Antibodies pernicious anemia

Pernicious anemia arises when vitamin B,2 deficiency blocks the metabohsm of folic acid, leading to functional folate deficiency. This impairs erythropoiesis, causing immature precursors of erythrocytes to be released into the circulation (megaloblastic anemia). The commonest cause of pernicious anemia is failure of the absorption of vitamin B,2 rather than dietary deficiency. This can be due to failure of intrinsic factor secretion caused by autoimmune disease of parietal cells or to generation of anti-intrinsic factor antibodies. 

Pernicious anemia is the classical autoimmune disease associated with immunologically mediated injury of the oxyntic mucosa resulting in achlorhydria [52], Parietal cell antibodies are also present in other autoimmune diseases [52, 53] and immunopathies [54] that can be associated with hypo- or achlorhydria. 

Examination of the bone marrow, although important, will only confirm that the hemopoiesis is megaloblastic. A deficiency of folic acid will also cause a megaloblastic anemia and it is not possible to identify the cause on the basis of morphology. A serum assay of both vitamins will usually indicate which is responsible. If the patient is vitamin B12 deficient, the next step is to carry out a vitamin B12 absorption test to confirm that the deficiency is due to a lack of intrinsic factor. Preferably this should not be done until the patient s vitamin B12 and hemoglobin levels have returned to normal, since the gastric and intestinal cells are also affected by a lack of vitamin B12 aborption may be less than optimal if it is attempted too early. Patients with pernicious anemia also have a histamine-fast achlorhydria and gastric atrophy. The disease appears to have an autoimmune basis and antibodies to intrinsic factor can be demonstrated in the serum of more than half of affected patients. 

This condition has often been referred to in the past as juvenile pernicious anemia but it appears to be a quite separate entity. Confusion probably arose because there is a deficiency of intrinsic factor resulting in vitamin B12 malabsorption in both conditions. However, it differs from the disease in adults in that free acid is present in the gastric secretion (A8,L3,M5), the gastric mucosa is usually normal, and antibodies to intrinsic factor are not a feature. Megaloblastic anemia usually develops during the first 2 years of life but this depends on the amount of residual intrinsic factor available, and... 

Patients with severe atrophic gastritis may have impaired absorption of vitamin B12 and a reduced serum level of the vitamin, but this is not accompanied by either megaloblastic anemia or neuropathy. Parietal-cell antibodies have been found in 33% of patients with gastritis, none of these patients having pernicious anemia (12, V4). Intrinsic factor antibodies were not found, and this was not surprising since it is rare to find antibodies to intrinsic factor in the absence of pernicious anemia. Patients with superficial gastritis usually have normal vitamin B12 absorption and normal serum levels of the vitamin. 

Ma, J.Y., Borch, K., Sjostrand, S.E., Janzon, L., Mardh, S. Positive correlation between H,K-adenosine triphosphatase autoantibodies and Helicobacter pylori antibodies in patients with pernicious anemia. Scand J Gastroenterol 29 (1994) 961-965. 

Failure of intrinsic factor secretion is commonly a result of autoimmune disease 90% of patients with pernicious anemia have complement-fixing antibodies in the cytosol of the gastric parietal cells. Similar autoantibodies are found in 30% of the relatives of pernicious anemia patients, suggesting that there is a genetic basis for the condition. 

A number of methods have been developed to permit assessment of folate and vitamin B12 nutritional status and to differentiate between deficiency of the vitamins as a cause of megaloblastic anemia. Obviously, detection of antibodies to intrinsic factor or gastric parietal cells will confirm autoimmune pernicious anemia rather than nutritional deficiency of either vitamin. 

Antibodies to intrinsic factor-active materials from human and hog stomach have been demonstrated in the sera of pernicious anemia patients by Taylor et al. (T9-T12) and Schwartz (S12, S13), and of rabbits immunized with these materials by Lowenstein et al. (L13). Antibody formation in rabbits is species specific, although antibodies have shown some cross-reactions. An antigenic factor common to human and hog material containing intrinsic factor probably produces formation of these antibodies (G75-G75b). 

Circulating antibodies to hog intrinsic factor were also demonstrated in two pernicious anemia patients immunized with purified hog intrinsic factor concentrate (K5). Antibodies developed in their sera, which precipitated hog intrinsic factor in various immune reactions, immobilized it on electrophoresis, and depressed or abolished its enhancing effect upon vitamin B12 absorption in the intestine of other pernicious anemia patients. 

In addition to these, another antibody to intrinsic factor may develop in a certain percentage of pernicious anemia patients, orally treated with hog intrinsic factor concentrate. As shown by Schwartz (S12, S13), this antibody is directed exclusively toward hog intrinsic factor concentrate and not human gastric juice or intrinsic factor derived from the human stomach. Apparently, it causes a topical antibody reaction at the mucosal level, hlocking the promoting action of hog intrinsic factor concentrate on intestinal absorption of vitamin B12 in these pernicious anemia patients. This produces refractoriness to oral treatment with vitamin B12 and hog intrinsic factor concentrate in many pernicious anemia patients (S15). 

A complement-fixing antibody in the serum of pernicious anemia patients, diabetics, and those widi iron-deficiency anemia has been detected against mucosal extracts of the fundus and body of the hmnan stomach and the microsomal fraction of gastric mucosal extracts (D8, 14, M8, M48, RIO, TI3). Immunofluorescent studies have shown that activity is directed against gastric parietal cell cytoplasm (15, RIO, T13) and probably represents another type of antibody, which develops about twice as frequently as the one directed against intrinsic factor in pernicious anemia serum (Fig. 27). 

Thus, in addition to an antibody to the human intrinsic factor or the Bi2-binding principle, another antibody forms in pernicious anemia. 

Fig. 27. Correlation of results of tests for parietal cell and IF antibodies in pernicious anemia patients, showing their independence. The parietal cell antibodies were tested by complement fixation test (CF) while the IF antibodies were assayed by electrophoretic retention test, i.e., immobilization of the intrinsic factor related Bj2 binder on electrophoresis. From Taylor et al. (T13).

Al. Abels, J., Bouma, W., Jansz, A., Woldring, M. G., Bakker, A., and Nieweg, H. O., Experiments on the intrinsic factor antibody in serum from patients with pernicious anemia. /. Lab, Clin. Med. 61, 893-906 (1963). 

J7. Jeffries, C. H., Hoskins, D. W., and Sleisenger, M. H., Antibody to intrinsic factor in serum from patients with pernicious anemia. J. Clin. Invest. 41, 1106-1115 (1962). 

Burman, R, Mardh, S-, Norberg, L., and Karlsson, T, A. (1989). Parietal cell antibodies in pernicious anemia inhibit H,K-adenosine triphosphatase, the proton pump of the stomach. Gffsfrw Pi tcreJegy 96, 1434-1438. 

Vitamin B] deficiency is commonly caused by pernicious anemia (PA). TA is an autoimmune disease resulting from the body s production of antibodies that recognize inlrinsic factor or other proteins of the parietal cell. The binding of antibodies to these proteins results in loss of their function. The parietal cells may be destroyed and be undetectable in patients with PA. The major defect in PA is gastric atrophy. 1 here may be a lack of all gastric secretions, including intrinsic factor, gastric acid, and pepsin. 

Pernicious anemia with a low vitamin B12 concentration and positive intrinsic factor antibodies has been reported in a 54-year-old woman who was receiving interferon alfa as a maintenance treatment for relapsing chronic hepatitis C (219). 

Other potentially useful tests include antibody testing and serum gastrin levels. Positive anti-intrinsic factor antibodies may be present in approximately half of patients with pernicious anemia, but is highly specific for the disease. Additionally, an estimated 85% of patients have anti-parietal cell antibodies, but they are nonspecific, as 3% to 10% of healthy patients have these antibodies. Fasting serum gastrin levels are elevated in more than 70% of patients with cobalamin deficiency and may be useful in assessing patients with borderline... 

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