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Department of Pathology and Laboratory Medicine, University of Pennsylvania, 3400 Spruce St., Philadelphia, PA 19104. Fax 215-662-7529; e-mail larry_kricka{at}path1a.med.upenn.edu
Purpose: The scope and significance of human anti-animal antibody interference in immunological assays is reviewed with an emphasis on human anti-animal 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 noniatrogenic causes and include human anti-mouse, -rabbit, -goat, -sheep, -cow, -pig, -rat, and -horse antibodies and antibodies with mixed specificity. Circulating antibodies can reach gram per liter concentrations and may persist for years. Prevalence estimates for anti-animal antibodies in the general population vary widely and range from <1% to 80%. Human anti-animal antibodies cause interferences in immunological assays. The most common human anti-animal antibody interferent is HAMA, which causes both positive and negative interferences 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 glycolylated, or Fab fragments of antibody agents. Sample pretreatment or assay redesign can eliminate immunoassay interferences caused by anti-animal antibodies. Enzyme immunoassays, immunoradiometric assays, immunofluorescence, and HPLC assays have been designed to detect HAMA and other anti-animal antibodies, but intermethod comparability is complicated by differences in assay specificity and lack of standardization.
Conclusions: Human anti-animal antibodies often go unnoticed, to the detriment of patient care. A heightened awareness on the part of laboratory staff and clinicians of the problems caused by this type of interference in routine immunoassay tests is desirable. Efforts should be directed at improving methods for identifying and eliminating this type of analytical interference.© 1999 American Association for Clinical Chemistry
The following articles in journals at HighWire Press have cited this article:
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A. A.A. Ismail A Radical Approach Is Needed to Eliminate Interference from Endogenous Antibodies in Immunoassays Clin. Chem., January 1, 2005; 51(1): 25 - 26. [Full Text] [PDF]
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P. von Lode, J. Rainaho, and K. Pettersson Quantitative, Wide-Range, 5-Minute Point-of-Care Immunoassay for Total Human Chorionic Gonadotropin in Whole Blood Clin. Chem., June 1, 2004; 50(6): 1026 - 1035. [Abstract] [Full Text] [PDF]
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R. Sapin, A. Agin, and F. Gasser Misleading High Thyrotropin Results Obtained with a Two-Site Immunometric Assay Involving a Chimeric Antibody Clin. Chem., May 1, 2004; 50(5): 946 - 948. [Full Text] [PDF]
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S. Eriksson, M. Junikka, P. Laitinen, K. Majamaa-Voltti, H. Alfthan, and K. Pettersson Negative Interference in Cardiac Troponin I Immunoassays from a Frequently Occurring Serum and Plasma Component Clin. Chem., July 1, 2003; 49(7): 1095 - 1104. [Abstract] [Full Text] [PDF]
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J. F. Emerson, G. Ngo, and S. S. Emerson Screening for Interference in Immunoassays Clin. Chem., July 1, 2003; 49(7): 1163 - 1169. [Abstract] [Full Text] [PDF]
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V. I. Luzzi, M. G. Scott, and A. M. Gronowski Negative Thyrotropin Assay Interference Associated with an IgG{kappa} Paraprotein Clin. Chem., April 1, 2003; 49(4): 709 - 710. [Full Text] [PDF]
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J. S. Krouwer Setting Performance Goals and Evaluating Total Analytical Error for Diagnostic Assays Clin. Chem., June 1, 2002; 48(6): 919 - 927. [Abstract] [Full Text] [PDF]
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J. Bjerner, K. Nustad, L. F. Norum, K. H. Olsen, and O. P. Bormer Immunometric Assay Interference: Incidence and Prevention Clin. Chem., April 1, 2002; 48(4): 613 - 621. [Abstract] [Full Text] [PDF]
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L. J. Kricka Interferences in Immunoassay--Still a Threat Clin. Chem., August 1, 2000; 46(8): 1037 - 1038. [Full Text] [PDF]
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M. Covinsky, O. Laterza, J. D. Pfeifer, T. Farkas-Szallasi, and M. G. Scott An IgM {lambda} Antibody to Escherichia coli Produces False-Positive Results in Multiple Immunometric Assays Clin. Chem., August 1, 2000; 46(8): 1157 - 1161. [Abstract] [Full Text] [PDF]
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A. W. Butch Falsely Increased Values for Rabbit Immunoglobulin-based Nephelometric Immunoassays Attributable to Human Anti-Rabbit Antibodies Clin. Chem., August 1, 2000; 46(8): 1207 - 1208. [Full Text] [PDF]
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S. Eriksson, M. Vehniainen, T. Jansen, V. Meretoja, P. Saviranta, K. Pettersson, and T. Lovgren Dual-Label Time-resolved Immunofluorometric Assay of Free and Total Prostate-specific Antigen Based on Recombinant Fab Fragments Clin. Chem., May 1, 2000; 46(5): 658 - 666. [Abstract] [Full Text] [PDF]
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R. Revelen, A. Bordron, M. Dueymes, P. Youinou, and J. Arvieux False Positivity in a Cyto-ELISA for Anti-Endothelial Cell Antibodies Caused by Heterophile Antibodies to Bovine Serum Proteins Clin. Chem., February 1, 2000; 46(2): 273 - 278. [Abstract] [Full Text] [PDF]
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