Autoantibodies to gastrin in patients with pernicious anaemia--a novel antibody.
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Autoantibodies arise when there is a breakdown in immunological tolerance. Autoantibodies to parietal cells and intrinsic factor are found in autoimmune atrophic gastritis (AAG) and are associated with elevated plasma gastrin. Endogenous gastrin autoantibodies have not been described to date. The aim of this study was to investigate the occurrence of autoantibodies to gastrin. Plasma from 50,000 patients, including more than 2000 with AAG, was tested. Gastrin was measured by radioimmunoassay (RIA) in whole plasma and the presence of autoantibody determined by using a control which omitted assay antibody. The quantity and affinity of gastrin autoantibodies was assessed. Three patients had autoantibodies to gastrin. All three had AAG and pernicious anaemia (PA). The antibodies were of low titre and relatively high affinity. Free circulating plasma gastrin levels were within the normal range, but total gastrin levels were elevated. This is the first description of autoantibodies to endogenous gastrin. The incidence of antibodies to gastrin is low, they are found in association with PA, and they may lead to falsely low measurements of plasma gastrin. (+info)
Potential difference across the normal and the abnormal gastric mucosa in man.
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The mucosal potential difference in the body of the stomach was measured in 18 patients with gastric ulcers, five with gastritis, and three with pernicious anaemia. The results were compared with those of 12 normal volunteers. Significantly lower than normal levels were found in the groups of patients with gastric ulcers and gastritis. The patients with pernicious anaemia had even lower potential differences. In an additional 25 subjects, measurements were made in the duodenal bulb and at five sites in the stomach under direct vision at endoscopy. Biopsies were taken from each site for histology. Subjects with gastritis at the high lesser curve had a significantly lower potential difference at that site than those without gastritis. In the latter group, the potential difference at the high lesser curve was as low as in the antrum, and invariably lower than at the high greater curve. (+info)
Immunomodulation by vitamin B12: augmentation of CD8+ T lymphocytes and natural killer (NK) cell activity in vitamin B12-deficient patients by methyl-B12 treatment.
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It has been suggested that vitamin B12 (vit.B12) plays an important role in immune system regulation, but the details are still obscure. In order to examine the action of vit.B12 on cells of the human immune system, lymphocyte subpopulations and NK cell activity were evaluated in 11 patients with vit.B12 deficiency anaemia and in 13 control subjects. Decreases in the number of lymphocytes and CD8+ cells and in the proportion of CD4+ cells, an abnormally high CD4/CD8 ratio, and suppressed NK cell activity were noted in patients compared with control subjects. In all 11 patients and eight control subjects, these immune parameters were evaluated before and after methyl-B12 injection. The lymphocyte counts and number of CD8+ cells increased both in patients and in control subjects. The high CD4/CD8 ratio and suppressed NK cell activity were improved by methyl-B12 treatment. Augmentation of CD3-CD16+ cells occurred in patients after methyl-B12 treatment. In contrast, antibody-dependent cell-mediated cytotoxicity (ADCC) activity, lectin-stimulated lymphocyte blast formation, and serum levels of immunoglobulins were not changed by methyl-B12 treatment. These results indicate that vit.B12 might play an important role in cellular immunity, especially relativing to CD8+ cells and the NK cell system, which suggests effects on cytotoxic cells. We conclude that vit.B12 acts as an immunomodulator for cellular immunity. (+info)
The rise in circulating gastrin with age is due to increases in gastric autoimmunity and Helicobacter pylori infection.
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To assess the effect of increasing age on circulating gastrin, we surveyed serum gastrin, Helicobactor pylori seroantibody status and gastric autoimmunity in 366 hospitalized patients aged 15-90 years. Data were subjected to multivariate analysis, using logarithmic transformation to normalize the distribution of gastrin concentrations (presented as geometric means and 95% CIs). The frequency of H. pylori-positive antibody status increased with age from 28% in the second decade to > 70% beyond the fourth decade. Fasting gastrin concentrations rose significantly from 44 ng/l (41-48) in the second decade to 95 ng/l (67-131) by the eighth decade (p = 0.001) in the total group. Twenty-seven patients (6.8% of the total) tested positive for gastric auto-antibodies: 2% of patients in the second decade, rising to 15.9% in the eighth decade. These patients formed a distinct group with respect to circulating gastrin concentrations. Excluding these 27, fasting gastrin concentrations still rose significantly, from 44 ng/l (41-48) in the second decade, to 67 ng/l (50-89) in the eighth decade (p = 0.003) in the remaining 341 patients. Fasting gastrin concentrations were significantly higher in patients who were H. pylori-seropositive (59 ng/l, 54-64 vs. sero-negative 41 ng/l, 37-46) (p = 0.002), and there was no increase in circulating gastrin concentrations with increasing age in either the H. pylori-positive or the H. pylori-negative group. The increase in circulating fasting gastrin observed with increasing age is due to an increased incidence of gastric antibodies associated with auto-immune atrophic gastritis, and an increased incidence of H. pylori infection. (+info)
Thyrogastric autoimmune disease. Studies on the cell-mediated immune system and histocompatibility antigens.
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Cell-mediated immune responses were studied in autoimmune diseases of thyrogastric type, Hashimoto's thyroiditis and autoimmune pernicious anaemia-type gastritis. Specific cell-mediated immunity was investigated by the leucocyte migration inhibition procedure, and general cell-mediated immunity (T-cell performance) was studied by standard in vivo and in vitro tests. In thyrogastric autoimmune diseases inhibition of migration of leucocytes was induced by thyroglobulin and gastric parietal cell microsomes; under conditions of presumably low cellular sensitization, stimulation of migration was observed. There was no depression of general cell-mediated immunity, in contrast to what occurs in systemic lupus erythematosus and related autoimmune diseases. A weak association of autoimmune gastritis with HL-A3 and HL-A7 (P LESS THAN 0.05) lost significance when an appropriate correction was applied; this weakness with HL-A clearly does not explain the strong genetic component in thyroid and gastric autoimmunity. (+info)
Measles antibodies and autoantibodies in autoimmune disorders.
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Measles CF antibodies have been examined in the sera of patients with a variety of clinical disorders associated with the production of autoantibodies. Previous reports of high-titre reactions in DLE and chronic active hepatitis have been confirmed, the titres in the latter disorder being particularly elevated. Mean antibody titres to measles in patients with rheumatoid arthritis were significantly lower than in matched controls, and an inverse correlation between measles antibody levels and serum globulin levels was found. Measles antibody titres in patients with myasthenia gravis and primary biliary cirrhosis did not differ significantly from those found in controls. However, subdivision of patients with rheumatoid arthritis, myasthenia gravis and primary biliary cirrhosis showed that the presence of anti-nuclear antibody (ANA) was associated with significantly increased measles antibody levels compared with the ANA-negative sera. The presence of gastric parietal cell antibody or thyroid microsomal antibody did not appear to be associated with increased measles antibody levels, whether or not they occurred in association with previous anaemia or thyroid disease. Possible explanations for these findings in terms of immune complex formation and immune hyper-reactivity are discussed. (+info)
Serum leptin levels in patients with sideropenic and pernicious anemia: the influence of anemia treatment.
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Leptin is a 16 kDa protein hormone involved in food intake, energy expenditure regulation and numerous other physiological processes. Recently, leptin has been demonstrated to stimulate hematopoietic stem cells in vitro. The aim of our study was to measure serum leptin and erythropoietin levels in patients with sideropenic (n = 18) and pernicious anemia (n=7) before and during anemia treatment. Blood samples for the blood count, leptin and erythropoietin determinations were obtained by venepunction at the time of the diagnosis of anemia and after partial and complete anemia recovery. The relationships of serum leptin levels to erythropoietin levels and blood count parameters were also studied. No significant differences in serum leptin levels between the groups studied were found. The serum leptin levels in none of groups were modified by treatment of anemia (basal levels, the levels during treatment and after anemia recovery were 13.1+/-14.5 vs 12.8+/-15.6 vs 12.0+/-14.8 ng/ml in patients with sideropenic anemia and 7.8+/-8.5 vs 9.5+/-10.0 vs 8.9+/-6.6 ng/ml in patients with pernicious anemia). The erythropoietin levels were higher at the time of anemia in both groups and decreased significantly after partial or complete recovery. Serum leptin levels in both groups correlated positively with the body mass index. No significant relationships were found between serum leptin levels and erythropoietin values or various parameters of the peripheral blood count. We conclude that serum leptin levels in patients with sideropenic and pernicious anemia positively correlate with the body mass index but are not influenced by the treatment of anemia. (+info)
Screening for hypothyroidism in elderly inpatients.
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Routine biochemical screening for hypothyroidism in 2000 geriatric inpatients proved valuable and practicable and yielded 46 cases (2.3%). A non-specific clinical picture was particularly common, with less than a third of the cases showing "typical" signs and symptoms. Psychiatric manifestations, especially depression, were important and frequent and responded well to thyroxine. There was a preponderance of female cases of hypothyroidism and a strong association with other autoimmune diseases, notably pernicious anaemia and rheumatoid arthritis. (+info)