ABSENCE OF A GASTRIN INHIBITORY FACTOR IN THE IGG FRACTION OF SERUM FROM PATIENTS WITH PERNICIOUS-ANEMIA

Patients with Addisonian pernicious anaemia are alleged to generate antibodies directed against the gastrin receptor. We purified IgG from 15 patients with pernicious anaemia and 15 healthy controls in an effort to show attenuation of gastrin specific binding in vitro and inhibition of gastrin stimulated acid secretion in vivo. Binding of the IgG fraction was determined in a radioreceptor assay utilising the rat pancreatic carcinoma cell line AR42J which expresses high affinity gastrin binding sites (K(d) = 5x10-10). In comparison with control serum, there was no significant displacement (p = 0.10) of human gastrin-17 binding by pernicious anaemia samples at either 0.3 mg protein/ml (control (mean (SEM)) 1489 (131) cpm; patients 1858 (174) cpm) or 3 mg protein/ml (control 1930 (110); patients 2195 (107) cpm). The effect of intravenous and intragastric IgG on acid secretion in the anaesthetised rat was determined over a 60 minute period after stimulation with 1 μg/kg human gastrin-17. A bolus injection of IgG (60-200 mg/kg) had no significant effect (p = 0.50) on gastrin stimulated acid output (29.21 (1.28) μmol H+/h) compared with control (27.48 (4.70) μmol H+/h). Similarly, instillation of 800 mg/kg IgG directly into the stomach for 90 minutes also failed to influence gastrin stimulated acid output (29.69 (3.22) μmol H+/h). Thus, we have been unable to confirm previous reports of an IgG from patients with pernicious anaemia capable of blocking gastrin receptor binding or gastrin stimulated acid secretion.