INADEQUATE RESPONSE TO H-2-RECEPTOR ANTAGONISTS - ABSENCE OF PARIETAL-CELL CAMP-STIMULATING AUTOANTIBODIES

In peptic ulcer patients with adequate (AR; N = 16) and inadequate res ponse (IR; N = 20) to H-2-receptor antagonists, the presence of pariet al cell cAMP-stimulating autoantibodies was studied. Serum Ig fraction s from these patients and 10 control subjects were examined to test wh ether they could stimulate cAMP production in a gastric cell line mode l. The human cell line HGT-1 was found to be a sensitive in vitro mode l for the cAMP stimulation assay as histamine (10 mu M) increased by 1 1-fold the production of cAMP. Neither IgG (4 mg/ml) nor IgG-free Ig f ractions (1 mg/ml) isolated from the blood of AR or IR affected cAMP p roduction in the HGT-1 cells. The results obtained with the cAMP stimu lation assay were confirmed by indirect immunofluorescence measurement s based on frozen sections of rat stomach and kidney. No specific stai ning of rat parietal cells could be observed with patient sera. In add ition, human gastric biopsies of the oxyntic mucosa from the same pati ents were studied for immunoreactive cell populations to assess organ- specific autoimmune processes. Biopsy specimens from AR and IR showed increased lymphocytic infiltrates, usually associated with gastritis. However, no significant differences in location of various cell popula tions between AR and IR could be observed. Our findings do not support a recent hypothesis that poor response to treatment with H-2-receptor antagonists is due to the presence of autoantibodies.