1/10. Erythroblastic synartesis: an auto-immune dyserythropoiesis.Erythroblastic synartesis is a rare form of acquired dyserythropoiesis, first described by Breton-Gorius et al in 1973. This syndrome is characterized by the presence of septate-like membrane junctions and "glove finger" invaginations between erythroblasts, which are very tightly linked together. This phenomenon, responsible for ineffective erythropoiesis, leads to an isolated severe anemia with reticulocytopenia. In the following report, we describe 3 new cases of erythroblastic synartesis associated with dysimmunity and monoclonal gammapathy. In all cases, the diagnosis was suggested by characteristic morphological appearance of bone marrow smears, and further confirmed by electron microscopy. Ultrastructural examination of abnormal erythroblast clusters showed that these cells were closely approximated with characteristic intercellular membrane junctions. The pathogenesis of the dyserythropoiesis was modeled in vitro using crossed erythroblast cultures and immunoelectron microscopy: when cultured in the presence of autologous serum, the erythroblasts from the patients displayed synartesis, whereas these disappeared when cultured in normal serum. Moreover, synartesis of normal erythroblasts were induced by the patient IgG fraction. Immunogold labeling showed that the monoclonal IgG were detected in, and restricted to, the synartesis. A discrete monoclonal plasmacytosis was also found in the patient bone marrow. The adhesion receptor CD36 appeared to be concentrated in the junctions, suggesting that it might be involved in the synartesis. These experiments indicated that a monoclonal serum immunoglobulin (IgG in the present cases) directed at erythroblast membrane antigen was responsible for the erythroblast abnormalities. Specific therapy of the underlying lymphoproliferation was followed by complete remission of the anemia in these cases.- - - - - - - - - - ranking = 1keywords = antigen (Clic here for more details about this article) |
2/10. Congenital dyserythropoietic anaemia type II: a case study.A 13-year-old girl with chronic anaemia showed features of congenital dyserythropoietic anaemia (CDA) type II. The main clinical and haematological findings were splenomegaly, a mild microcytic anaemia, and numerous bizarre and binucleate normoblasts in the bone marrow. The acidified serum lysis test (Ham's test) performed with 5 normal sera was positive. The patient's red blood cells showed a markedly increased expression of the i red blood cell antigen.- - - - - - - - - - ranking = 1keywords = antigen (Clic here for more details about this article) |
3/10. A case of congenital dyserythropoietic anemia type II associated with hemochromatosis.A 54-year-old woman with anemia, diabetes mellitus and liver dysfunction was admitted to our hospital. Numerous binucleated erythroblasts in the bone marrow, a positive serum acidified test, and the presence of anti I and anti i antigens on the surface of her erythrocytes indicated that she had congenital dyserythropoietic anemia (CDA) Type II. hemochromatosis was confirmed by a liver biopsy. This case is a sibling of a patient with CDA Type II reported by Omine et al in 1981 (Acta Haematol Jpn 44:1). They report that no physical or hematological abnormalities were found when she was examined at the age of 29 years. Twenty-five years later, she developed CDA Type II and hemochromatosis. This case indicates that long-term observation of the family members of a patient with CDA Type II is necessary.- - - - - - - - - - ranking = 1keywords = antigen (Clic here for more details about this article) |
4/10. Congenital dyserythropoietic anemia type I: report of a pair of siblings.Two siblings affected with congenital dyserythropoietic anemia type I are described. They are the sixth familial occurrence reported. Particularly interesting is the comparison between the course and laboratory data of our cases. An unusual finding is the presence of the antigen 'i' on the erythrocytes of both patients.- - - - - - - - - - ranking = 1keywords = antigen (Clic here for more details about this article) |
5/10. Congenital dyserythropoietic anaemia (type II) presenting with haemosiderosis.A 39-year-old female with type II congenital dyserythropoiesis presented with iron overload. The clinical and haematologic features were an anaemia of variable severity, splenomegaly, numerous bizarre and binucleate normoblasts in the bone marrow, with prominent submembranous cisternae in the late forms, a positive Ham's acid lysis test and aberrant expression of the I and i red cell antigens. The iron overload resulted from gross ineffective erythropoiesis, with accelerated plasma iron turnover and increased absorption aggravated by inappropriate replacement therapy for past episodes of anaemia.- - - - - - - - - - ranking = 1keywords = antigen (Clic here for more details about this article) |
6/10. An example of anti-Yta demonstrating a change in its clinical significance.The clinical significance of some red cell alloantibodies remains in doubt and can best be studied with long-term 51Cr survival studies. We report a patient whose IgG anti-Yta was initially shown not to shorten the lifespan of 51Cr-labeled Yt(a ) red cells. At the time of this study, the subclass of the antibody could not be determined. Twelve weeks after transfusion with 4 units of Yt(a ) red cells, the alloantibody for the first time was demonstrable as IgG1; a repeat radiolabeled red cell survival demonstrated significant shortening of the lifespan of Yt(a ) red cells when they were followed for 7 days. These cells had a marked 'two-component' survival curve. Because the patient also demonstrated autoantibody coating his red cells, the clinical effect of this autoantibody was followed with autologous red cells labeled with 111In; the survival of autologous red cells was normal throughout these studies. Evaluation of the clinical significance of an alloantibody in a patient may require long-term 51Cr red cell survival studies and repetition of these studies after exposure to large quantities of the antigen.- - - - - - - - - - ranking = 1keywords = antigen (Clic here for more details about this article) |
7/10. Aberrant pattern of red cell membrane and cytosolic proteins in a case of congenital dyserythropoietic anaemia.We report an unusual case of congenital dyserythropoietic anaemia (CDA). The propositus is a 25-year-old gipsy female presenting with a recessively inherited haemolytic anaemia. The diagnosis of CDA was based on erythrokinetic data and the morphological appearance of the erythroid precursors. The direct assay of HEMPAS antigen was negative. In peripheral blood there were 15% dacryocytes. The red cell membrane protein pattern was dramatically altered, with four major aberrant bands. Band a (mol wt 86,000) was at the lower edge of band 3, band b (mol wt 82,000) was below band 3, band c (68,000) and band d (67,000) were below band 4.2. In addition, there was an array of aberrant minor bands below band d. Gel densitometric determinations and immunological characterization showed that these bands did not derive from any of the major components of the membrane. In fact, membrane proteins appeared normal in many respects, although periodic acid-Schiff staining revealed an apparent decrease of sialoglycoproteins. The major aberrant bands a, b and c occur in very low amounts in controls. These bands, as well as band d, also exist in normal cytosol and were strongly increased in the propositus.- - - - - - - - - - ranking = 1keywords = antigen (Clic here for more details about this article) |
8/10. Human red cell Aquaporin CHIP. II. Expression during normal fetal development and in a novel form of congenital dyserythropoietic anemia.Channel-forming integral protein (CHIP) is the archetypal member of the Aquaporin family of water channels. Delayed CHIP expression was shown recently in perinatal rat (Smith, B. L., R. Baumgarten, S. Nielsen, D. Raben, M. L. Zeidel, and P. Agre. 1993. J. Clin. Invest. 92:2035-2041); here we delineate the human patterns. Compared with adult, second and third trimester human fetal red cells had lower CHIP/spectrin ratios (0.72 /- 0.12, 0.94 /- 0.22 vs 1.18 /- 0.11) and reduced osmotic water permeability (0.029, 0.026 vs 0.037 cm/s); CHIP was already present in human renal tubules by the second trimester. A patient with a novel form of congenital dyserythropoietic anemia (CDA) with persistent embryonic and fetal globins and absent red cell CD44 protein was studied because of reduced CHIP-associated Colton antigens. Novel CDA red cells contained < 10% of the normal level of CHIP and had remarkably low osmotic water permeability (< 0.01 cm/s), but no mutation was identified in Aquaporin-1, the gene encoding CHIP. These studies demonstrate: (a) unlike rat, human CHIP expression occurs early in fetal development; (b) red cell water channels are greatly reduced in a rare phenotype; and (c) disrupted expression of red cell CHIP and CD44 suggests an approach to the molecular defect in a novel form of CDA.- - - - - - - - - - ranking = 1keywords = antigen (Clic here for more details about this article) |
9/10. Observations on two members of the Swedish family with congenital dyserythropoietic anaemia, type III.Two affected individuals of the Swedish family with CDA, type III, in which the disease is transmitted as an autosomal dominant character, were studied. Both cases displayed features hitherto undescribed in this family but described in patients with CDA, type III, in whom the inheritance may have been as an autosomal recessive character. Such features were: (a) haemosiderinuria, (b) grossly disorganised erythroblast nuclei, (c) differences in the ultrastructural appearances of individual nuclei within the same multinucleate erythroblast and (d) intraerythroblastic inclusions resembling precipitated globin chains. In both cases the giant mononucleate erythroblasts and the multinucleate erythroblasts had total dna contents up to 28c (1c = haploid dna content) and 48c respectively, and some dna synthesising bi- and multinucleate erythroblasts contained one or more nuclei which were unlabelled with 3H-thymidine. These findings are similar to those in patients with the autosomal recessive type of disease. Thus no major phenotypic differences are yet apparent between cases of CDA, type III, with different patterns of inheritance. Analysis of the surface erythrocyte proteins of the 2 Swedish CDA, type III, patients with monoclonal antibodies recognising Band 3, glycophorins A, B, C and D, Rh, CD44, CD47, CD55, CD58, CD59, Lutheran, Kell, LW and acetylcholinesterase did not reveal any gross abnormality of expression of these proteins. A slightly altered expression of blood group antigens A and H was revealed by the lectins dolichos biflorus and ulex europaeus and the Mr of Band 3 as judged by SDS polyacrylamide gel electrophoresis was also slightly reduced, suggesting that there may be minor alterations in the degree of N-glycosylation of some red cell membrane constituents.- - - - - - - - - - ranking = 1keywords = antigen (Clic here for more details about this article) |
10/10. Composition of the intra-erythroblastic precipitates in thalassaemia and congenital dyserythropoietic anaemia (CDA): identification of a new type of CDA with intra-erythroblastic precipitates not reacting with monoclonal antibodies to alpha- and beta-globin chains.Ultrathin sections of bone marrow cells from two patients with homozygous beta-thalassaemia, two patients with haemoglobin H (HbH) disease, a patient with congenital dyserythropoietic anaemia (CDA) type III and two patients with severe congenital dyserythropoietic anaemia of an unusual type were reacted with mouse monoclonal antibodies against various globin chains and the reaction visualized using a gold-labelled goat antibody against mouse IgG. The multiple rounded intra-erythroblastic inclusions found in homozygous beta-thalassaemia reacted with the monoclonal antibody against alpha-globin chains but not beta-globin chains, thus confirming that they consisted of precipitated alpha-globin chains. The branching intra-erythroblastic inclusions found in HbH disease and CDA type III reacted with the monoclonal antibody against beta-globin chains but not alpha-globin chains, indicating that they consisted of precipitated beta-globin chains. The two patients with severe CDA had been transfusion-dependent since infancy, had a normal alpha:beta globin chain synthesis ratio or parents with normal red cell indices, displayed prominent dysplastic changes in their erythroblasts, and had intra-erythroblastic inclusions resembling those seen in homozygous beta-thalassaemia. However, unlike those in beta-thalassaemia, the inclusions in these two patients did not react with the monoclonal antibody against either alpha- or beta-globin chains. The inclusions reacted with antibody against zeta-globin chains, but detailed studies in one of the patients indicated that the antigen involved was not zeta-globin. These patients have features not reported in the condition known as dominantly inherited inclusion body beta-thalassaemia and appear to suffer from a novel type of CDA in which the intra-erythroblastic inclusions may consist of some non-globin protein or structurally-abnormal alpha-globin chains.- - - - - - - - - - ranking = 1keywords = antigen (Clic here for more details about this article) |
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