Monoclonal antibodies specific for the core protein of the beta-subunit of the gastric proton pump (H+/K+ ATPase). An autoantigen targetted in pernicious anaemia.
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The gastric H+/K(+)-transporting adenosine triphosphatase (H+/K+ ATPase) (proton pump) consists of a catalytic alpha-subunit and a recently proposed 60-90-kDa glycoprotein beta-subunit. Using dog gastric membranes as the antigen, we have produced two murine monoclonal antibodies, 4F11 (IgG1) and 3A6 (IgA), which are specific for the 60-90-kDa glycoprotein. The monoclonal antibodies (1) specifically stained the cytoplasm of unfixed and formalin-fixed dog gastric parietal cells; (2) specifically reacted by ELISA with gastric tubulovesicular membranes; (3) recognised epitopes located on the luminal face of parietal cell tubulovesicular membranes, the site of the proton pump, by immunogold electron microscopy; (4) immunoblotted a 60-90-kDa molecule from tubulovesicular membranes and a 35-kDa component from peptide N-glycosidase-F-treated membrane extracts; (5) immunoblotted the 60-90-kDa parietal cell autoantigen associated with autoimmune gastritis and pernicious anemia, purified by chromatography on parietal cell autoantibody- or tomato-lectin-Sepharose 4B affinity columns, and the 35-kDa protein core of this autoantigen; this autoantigen has amino acid sequence similarity to the beta-subunit of the related Na+/K(+)-transporting adenosine triphosphatase (Na+/K+ ATPase) [Toh et al. (1990) Proc. Natl Acad. Sci. 87, 6418-6422]; (6) co-precipitated a molecule of 95 kDa with the 60-90-kDa molecule from 125I-labelled detergent extracts of dog tubulovesicular membranes; and (7) co-purified the catalytic alpha-subunit of the H+/K+ ATPase with the 60-90-kDa molecule by immunoaffinity chromatography of tubulovesicular membrane extracts on a monoclonal antibody 3A6-Sepharose 4B column, indicating a physical association between the two molecules. These results provide further evidence that the 60-90-kDa glycoprotein is the beta-subunit of the gastric H+/K+ ATPase. We conclude that the monoclonal antibodies specifically recognise luminal epitopes on the 35-kDa core protein of the 60-90-kDa beta-subunit of the gastric proton pump, a major target molecule in autoimmune gastritis and pernicious anaemia. These monoclonal antibodies will be valuable probes to study the structure and function of this associated beta-subunit, as well as the ontogeny of the gastric proton pump. (+info)
Is there any relationship between pernicious anemia and iron deficiency?
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INTRODUCTION: Previous studies have suggested that iron deficiency could be due to atrophic gastritis of the body/fundus. The aim of this study was to determine the prevalence of iron deficiency among patients with pernicious anemia and associated factors. PATIENTS AND METHODS: All patients with pernicious anemia diagnosed at our institution between January 1990 and February 2005 were included. Inclusion criteria were: 1- histological diagnosis of atrophic fundic gastritis and 2- criteria of gastric autoimmune involvement. Histology of gastric biopsies was performed in a blinded manner. Iron deficiency was defined as serum ferritin level<15 microg/L in women and<40 microg/L in men. RESULTS: Ninety-five patients (69 women), mean age 60 years (range: 23-90) were included. Twenty patients (21.1%) had normal blood cell counts; 12 patients (12.6%) had microcytosis with or without anemia and 53 patients (55.8%) macrocytosis with or without anemia. Serum ferritin levels were measured in 58 patients, 16 (27.6%) of whom, all women, had iron deficiency. They were significantly younger (39.2 years) than patients without iron deficiency (61.6 years, P<0.0001). Serum gastrin levels did not differ between the groups with and without iron deficiency. A significantly more severe inflammatory infiltrate of the fundus and endocrine cell hyperplasia was observed in iron deficiency patients. Multivariate analysis showed that iron deficiency was linked to female gender and age<50 years. CONCLUSION: Iron deficiency and microcytic anemia are not rare in patients with pernicious anemia and should not rule out the diagnosis. Iron deficiency does not appear to be related to the degree of atrophic fundic gastritis but is linked to female gender and young age, suggesting menstrual blood loss could play a role. Whether decreased iron absorption due to reduced acid secretion favors the expression of gynecological iron loss cannot be ascertained. (+info)
The effect of vitamin B12 on the anemia and combined system disease of addisonian pernicious anemia.
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The effect of the parenteral administration of vitamin B(12) has been observed in eight patients with Addisonian pernicious anemia. Vitamin B(12) in initial doses of 50 micrograms or 25 micrograms induced satisfactory reticulocyte response and a return of erythrocyte count to within normal range in 60 days. In only two of the patients were secondary reticulocyte responses induced on a second injection of vitamin B(12). Concurrently with the hemopoietic response, the bone marrow changed from megaloblastic hyperplasia to normoblastic distribution. The paresthesias associated with combined system disease as well as disturbances in position sense and locomotor function may be entirely relieved or greatly diminished following injections of vitamin B(12). Maintenance injections of vitamin B(12) may be from 30 to 50 micrograms at intervals of one month, the amount depending upon the individual case. Vitamin B(12) may be used without untoward symptoms in patients previously sensitive to liver extract. (+info)
Active B12: a rapid, automated assay for holotranscobalamin on the Abbott AxSYM analyzer.
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Thyroid-associated orbitopathy in patients with Hashimoto's thyroiditis: a case report.
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Thyroid-associated orbitopathy is a set of ophthalmic symptoms resulting from an autoimmune process in which the swelling of extraocular tissues leads to exophthalmos either caused by hypersecretion and accumulation of glycosaminoglycans in the orbit fibroblasts or being the result of inflammatory processes in the oculomotor. These changes cause eyeball motility disturbances, keratopathy, and the pressure on the optical nerve. Thyroid-associated orbitopathy accompanies Graves' disease in most cases, whereas the Hashimoto's disease in only 5%. In the present case, other reasons for the exophthalmos such as tumors of the orbit and sinuses, intracranial tumors, aneurysms and vascular fistulas and orbit tissue inflammation of different etiology were excluded. Additional examinations showed that thyrotropin level was 26 microlU/ml (normal range 0.27-4.0), antithyroglobulin antibody level was 1763 IU/ml (normal range 0-115), antithyrotropin antibody level was 4.93 IU/l (normal range 0-1), and anti-thyroid peroxidase antibody level was 1609 lU/ml (normal range 0-35). An ultrasound examination showed a thyroid gland of 9.8 ml volume. A cytological presentation obtained by thin-needle aspiration biopsy demonstrated inflammatory infiltration of lymphocytes, indicating an autoimmune process. The iodine uptake after 24 hours was 9%. The active form of orbitopathy was diagnosed in the patient with hypothyreosis in the course of Hashimoto's disease. Moreover, the coexistence of another autoimmune disease, pernicious anemia was diagnosed. The administration of the methylprednisolone pulse therapy and levothyroxine caused remission of ophthalmic symptoms, and euthyreosis was obtained. Our report presents a rare coexistence of thyroid orbitopathy and Hashimoto's disease. (+info)
Macrocytosis in multiple sclerosis. A study in 82 de novo Arab patients.
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Macrocytosis, without anaemia, was common in 82 de novo multiple sclerosis patients compared with a similar number of age and sex matched controls. This was an early phenomenon in the course of the disease and was not influenced by the age of the patients nor the duration of the disease. None of the patients proved to have pernicious anaemia, yet the similarity in the geographical and sex distribution as well as the similarity in HLA associations of multiple sclerosis and pernicious anaemia may indicate that both diseases are under similar genetic influence. (+info)
An update on cobalamin deficiency in adults.
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