Polyagglutination: a rare mechanism for intravascular hemolysis.
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Biomedical subjects
Publications and source records attributed to C Levene.
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The lectin purified from Erythrina corallodendron seeds which binds N-acetyllactosamine greater than N-acetyl-D-galactosamine greater than alpha and beta galactosides greater than D-galactose was examined for its ABO(H) blood group specificity. It has been shown that this lectin causes the strongest hemagglutination of O(H) and weakest of Oh(Bombay) red blood cells, and interacts with the H antigen in association with the I antigen. The reactions of Erythrina corallodendron and Erythrina indica lectins (which are similar in sugar specificity) with erythrocytes of different ABO(H) and Ii blood groups (the I bloods were all from adults and the i from either cord or adult bloods) revealed the following order of activity: O(H)I greater than A2 I greater than O(H)i adult greater than A2BI greater than BI greater than O(H)i cord greater than A1I greater than A1i adult greater than Bi cord greater than A1BI greater than Ai cord greater than ABi cord greater than OhI. The Erythrina indica lectin showed a lower differentiation between the agglutination of O(H) and Oh erythrocytes. Both Erythrina lectins exhibited H/HI blood group preference but were not inhibited by the saliva from ABO(H) "secretors". Thus they may be classified with the Cytisus sessilifolius, Lotus tetragonolobus and Laburnum alpinum lectins which are inhibited by lactose but not by H blood group substances in secretions.
The Dra antigen belongs to the Cromer-related blood group system, a series of antigens on decay accelerating factor (DAF), a glycosyl-phosphatidylinositol-anchored membrane protein that protects host cells from complement-mediated damage. We studied the rare inherited Dr(a-) phenotype to ascertain the associated biochemical and functional changes in DAF and to characterize the basis for this polymorphism. Radioimmunoassay assay and flow cytometric analysis of Dr(a-) erythrocytes demonstrated 40% of normal surface expression of DAF but normal levels of several other glycosyl-phosphatidylinositol-anchored proteins, distinguishing this phenotype from that of paroxysmal nocturnal hemoglobinuria. Western blots confirmed this reduced DAF expression and indicated a slightly faster mobility of the molecule on SDS-PAGE. Despite the reduced DAF expression, Dr(a-) erythrocytes functioned normally in the complement lysis sensitivity assay. Utilization of the polymerase chain reaction to amplify mononuclear cell genomic DNA from three unrelated Dr(a-) individuals demonstrated that a point mutation underlies the Dr(a-) phenotype: a C to T change in nucleotide 649 resulting in a serine165 to leucine change. This defines the Drb allele of DAF, which can be distinguished from Dra by a Taq I restriction fragment length polymorphism. We created transfected Chinese hamster ovary cell lines expressing either the Dra or the Drb allelic form of DAF. These allele-specific transfectants were tested by inhibition of hemagglutination or flow cytometry and confirmed the specificity of anti-Dra alloantisera. The allele-specific transfectants could form the basis of a new serological approach to immunohematology.
Polyagglutination is a rare disorder which has been associated with intravascular hemolysis (Levene et al.: Transfus Med Rev 2:176-185, 1988). In this condition cryptantigens exposed on the red blood cell membrane agglutinate with compatible sera and with lectins. A 76 year-old man with an acute abdomen due to a perforated tumor of the colon and severe fatal intravascular hemolysis is described. Th polyagglutination of the red blood cells was found.
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Haemophilus influenzae type b expressing fimbriae showed no adherence to buccal epithelial cells and no agglutination of erythrocytes from three AnWj-negative siblings in one family. Hemagglutination of erythrocytes from 13 AnWj-positive members of the same family and from 24 controls was normal, and H. influenzae adhered well to buccal epithelial cells from them. These data indicate that the expression of epithelial and erythrocyte receptors for H. influenzae is inherited concomitantly. Combined with previous data (L. van Alphen, J. Poole, L. Geelen, and H. Zanen, Infect. Immun. 55:2355-2358, 1987), the results show that the receptor molecules on the surfaces of the epithelial cell and the erythrocyte are different but that the binding sites for the fimbriae of H. influenzae are similar.
Anti-Gerbich type anti-Ge3 antibodies were identified in the serum of a woman of mixed ethnic origin from Cape Town. The woman had type Ge:-2,-3 (Gerbich) red cells on which there was no evidence of weakened Kell antigens. Her red cells were also Dantu-positive.
Th polyagglutinability is characterized by the agglutination of the red blood cells (RBC) by Arachis hypogaea, Medicago disciformis, Vicia cretica but, in contrast to the T phenomenon, not by Glycine max (Glycine soja). Because Th transformation of RBC has been obtained in vitro, the mechanism of Th polyagglutinability expression has been studied and reproduced experimentally. An enzyme with neuraminidase specificity has been isolated from the culture supernatant of Corynebacterium aquaticum, and further characterized (MW = 55,600 kDa, pH = 5.5, Km = 0.138 microM, Kcat = 0.22 micrograms). Reversely, Th transformation of RBC could be obtained by using other neuraminidases but in very mild conditions of hydrolysis. From our results, it can be concluded that by the release of less than 20 micrograms of sialic acid per 10(10) RBC, Th reactivity can be induced whereas hydrolysis of greater amounts of sialic acid (greater than 20 micrograms/10(10) RBC) give the classical T polyagglutinability.
One hundred thirty-two patients with breast cancer were examined for exposure of cryptantigens on their erythrocytes (RBC) using a lectin panel consisting of Arachis hypogaea and Glycine soja. Eight had exposed cryptantigens; of the eight, five were classified with additional lectins as T-polyagglutination type and three as Th-polyagglutination. A control group of 300 healthy blood donors had no exposed cryptantigens on their RBC. These findings could not be correlated with the staging of the tumor, extension of metastases, or positive estrogen or progesterone receptors of malignant tumor cells. Only one study has been found that describes the incidence of agglutination of erythrocytes from cancer patients using a monoclonal antibody, which detected an epitope on the RBC from cancer patients and was considered to be distinct from the antigen bound by naturally occurring anti-T. Studies have been made describing polyagglutinable sites on breast cancer tumor cells, where there was a much higher incidence. This discrepancy can be explained either by a difference in the methods used to search for cryptantigen exposure on the various types of cells, or by the existence of a different mechanism, which causes the exposure of cryptantigens on RBC as opposed to malignant breast tumor cells.
We report the presence of sickle cell trait in several members of a white Jewish family. The trait was discovered when the propositus developed massive splenic infarction at high altitude. No erythrocyte markers characteristic of African ancestry were detected in any of the family members. This is the first bona fide documentation of sickle trait among white Jews.
Extracts of the green marine alga Ulva lactuca collected along the seashore of Tel-Aviv exhibit hemagglutinating activity towards papain-treated human erythrocytes. This hemagglutinating activity was shown to be inhibited by L-fucose and EDTA, and to be relatively resistant to heating at 60 degrees C, while sensitive to low pH. Like the lectin of Ulex europeus, the Ulva lectin exhibits blood group H specificity. It agglutinates most strongly erythrocytes of blood group 0(H) followed by B greater than A greater than AB. A2 and A2B erythrocytes are agglutinated by it considerably more strongly than A1 and A1B respectively. Bombay 0(hh) type erythrocytes are almost non-reactive. The lectin can be stored at -20 degrees C for years.
Three examples of an antibody were found to be detecting a red cell polymorphism probably identical to MER2. The antibodies were made by Jews originating from India and living in Israel. Two of them were sibs and the third was unrelated. All 3 had kidney disease requiring renal dialysis and regular blood transfusion. In 2 cases the antibodies were detected before dialysis was started and before the patients had been transfused. The human antibodies reacted with red cells of 90% of Israeli blood donors tested. In tests on selected blood donors, 82 English and 56 Israeli, one of the human antibodies gave almost identical reactions to those given by monoclonal anti-MER2. Anomalous reactions were probably due to anti-Bga. Two of the human antibodies completely blocked, and one partially blocked, the reaction of monoclonal anti-MER2 with MER2+ red cells.
A case of angiomyolipoma with cryptantigen exposure on the red blood cells is described. The exposed cryptanigen was classified with lectins as T-polyagglutination. This is the first case described of T-cryptantigen exposure associated with angiomyolipoma.
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A hospital population at high risk for red cell polyagglutination was studied prospectively in search for cryptantigen exposure. The patients included in this study suffered from: malignancies, sepsis, direct antiglobulin test (DAT) negative anemias and various combinations of these three. 238 patients were examined, and 18 of these (7.6%) were found to have exposed cryptantigens on their erythrocytes. This is an unexpectedly high percentage. Our findings suggest that cryptantigen exposure on the red cells is a more common phenomenon than previously described, especially when looked for in a carefully chosen population. The red cells of these patients are potentially polyagglutinable, and screening with lectins will ensure their pretransfusion identification and evaluation.
Women with the rare blood group p are known to have an increased rate of abortions. The case of a 36-year-old woman is presented who had had 7 spontaneous abortions in the first trimester and no live child. When treated by plasma exchange begun early in pregnancy and continued until the 29th week, she delivered a normal child. Time to begin, amount and length of time necessary to continue plasma exchange in these patients are considered. In addition, the question of which fraction of the anti-PP1Pk could be responsible for abortion is discussed. To our knowledge, this is the first case of a woman of p phenotype with no live children but with multiple abortions treated by this method, which should be seriously considered in similar cases.
A case of acute haemolytic anaemia is described in a child. Tx polyagglutination of his red cells was observed, but no direct association with the anaemia could be proved. Polyagglutination was suspected because of irregularities in the AB0 blood grouping. Confirmation of the cryptantigen Tx was made when the patient's red cells were tested with lectins including Arachis hypogaea, Glycine soja, and Vicia cretica. Examination of family members showed Tx polyagglutination on the red cells of 2 siblings. The Tx polyagglutination was a transient phenomenon lasting 4-5.5 months, and could have been caused as the result of some unidentified bacterial or viral infection. Guidelines for transfusion therapy are suggested in patients in whom polyagglutination is recognised.