Radioimmunoassays are used to measure hormones and the technique is based on recognition of an antigen by antibodies largely derived from animal sources. Heterophilic antibodies have been reported to cause interference in 0.050.5% of immunoassays. We present a case in which the presence of heterophilic antibodies led to unnecessary interventions.
A 32 year old gentleman was referred to our centre to localise neuroendocrine tumour. He presented with a history of profuse watery diarrhoea and vomiting associated with RUQ pain. Bloods demonstrated elevated fasting gut hormones: VIP 50 pmol/l (NR 030), Neurotensin 157 pmol/l (NR 0100) and Chromogranin A 72 pmol/l (NR 060). The referring centre was unable to localise neuroendocrine tumour on imaging or at laparotomy. On review the history and fasting gut hormones were consistent with neuroendocrine tumour. Further imaging was performed: MRI abdomen: normal (2) octreotide scan: uptake by gallbladder (3) HIDA scan: suggested a non-functioning gallbladder (4) endoscopic ultrasonography: no pancreatic lesion. He underwent cholecystectomy for presumed neuroendocrine tumour of the gallbladder. Histology demonstrated no neuroendocrine tumour.
The gut hormone radioimmunoassay utilises rabbit antibody and the possibility of interference of the assay was considered. It eluded that he bred rabbits. Two methods were used to prove interference of the assay by the patients anti-rabbit antibodies. One technique used 0.5% non-immune rabbit serum to neutralise the patients antibodies. The second technique used gel chromotography to separate proteins according to molecular weight, separating patient antibodies from gut hormone peptides. Radioimmunoassay was then performed. Using these techniques VIP and Neurotensin were undetectable.
Lessons to be learnt from this case: (1) Consider interfering antibodies particularly if there is a discrepancy between the clinical picture and results (2) The importance of taking a thorough history to include animal exposure.