Digestive Diseases and Sciences, Vol. 40. No. 7 (July 1995). pp. 1538-1541 Natural Killer Cell Activity in Patients with Pernicious Anemia J.A. VARGAS, MD, PhD, M. ALVAREZ-MON, MD, PhD, L. MANZANO, MD, PhD, A. ALBILLOS, MD, PhD, A. FERNANDEZ-CORUGEDO, MD, J.C. GEA-BANACLOCHE, MD, F.M. GONZALEZ, MD, PhD, and A. DURANTEZ, MD, PhD Patients with pernicious anemia have an estimated risk of gastric adenocarcinoma that ranges from three- to fivefold greater than that of the general population. It has been reported that NK cells may be involved in immunosurveillance against tumor spread. The natural killer cell activity of peripheral blood mononuclear cells was analyzed in 22 patients with pernicious anemia and in 19 healthy controls. Levels of natural killer cell activity against K-562 target cells were similar in control subjects and patients, regardless of gastrin levels and time elapsed since diagnosis. According to quantitative flow cytometry analysis, similar percentages of phenotypically defined NK cells (CD16 +) were found in peripheral blood mononuclear cells from patients and healthy controls. Our results show that in pernicious anemia patients, the percentage of NK cells present in peripheral blood mononuclear cells and their lytic activity are normal. KEY WORDS: NK cell; pernicious anemia: immunology: gastric adenocarcinoma. Gastric adenocarcinoma is three to five times more frequent among patients with pernicious anemia than among the general population (1-3). A recent popu- lation-based study suggested an increased prevalence of carcinomas of stomach, esophagus, pancreas, and rectum in patients with pernicious anemia (1). There is also an increase in carcinoid tumors and argyrophil- cell hyperplasia, possibly related to the hypergastrine- mia found in pernicious anemia (4, 5). Natural killer (NK) cells are thought to participate actively in immunosurveillance against tumor dissem- ination (6, 7). Several studies have found diminished Manuscript received November 22, 1994; revised manuscript received February 17, 1995; accepted March 27, 1995. From the Services of Internal Medicine I and Gastroenterology, Department of Medicine, Clfnica Puerta de Hierro, Universidad Aut6noma, Madrid; and Service of Internal Medicine, Department of Medicine, Hospital Universitario Principe de Asturias, Univer- sidad de Alcahi de Henares, Madrid, Spain. This work was partially supported by grants from the Comisi6n Interministerial de Ciencia y Tecnologfa (SAF93-1191) and Fun- dacidn LAIR, Spain. Address for reprint requests: Dr. J. A. Vargas, Servicio de Me- dicina Interna I, Clinica Puerta de Hierro. C/San Martin de Porres 4, 28035 Madrid. Spain. NK activity in peripheral blood mononuclear cells of patients with malignant neoplasms (8-10). This de- fect may be a direct result of the tumor itself or, alternatively, may represent a risk factor for the de- velopment of cancer. Few studies have assessed NK activity in subjects with increased risk of developing a neoplasm (11-14). Our objective was to measure the number of NK cells and the amount of NK activity in peripheral blood mononuclear cells (PBMC) of patients with perni- cious anemia and compare them with those of a control group of similar age and sex. To the best of our knowledge, this is the first published work to deal with NK activity in pernicious anemia. MATERIALS AND METHODS Patients. We studied 22 patients with pernicious anemia (16 women, 6 men), with a mean age of 73.3 years (range: 58-87 years). Diagnosis of pernicious anemia required the presence of megaloblastosis in peripheral blood or bone marrow, diminished plasma B12 (<300 pg/ml), an abnormal Schilling test that normalized with the administration of 1538 Digestive Diseases and Sciences, VoL 40, No. 7 (Jalv 1995) 0163-2116/95/0700-1538507.50/0 .r 1995PlenumPublishing Corporation