Human anti-animal antibody interferences in immunological assays

Purpose: The scope and significance of human anti-animal antibody interfere nce in immunological assays is reviewed with an emphasis on human anti-anim al immunoglobulins, particularly human anti-mouse antibodies (HAMAs). Issues: Anti-animal antibodies (IgG, IgA, IgM, IgE class, anti-isotype, and anti-idiotype specificity) arise as a result of iatrogenic and noniatrogen ic causes and include human anti-mouse, -rabbit, -goat, -sheep, -cow, -pig, -rat, and -horse antibodies and antibodies with mixed specificity. Circula ting antibodies can reach gram per liter concentrations and may persist for years. Prevalence estimates for anti-animal antibodies in the general popu lation vary widely and range from <1% to 80%. Human anti-animal antibodies cause interferences in immunological assays. The most common human anti-ani mal antibody interferent is HAMA, which causes both positive and negative i nterferences in two-site mouse monoclonal antibody-based assays. Strategies to prevent the development of human anti-animal antibody responses include immunosuppressant therapy and the use of humanized, polyethylene glycolyla ted, or Fab fragments of antibody agents. Sample pretreatment or assay rede sign can eliminate immunoassay interferences caused by anti-animal antibodi es. Enzyme immunoassays, immunoradiometric assays, immunofluorescence, and HPLC assays have been designed to detect HAMA and other anti-animal antibod ies, but intermethod comparability is complicated by differences in assay s pecificity and lack of standardization. Conclusions: Human anti-animal antibodies often go unnoticed, to the detrim ent of patient care. A heightened awareness on the part of laboratory staff and clinicians of the problems caused by this type of interference in rout ine immunoassay tests is desirable. Efforts should be directed at improving methods for identifying and eliminating this type of analytical interferen ce. (C) 1999 American Association for Clinical Chemistry.