INTERFERENCE IN IMMUNOASSAYS FROM HUMAN ANTI-ANIMAL ANTIBODIES

Where the results of measurements performed by immunoassays do not fit the clinical picture, the possibility must be considered that there is interference in the test method from human anti-animal antibodies (HAAA) circulating in the patient’s plasma. There have been occasional reports over many years of this problem (recently reviewed by Ismail and Barth (2001) and by Kricka (1999) which can affect both the more recent automated two-site immunoassays as well as the older radioimmunoassays and can result in both artefactually high and artefactually low results being reported. The general impression given by the literature is that the two-site assays are more susceptible but a recent report showed that it is possible for even multiple radioimmunoassays to be affected by the plasma from one patient (Park et al. 2003).

It is thought that 30-40% of the population have circulating HAAA (Ismail and Barth 2001) and although in most cases the HAAA are not of sufficient concentration, specificity or affinity to cause noticeable interference in assay methodology, it seems that 0.5% or more of immunoassay results could be significantly affected (Ismail and Barth 2001). In one thyroglobulin assay, 1.5-3% of specimens exhibited significant interference (Preissner et al. 2003). Serious consequences, including unnecessary chemotherapy and surgery, have on occasion followed from spurious immunoassay results due to HAAA.

Whenever there appears to be a discrepancy between clinical findings and immunoassay results, the laboratory should be informed since it can usually test the specimen for the presence of interference by one or two of several methods. These include dilution, PEG extraction, addition of non-immune animal sera or measurement by a different method.

Ismail AAA, Barth JH. BMJ 323:706-7 (2001)

Kricka LJ. Clin. Chem. 45:942-56 (1999)

Park A, Edwards M, Donaldson M, Chatei M, Meeran K. BMJ. 326:541-2 (2003).

Preissner C, O’Kane DJ, Ravinder JS, Morris JC, Grebe SKG. JCEM 88:3069-74 (2003).