays such as ELISA and RIA. 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 on immunohistochemistry, 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.

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