Interference from Human Anti Animal Antibody

Human anti-animal antibodies (HAAAs) are different from heterophilic antibody by their specificity to antibody from certain species and by their stronger avidity. HAAAs arise mostly when the patient is exposed to a defined animal antigen. In the majority of the cases, the exposure is from diagnostic (i.e., tumor-targeted imaging agent) or therapeutic applications of tumor-specific monoclonal antibodies. Examples of animal-derived pharmaceuticals which may contain anti-animal antibody are given in Table 1.

Table 1

Animal-Derived Pharmaceuticals

Table 1

Animal-Derived Pharmaceuticals


Source animal


Antibody-targeted imaging agents

Mouse, rat

(8), (9)

Antibody-targeted drugs

Mouse, rat

(10), (10)

Anti-thymocyte globulin

Horse, rabbit

(11), (12)




Digibind (anti-digoxin Fab)



Factor VIII





(16), (17)


Rabbit, chicken

(18), (19)

Patent medicines



Anti-animal antibodies may also arise from contact with the animals (e.g., animal husbandry or keeping of animals as pets) (21) and the transfer of dietary antigens across the gut wall in conditions such as celiac disease (22).

Serum concentrations of HAAA may range from microgram to gram per liter. The HAAA may be transient, lasting a few days to months and sometimes even years. Sometimes it is difficult to validate whether a particular interference in an assay is from HAAA especially if the presence of antibody in the patient is transient (23). The prevalence of HAAA, especially human anti-mouse antibody (HAMA), may vary from <1% up to 80% among hospitalized patients or outpatients depending on the population studied. Several commercial assay kits for HAMA estimation are available but a negative result may also be observed even if HAMA is present due to its heterogeneous nature (24)

HAMA interferes in immunoassays that use murine antibodies to the analyte. As more and more monoclonal (most common source is mouse) antibodies are used in commercial and other immunoassays (because of the specificity of the antibody and the reliability of the antibody supply), impact of HAMA interference in terms of incorrect result and resulting inaccuracy in diagnosis and therapy has become more serious. As expected, the HAMA can be of varied prevalence, specificity, titer, and binding capacity. The most common HAMA concentration is <10 ^g/mL, however HAMA concentration as high as 1000 ^g/mL has been reported. As HAMA arises from exposure of patients to mouse antibodies, cancer patients who may have used such antibodies as part of imaging or therapeutic agents have higher prevalence of HAMA occurrences (40-70%). HAMA can be IgG (most common), IgM, IgA, or IgE and can be directed to any part of the monoclonal antibody used in the assay (Fc, Fab, idiotope, and so on).

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