A Radical Approach Is Needed to Eliminate Interference from Endogenous Antibodies in Immunoassays

Interference in immunoassays by circulating endogenous antibodies is as old as the technique itself. Its mechanisms have remained poorly studied, however, and its detrimental effects are underestimated despite numerous reports highlighting its serious consequences (1)(2)(3)(4)(5)(6)(7)(8)(9). One reason for this situation is that immunoassays are moving targets. Assay protocols and reagents, even from the same provider and for the same analyte, may change every few years. Even when research on a method is published, it may be perceived as method-dependent and obsolete by the time of publication as the technique may have been altered in the interim.Defining the precise mechanisms of interference by endogenous antibodies has been challenging because of variation in the phenomena produced by the antibodies. Endogenous antibodies may increase readings in some assays but decrease the results in others (4)(5). Interfering antibodies may be identified by nonlinearity in some assays but show perfect linearity on serial dilution in others (5). Interference from some antibodies may be blocked by commercially available “blocking reagents”, but interferences from other antibodies are not (5). Repeat analyses by other methods may identify samples with interfering antibodies, with the comparison assay yielding gross disparity, but in other cases good agreement may be seen between two methods (4)(5).The purpose of this report is to attempt to highlight some of the potential underlying mechanisms of interference from endogenous antibodies and to show that these mechanisms suggest that this interference is and will remain an insidious, variable, and unpredictable problem. This is …