Decreased Gastrin Secretion in Patients W Ith Late-onset Hypogammaglobulinemia

We undertook this study to determine whether patients with late-onset hypogammaglobulinemia, who are at very high risk for gastric cancer, have a reduced secretion of gastrin after stimulation with food or bombe­ sin, a potent gastrin-releasing stimulus. We compared the plasma gastrin responses to bombesin and to a standard test meal in 18 patients with late-onset hypogammaglob­ ulinemia with those in patients with X-linked agamma­ globulinemia, early-onset hypogammaglobulinemia, or hy­ pogammaglobulinemia due to lymphoproliferative cancer, and in 30 normal control subjects. Thirteen of 18 patients with late-onset hypogammaglob­ ulinemia (72 percent) had an abnormally low gastrin response to bombesin, as compared with none of 21 patients with other forms of hypogammaglobulinemia HYPOGAMMAGLOBULINEMIA comprises a heterogeneous group of immunodeficiency dis­ orders. 1,2 O f the congenital forms, X-linked agamma­ globulinemia has been studied the most thoroughly and is characterized by an absence of B lymphocytes in the bone marrow, peripheral blood, and lymphoid tissues.3,1 There are other forms of early-onset hypo­ gammaglobulinemia, but differentiating them from isolated forms of X-linked agammaglobulinemia or from early manifestations of late-onset hypogamma­ globulinemia is difficult. When primary hypogamma­ globulinemia develops later in life, the diagnosis of late-onset hypogammaglobulinemia (also called com­ mon variable immunodeficiency) is clear.J,b In paFrom the Departments o f Gastroenterology-Hepatology (G .d .H ., J .B .M .J .J . , C .B .H .W .L .) and Infectious Diseases (J .W .M .v .d .M ., R .v .F .), University Hos­ pital, Leiden, The Netherlands. Address reprint requests to Dr. Laniers at the Department of Gastroenterology-Hepatology, University Hospital o f Leiden, Bldg. I. C4-P, P.O. Box 9600, 2300 RC Leiden, The Netherlands. Supported by a grant (IK W 83-11) from the Netherlands Cancer Foundation (Koningin Wilhelmina Fonds). (P<0.05). After a test meal, abnormally low gastrin secre­ tion was found in 6 of 14 patients with late-onset hypo­ gammaglobulinemia (43 percent) and in 1 of 18 patients with other forms of the disease (6 percent) (P not sig­ nificant). The plasma gastrin responses to stimulation with bom­ besin or food distinguished late-onset hypogammaglobu­ linemia from other forms, with sensitivities of 72 and 43 percent and specificities of 100 and 94 percent, respec­ tively. Stimulated gastrin response can therefore be used as a marker for this type of immunodeficiency. The test responses also showed heterogeneity among patients with late-onset hypogammaglobulinemia and may help to identify patients with an increased risk for gastric cancer. (N Engl J Med 1988; 318:1563-7.) tients with late-onset hypogammaglobulinemia, B lymphocytes are usually present, but they do not dif­ ferentiate into plasma cells/ This humoral immuno­ deficiency is often accompanied by abnormalities in the T lymphocytes. The disease has been classified as a combined immunodeficiency disorder by the World J 4 Health Organization.(> The cellular immune defects accompanying late-onset hypogammaglobulinemia are by no means constant or homogeneous, and it re­ mains uncertain whether late-onset hypogammaglob­ ulinemia represents a single entity.7' 10 Low serum concentrations of gammaglobulin can occur not only in primary forms of hypogammaglobulinemia but also in hematologic cancer or intestinal or renal disease (as a result of loss of protein) . 11 In addition to an increased susceptibility to infec­ tion, patients with primary hypogammaglobulinemia often have abnormalities of the gastrointestinal tract, including malabsorption, lymphonodular small-intes­ tinal hyperplasia, pernicious anemia, and gastric cancer 5,12-23 These gastrointestinal disorders have been 1564 THE NEW ENGLAND JOURNAL OF MEDICINE June 16, 1988 reported mainly in patients with late-onset hypogammaglobulinemia,D’l4’24’2:> but recent studies indicate that patients with other types of hypogammaglobulin­ emia may also have such abnormalities. 15?26 Patients with late-onset hypogammaglobulinemia have a 50fold increase in the incidence of stomach cancer.2' Patients with the intestinal type of gastric cancer have a reduced plasma gastrin response to the gastrinreleasing peptide bombesin.28 We therefore studied plasma gastrin secretion during bombesin infusion in patients with various forms of hypogammaglobuline­ mia to determine whether such patients have abnor­ malities in gastrin secretion after stimulation and whether those abnormalities are speciiic to subgroups of patients with hypogammaglobulinemia. Since bom­ besin is not readily available, we also measured post­ prandial plasma gastrin levels to determine whether bombesin can be replaced by a meal as a stimulant of gastrin secretion.