Abstract
In peptic ulcer patients with adequate (AR;N=16) and inadequate response (IR;N=20) to H2-receptor antagonists, the presence of parietal cell cAMP-stimulating autoantibodies was studied. Serum Ig fractions from these patients and 10 control subjects were examined to test whether they could stimulate cAMP production in a gastric cell line model. The human cell line HGT-1 was found to be a sensitivein vitro model for the cAMP stimulation assay as histamine (10 μM) increased by 11-fold the production of cAMP. Neither IgG (4 mg/ml) nor IgG-free Ig fractions (1 mg/ml) isolated from the blood of AR or IR affected cAMP production in the HGT-1 cells. The results obtained with the cAMP stimulation assay were confirmed by indirect immunofluorescence measurements based on frozen sections of rat stomach and kidney. No specific staining of rat parietal cells could be observed with patient sera. In addition, human gastric biopsies of the oxyntic mucosa from the same patients 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 populations between AR and IR could be observed. Our findings do not support a recent hypothesis that poor response to treatment with H2-receptor antagonists is due to the presence of autoantibodies.
Similar content being viewed by others
References
Kirk RM: Autoimmunity in peptic ulceration. Biomed Pharmacother 43:571–572, 1989
Dobi S, Petranyi GY: Secretagoue globulins in the blood of duodenal ulcer patients. Acta Med Acad Sci Hung 33:205–210, 1973
Dobi S, Lenkey B: Role of secretagogue immunoglobulin in gastric acid secretion. Acta Physiol Acad Sci Hung 60:9–25, 1982.
De Lazzari F, Mirankian R, Hammond L, Venturi C, Naccarato R, Bottazzo GF: Gastric cell cAMP stimulating autoantibodies in duodenal ulcer disease. Gut 29:94–100, 1988
Adams DD, Purves HD: Abnormal response in the assay of thyrotropin. Proc Univ Otago Med School 34:11–12, 1965
Mittag T, Kornfeld P, Tormay A, Woo C: Detection of antiacetylcholine receptor factors in serum and thymus from patients with myasthenia gravis. N Engl J Med 294:691–694, 1976
Flier JS, Kahn CR, Roth J, Bar RS: Antibodies that impair insulin receptor binding in an unusual diabetic syndrome with severe insulin resistence. Science 190:63–65, 1975
Fraser CM, Venter JC, Kaliner M: Autonimic abnormalities to beta-adrenergic receptors. N Engl J Med 305:1165–1170, 1981
Burman P, Mardh S, Lööf L, Naesdal J, Karlson FA. Peptic ulcer disease: Absence of antibodies stimulating the histamine sensitive adenylate cyclase of gastric mucosa cells. Gut 32:620–623, 1991
Walker S, Krishna DR, Klotz U, Bode JC: Frequent nonresponse to histamine H2-receptor antagonists in cirrhotics. Gut 30:105–109, 1989
Backer ET, Harff GA: Antibodies to lactate dehydrogenase in serum identified by use of immobilized protein G and immobilized jacalin, a jackfruit lectin. Clin Chem 35:2190–2195, 1989
Laboisse CL, Augeron C, Couturier-Turpin M-H, Gespach C, Cheret A-M, Potet F. Characterization of a newly eastablished human gastric cancer cell line HGT-1 bearing histamine H2-receptors. Cancer Res 42:1541–1548, 1982
Sarem-Aslani A, Ratge D, Bigge H-H, Walker S, Klotz U, Wisser H: A method to assess histamine-induced cyclic AMP production in isolated gastric mucosal cells from human biopsies. Pharmacology 42:327–332, 1991
Henry B (editor), Zweimann B, Lisak RP: Autoantibodies: Autoimmunity and immune complex.In Clinical Diagnosis and Management by Laboratory Methods. Philadelphia, WB Saunders, 1984, pp 924–954
Hsu SM, Raine L, Fanger H: The use of antiavidine antibody and avidin-biotin complex in immunoperoxidase technics. Am J Clin Pathol 75:816–821, 1981
Fritz P, Müller J, Wegner G, Braun U, Gran A, Tuczek HV, Moessner E, Schenk R: Immunhistochemie: Theoretische Möglichkeiten, praktisch Anwendungen. Zentralblt Allg Pathol Pathol Anat 130:187–193, 1985
Emami S, Gespach C: Pharmacology of histamine H2-receptor antagonists in the human gastric cancer cell line HGT-1. Biochem Pharmacol 35:1825–1834, 1986
Fagot E, Emami S, Chastre E, Bawab W, Gespach C: Pharmacological control of the histamine H2-receptor-adenylate cyclase system by famotidine and ranitidine in normal and cancerous human gastric epithelia. Agents Actions 23:293–296, 1988
Gugler R, Rohner H-G, Somogyi AA: Therapieversager unter Cimetidin beim Ulcus duodent. DMW 107:1054, 1982
Jones DB, Howden CW, Burget DW, Kerr GD, Hunt RH: Acid suppression in duodenal ulcer: A meta-analysis to define optimal dosing with antisecretory drugs. Gut 28:1120–1127, 1987
Burget DW, Chiverton SG, Hunt RH: Is there an optimal degree of acid supression for healing of duodenal ulcers? Gastroenterology 99:345–351, 1990
McIsaac RL, Dixon JS, Mills JG, Wood JR: Ranitidine in the treatment of duodenal ulcer disease: Relationship between antisecretory effect and ulcer healing rate. Aliment Pharmacol Ther 5:227–243, 1991
Masala C, Sumurra G, Di Prima MA, Amedndolea MA, Celestino D, Salsano F: Gastric parietal cell antibodies: Demonstration by immunofluorescence of their reactivity with the surface of the gastric parietal cells. Clin Exp Immunol 41:271–280, 1980.
Spencer JO, Finn T, Isaacson A: Expression of HLA-DR antigens on the epithelium associated with lymphoid tissue in the human gastrointestinal tract. Gut 27:153–157, 1986
Collen MJ, Stanzak VJ, Ciarleglio CA: Refractory duodenal ulcers: Nonhealing duodenal ulcers with standard doses of antisecretory medication. Dig Dis Sci 34:233, 1989
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Bergmann, C., Sarem-Aslani, A., Ratge, D. et al. Inadequate response to H2-receptor antagonists. Digest Dis Sci 40, 2678–2683 (1995). https://doi.org/10.1007/BF02220460
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF02220460