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 An assay is an investigative (analytic) procedure in laboratory medicine, mining, pharmacology, environmental biology and molecular biology for qualitatively assessing or quantitatively measuring the presence, amount, or functional activity of a ...

, including

diagnostic tests A medical test is a medical procedure performed to screening (medicine), detect, medical diagnosis, diagnose, or monitoring (medicine), monitor diseases, disease processes, susceptibility, or to determine a course of treatment. Medical tests suc ...

in medicine, and can be a cause of

false positives A false positive is an error in binary classification in which a test result incorrectly indicates the presence of a condition (such as a disease when the disease is not present), while a false negative is the opposite error, where the test result ...

. In

immunology Immunology is a branch of medicineImmunology for Medical Students, Roderick Nairn, Matthew Helbert, Mosby, 2007 and biology that covers the medical study of immune systems in humans, animals, plants and sapient species. In such we can see there ...

, the definition of cross-reactivity refers specifically to the reaction of the

immune system The immune system is a network of biological processes that protects an organism from diseases. It detects and responds to a wide variety of pathogens, from viruses to parasitic worms, as well as cancer cells and objects such as wood splinte ...

antigens In immunology, an antigen (Ag) is a molecule or molecular structure or any foreign particulate matter or a pollen grain that can bind to a specific antibody or T-cell receptor. The presence of antigens in the body may trigger an immune response. ...

. There can be cross-reactivity between the immune system and the antigens of two different

pathogens In biology, a pathogen ( el, πάθος, "suffering", "passion" and , "producer of") in the oldest and broadest sense, is any organism or agent that can produce disease. A pathogen may also be referred to as an infectious agent, or simply a germ ...

, or between one

pathogen In biology, a pathogen ( el, πάθος, "suffering", "passion" and , "producer of") in the oldest and broadest sense, is any organism or agent that can produce disease. A pathogen may also be referred to as an infectious agent, or simply a germ ...

and proteins on non-pathogens, which in some cases can be the cause of

allergies Allergies, also known as allergic diseases, refer a number of conditions caused by the hypersensitivity of the immune system to typically harmless substances in the environment. These diseases include hay fever, food allergies, atopic derma ...

In medical testing

medical test A medical test is a medical procedure performed to detect, diagnose, or monitor diseases, disease processes, susceptibility, or to determine a course of treatment. Medical tests such as, physical and visual exams, diagnostic imaging, genetic te ...

s, including

rapid diagnostic test A rapid diagnostic test (RDT) is a medical diagnostic test that is quick and easy to perform. RDTs are suitable for preliminary or emergency medical screening and for use in medical facilities with limited resources. They also allow point-of-care t ...

s, cross-reactivity can be either

confounding In statistics, a confounder (also confounding variable, confounding factor, extraneous determinant or lurking variable) is a variable that influences both the dependent variable and independent variable, causing a spurious association. Con ...

or helpful, depending on the instance. An example of confounding that yields a false positive error is in a

latex fixation test A latex fixation test, also called a latex agglutination assay or test (LA assay or test), is an assay used clinically in the identification and typing of many important microorganisms. These tests use the patient's antigen-antibody immune respon ...

when

agglutination In linguistics, agglutination is a morphological process in which words are formed by stringing together morphemes, each of which corresponds to a single syntactic feature. Languages that use agglutination widely are called agglutinative lang ...

occurs with another antigen rather than the antigen of interest. An example of helpful cross-reactivity is in

heterophile antibody test The mononuclear spot test or monospot test, a form of the heterophile antibody test, is a rapid test for infectious mononucleosis due to Epstein–Barr virus (EBV). It is an improvement on the Paul–Bunnell test. The test is specific for heterop ...

s, 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

s such as

ELISA The enzyme-linked immunosorbent assay (ELISA) (, ) is a commonly used analytical biochemistry assay, first described by Eva Engvall and Peter Perlmann in 1971. The assay uses a solid-phase type of enzyme immunoassay (EIA) to detect the presence ...

and

RIA A ria (; gl, ría) is a coastal inlet formed by the partial submergence of an unglaciated river valley. It is a drowned river valley that remains open to the sea. Definitions Typically rias have a Drainage system (geomorphology)#Dendritic dr ...

. In this case it is normally quantified by comparing the assays response to a range of similar analytes and expressed as a percentage. In practice,

calibration curve In analytical chemistry, a calibration curve, also known as a standard curve, is a general method for determining the concentration of a substance in an unknown sample by comparing the unknown to a set of standard samples of known concentration. ...

s are produced using fixed concentration ranges for a selection of related compounds and the midpoints (

IC50 The half maximal inhibitory concentration (IC50) is a measure of the potency of a substance in inhibiting a specific biological or biochemical function. IC50 is a quantitative measure that indicates how much of a particular inhibitory substance ...

) 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.

Applications in drug development

Tissue cross-reactivity assay is a standard method based on

immunohistochemistry Immunohistochemistry (IHC) is the most common application of immunostaining. It involves the process of selectively identifying antigens (proteins) in cells of a tissue section by exploiting the principle of antibodies binding specifically to an ...

, 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.

In immunology

In immunology, cross-reactivity has a more narrow meaning of the reaction between an

antibody An antibody (Ab), also known as an immunoglobulin (Ig), is a large, Y-shaped protein used by the immune system to identify and neutralize foreign objects such as pathogenic bacteria and viruses. The antibody recognizes a unique molecule of the ...

and an

antigen In immunology, an antigen (Ag) is a molecule or molecular structure or any foreign particulate matter or a pollen grain that can bind to a specific antibody or T-cell receptor. The presence of antigens in the body may trigger an immune response. ...

that differs from the

immunogen An immunogen is any substance that generates B-cell (humoral/antibody) and/or T-cell (cellular) adaptive immune responses upon exposure to a host organism. Immunogens that generate antibodies are called antigens ("antibody-generating"). Immunogen ...

. It is sometimes also referred to as cross-immunity or cross-protective immunity, although cross-reactivity does not necessarily infer 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. An

adaptive immune response The adaptive immune system, also known as the acquired immune system, is a subsystem of the immune system that is composed of specialized, systemic cells and processes that eliminate pathogens or prevent their growth. The acquired immune system ...

is specific to the antigen that stimulated it (called the immunogen). However, many naturally occurring apparent antigens are actually a mixture of

macromolecule A macromolecule is a very large molecule important to biophysical processes, such as a protein or nucleic acid. It is composed of thousands of covalently bonded atoms. Many macromolecules are polymers of smaller molecules called monomers. The ...

s (for example, from

toxin A toxin is a naturally occurring organic poison produced by metabolic activities of living cells or organisms. Toxins occur especially as a protein or conjugated protein. The term toxin was first used by organic chemist Ludwig Brieger (1849– ...

protein Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residues. Proteins perform a vast array of functions within organisms, including catalysing metabolic reactions, DNA replication, respo ...

s, or

pollen Pollen is a powdery substance produced by seed plants. It consists of pollen grains (highly reduced microgametophytes), which produce male gametes (sperm cells). Pollen grains have a hard coat made of sporopollenin that protects the gametophyt ...

) comprising several

epitope An epitope, also known as antigenic determinant, is the part of an antigen that is recognized by the immune system, specifically by antibodies, B cells, or T cells. The epitope is the specific piece of the antigen to which an antibody binds. The p ...

s. Contact with a complex antigen such as a

virus A virus is a submicroscopic infectious agent that replicates only inside the living cells of an organism. Viruses infect all life forms, from animals and plants to microorganisms, including bacteria and archaea. Since Dmitri Ivanovsky's 1 ...

will stimulate multiple

immune responses An immune response is a reaction which occurs within an organism for the purpose of defending against foreign invaders. These invaders include a wide variety of different microorganisms including viruses, bacteria, parasites, and fungi which could ...

to the virus' different macromolecules as well as the individual epitopes of each macromolecule. For example, the

tetanus Tetanus, also known as lockjaw, is a bacterial infection caused by ''Clostridium tetani'', and is characterized by muscle spasms. In the most common type, the spasms begin in the jaw and then progress to the rest of the body. Each spasm usually ...

toxin is a single protein macromolecular antigen but will stimulate many immune responses due to the

tertiary structure Protein tertiary structure is the three dimensional shape of a protein. The tertiary structure will have a single polypeptide chain "backbone" with one or more protein secondary structures, the protein domains. Amino acid side chains may int ...

of the protein yielding many different epitopes. The

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 for

flu vaccination Influenza vaccines, also known as flu shots, are vaccines that protect against infection by influenza viruses. New versions of the vaccines are developed twice a year, as the influenza virus rapidly changes. While their effectiveness varies fr ...

because of the large number of strains of flu, as antigens produced in response to one strain may confer protection to different strains. Cross-reactivity need not be between closely related viruses, however; for example, there is cross-reactivity between

influenza virus ''Orthomyxoviridae'' (from Greek ὀρθός, ''orthós'' 'straight' + μύξα, ''mýxa'' 'mucus') is a family of negative-sense RNA viruses. It includes seven genera: ''Alphainfluenzavirus'', ''Betainfluenzavirus'', '' Gammainfluenzavirus'', ...

-specific

CD8+ A cytotoxic T cell (also known as TC, cytotoxic T lymphocyte, CTL, T-killer cell, cytolytic T cell, CD8+ T-cell or killer T cell) is a T lymphocyte (a type of white blood cell) that kills cancer cells, cells that are infected by intracellular pa ...

T cells A T cell is a type of lymphocyte. T cells are one of the important white blood cells of the immune system and play a central role in the adaptive immune response. T cells can be distinguished from other lymphocytes by the presence of a T-cell re ...

and

hepatitis C virus The hepatitis C virus (HCV) is a small (55–65 nm in size), enveloped, positive-sense single-stranded RNA virus of the family ''Flaviviridae''. The hepatitis C virus is the cause of hepatitis C and some cancers such as liver cancer ( hepato ...

antigens.

Allergies

Cross reactivity may also occur between a pathogen and a protein found on a non-pathogen (i.e. food.) There may even be cross reactivity between two non-pathogens; for example, Hevein-like protein domains are a possible cause for allergen cross-reactivity between

latex Latex is an emulsion (stable dispersion) of polymer microparticles in water. Latexes are found in nature, but synthetic latexes are common as well. In nature, latex is found as a milky fluid found in 10% of all flowering plants (angiosperms ...

and

banana A banana is an elongated, edible fruit – botanically a berry – produced by several kinds of large herbaceous flowering plants in the genus ''Musa''. In some countries, bananas used for cooking may be called "plantains", distinguis ...

. Cross-reactivity may be caused by identical carbohydrate structures on unrelated proteins from the same or different species. Such

cross-reactive carbohydrate determinants Cross-reactive carbohydrate determinants (CCDs) play a role in the context of allergy diagnosis. The terms CCD or CCDs describe protein-linked carbohydrate structures responsible for the phenomenon of cross-reactivity of sera from allergic patients ...

(CCDs) are an issue in

allergy diagnosis Allergy testing can help confirm or rule out allergies and consequently reduce adverse reactions and limit unnecessary avoidance and medications.Boyce, J ''et al''., "Guidelines for the Diagnosis and Management of Food Allergy in the United States: ...

, where about a fifth of all patients displays

IgE Immunoglobulin E (IgE) is a type of antibody (or immunoglobulin (Ig) " isotype") that has been found only in mammals. IgE is synthesised by plasma cells. Monomers of IgE consist of two heavy chains (ε chain) and two light chains, with the ε c ...

antibodies against Asn-linked oligosaccharides (N-

glycans The terms glycans and polysaccharides are defined by IUPAC as synonyms meaning "compounds consisting of a large number of monosaccharides linked glycosidically". However, in practice the term glycan may also be used to refer to the carbohydrate p ...

) containing core α1,3-linked

fucose Fucose is a hexose deoxy sugar with the chemical formula C6H12O5. It is found on ''N''-linked glycans on the mammalian, insect and plant cell surface. Fucose is the fundamental sub-unit of the seaweed polysaccharide fucoidan. The α(1→3) link ...

. 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.

References

External links

* {{Immune system Chemical reactions Immune system