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W W Socha

Publications and source records attributed to W W Socha.

At least 37 records · Page 2Linked to original sources

Diversity of human anti-D monoclonal antibodies revealed by reactions with chimpanzee red blood cells.

Fifty-three human anti-D monoclonal antibodies (mAbs) revealed a striking diversity of reactions in tests with panels of chimpanzee red blood cells (RBCs) of various R-C-E-F blood group phenotypes (counterparts of the human Rh-Hr groups). The reactivities of these antibodies, which depended on the agglutination technique used, could be classified into four main types. These patterns of reactivity of anti-D mAbs with chimpanzee RBCs showed only limited correlation with types of reactions observed with human D variant RBCs. Primate red cells may, therefore, constitute an independent test system for subclassification of human monoclonal antibodies. Comparison of reactivities of human anti-D mAbs with chimpanzee and human D variant RBCs confirms the homology between the chimpanzee Rc, and the human D antigens. The chimpanzee Rc shares with human D the epitopes epD5, epD6/7 and epD8, but lacks epitopes epD1, epD2, epD3 and epD4 of the Rh mosaic, thus resembling the human D variants IVb and Vc.

Animals↗

Survival of human monoclonal anti-Rho (D) antibodies in the rhesus monkey.

In vivo half-life of a 125I-labeled human anti-D monoclonal antibody (mAb) and that of 131I-labeled Rho-GAM was assessed in a rhesus monkey injected simultaneously with both reagents. The half-life of the mAb was 7.9 days, compared to 17 days of Rho-GAM. Survival of the second dose of mAb, given 34 days after the first injection, was identical to that of the first dose, thus showing that the human mAb did not elicit an immune response. The in vitro produced human mAbs appear to be an alternative, unlimited source of anti-D antibodies for possible use in prevention of feto-maternal Rh immunization.

Animals↗

Anti-human red cell monoclonal antibodies produced by macaque-mouse heterohybridomas.

Eight monoclonal antibodies (Mabs) against human red cells were produced by macaque-mouse heterohybridomas. All Mabs uniformly reacted with all human red blood cells tested, but only some agglutinated the red cells of anthropoid apes occasionally detecting intraspecies polymorphisms. None was reactive with blood of Old and New World monkeys. One of the Mabs recognized the Vc antigen of the chimpanzee V-A-B-D system, the homologue of the human M-N blood group system.

Animals↗

Polymorphisms and gross structure of glycophorin genes in common chimpanzees.

Using human alpha glycophorin cDNA probe and six restriction enzymes, we examined the homologues of human glycophorin genes in genomic DNA of 11 unrelated chimpanzees. We show that, in contrast to the human, the chimpanzee exhibits an unusual array of nonrandomly distributed restriction fragment length polymorphisms (RFLP). No clear correlation was found between the RFLP and the V-A-B-D blood-group phenotypes of the subjects, with one possible exception. However, pairs of allelic RFLP occurring at a relatively high frequency were identified. In addition, the homology of chimpanzee glycophorin genes to the human genes was examined using as probes synthetic oligonucleotides specifying distinct regions of human glycophorin genes. We show that the glycophorin gene family in the chimpanzee consists of at least three members that are homologous to the human alpha, delta, and E genes (glycophorins A, B, and E) and may share a similar gross structure and overall organization.

Alleles↗

Monoclonal antibodies directed against human Rh antigens in tests with the red cells of nonhuman primates.

Monoclonal antibodies against Rh related antigens on human red cells often crossreact with the red cells of the highest subhuman primate species. Depending on specificity of antibody, the species tested, and technique used, these reactions can be either species-specific or type specific. In tests with chimpanzee red cells, some of the latter type reactions have specificities related to the R antigen of the R-C-E-F blood group system of chimpanzee; specificities of some others seem to be unrelated to any known chimpanzee blood groups. Monoclonal anti-D reagents that give uniformly positive reactions with human D-positive (common and rare types) red cells, display wide individual differences in tests with chimpanzee blood. This indicates that there are minute structural variations of antibody molecules from one monoclonal anti-D antibodies apparently have no bearing on recognition of the D combining site on the human red cells, but come into play when in contact with chimpanzee rbcs. Some of the monoclonal antibodies directed against Rh and LW molecules are distinguished by unusually strong reactions with the red cells of the Old World monkeys (macaques and baboons), which is in contrast with negative or weak reactions of the same antibodies with the red cells of anthropoid apes and human bloods. One may recall, that polyclonal anti-Rh sera do not react with the blood of rhesus monkeys, the phenomenon that was the source of controversy surrounding the discovery of the rhesus factor of the human blood.

Animals↗

Complexity of the Rh antigen demonstrated by comparative tests using antisera of human and primate origins.

Comparative analysis of two antisera, one produced in chimpanzee and another of human origin, demonstrates the existence of the whole spectrum of antibodies directed against at least four, and possibly five, antigenic determinants connected with the Rh reactivity. Some of the determinants are shared by chimpanzee and human red cells, while others are restricted to one species only. Based on this study, it is suggested that both the human Rh(D)-positive type and its chimpanzee counterpart, the Rc-positive type, could be of common origin, while the negative types are the results of later, parallel events during the evolution.

Animals↗

Polymorphism of glycophorins in nonhuman primate erythrocytes.

Using immunoblotting techniques and polyclonal antisera to human erythrocyte alpha glycophorin, we show that erythrocytes of several species of nonhuman primates, including representatives of anthropoid apes (19 chimpanzees, 3 gorillas, 6 orangutans, and 3 gibbons) and Old World monkeys (3 baboons, 5 rhesus monkeys, and 6 cynomolgus macaques), contain human alpha glycophorin-like molecules. Each species displays a unique glycophorin profile; in anthropoid apes the profile is more complex than in Old World monkeys and more similar to that seen in humans. The chimpanzee was the only species in which human delta-like glycophorin was detected but it differed from its human counterpart in electrophoretic mobility and reaction with M-specific monoclonal antibody. In contrast to humans, highly polymorphic glycophorin profiles were observed in each species of anthropoid apes and three distinct patterns were defined in each. No such polymorphism has been found so far among the Old World monkeys in the limited number of animals studied. The major glycophorins in all species but the chimpanzees failed to react with M- or N-specific monoclonal antibodies, suggesting structural differences from the human within the amino terminal regions. The reaction with the minor glycophorins showed inter- and intraspecies variability. All glycophorins, except delta-like glycophorin in the chimpanzee, reacted with the antiserum to the carboxyl terminal fragment of human alpha glycophorin, indicating a structural relation to the human in this region. An unexpected correlation was observed, in the chimpanzee, between the patterns of electrophoretically resolved glycophorins and the V-A-B-D blood-group phenotypes, allowing the assignment of each determinant to specific glycophorin bands. The basis for the differences observed between human and nonhuman primate glycophorins is not clear but the possibilities include a common nonpolymorphic ancestor and differences in selective pressures.

Animals↗

The chimpanzee M blood-group antigen is a variant of the human M-N glycoproteins.

Chimpanzee erythrocytes express strong M but weak, occasional N blood-group activity, as detected by anti-M and anti-N reagents. We have found that the M activity is carried by a major membrane glycoprotein that is similar but not identical to the human MM glycoprotein (glycophorin A). We have isolated and characterized this glycoprotein from erythrocyte membranes of four individual chimpanzees. The purified glycoproteins strongly inhibited agglutination of M cells by rabbit anti-human M sera and only weakly inhibited the agglutination of N cells by rabbit anti-human N sera. They also displayed medium-to-strong inhibitory activity against chimpanzee iso- and crossimmune antisera tested with chimpanzee erythrocytes of various V-A-B-D and Wc specificities, which are known as chimpanzee extensions of the human type M-N system and the Miltenberger counterpart, respectively. Each glycoprotein was cleaved with CNBr into three fragments, whose size, solubility, and composition were analogous to those obtained by similar treatment of the human M-N antigens. The amino-terminal fragment was found to be a glycooctapeptide whose amino acid composition and partial sequence indicated that it is an intermediate form of the human M and N glycooctapeptides. Its carbohydrate content comprised two threonine-linked saccharide units that, although similar in composition to the human threonine-linked units, were fewer in number than the three units found in the corresponding human glycooctapeptides. Structural similarities to the human antigens strongly suggest that the amino terminus bears the major antigenic determinants of the molecule, and the occurrence in this region of numerous, albeit rare, variants among humans and in chimpanzees indicates that the corresponding coding sequence of the structural gene is particularly susceptible to mutational events. We conclude that the chimpanzee M gene product is a variant of the human type and that the chimpanzee gene is an allele of the human polymorphic M-N locus.

Amino Acid Sequence↗

The BP graded blood group system of the baboon: its relationship with macaque red cell antigens.

The first blood group system to be defined in baboons by means of isoimmune agglutinating reagents is composed of five graded types: B4, B3, B2, B1 and b, inherited, as postulated, by five allelic genes with decreasing dominance order. There are significant differences in distribution of the BP blood groups between hamadryas baboons on the one hand, and cynocephalus and anubis on the other, which may serve as auxiliary taxonomic criteria. Antibodies of specificities related to the BP graded antigens are found in the sera of presumably nonimmunized baboons, and also in the rhesus isoimmune antisera that detect one of the subtypes of the so-called Drh graded system of macaques. These findings point to ubiquity of the BP or BP-like antigens, and to the close serological relationship between BP baboon and Drh macaque red cell antigens, perhaps as evidence of a common ancestral antigen which gave rise to a diverging set of graded subspecificities of baboon and macaque red cells, respectively.

Animals↗

Perfluorocarbon enhancement of heterologous red cell survival: a reticuloendothelial block effect?

The intravascular survival of human erythrocytes transfused to primate animals was prolonged by infusing the recipients with a perfluorocarbon red cell substitute (Fluosol DA). This effect is probably due to transient block of the animals' reticuloendothelial system by the perfluorocarbon emulsion. Perfluorocarbon compounds could be used to study the role of reticuloendothelial function in the immune destruction of red cells.

Animals↗

Human sickle erythrocytes: survival in chimpanzees.

The survival characteristics of human sickle (SS) erythrocytes (RBCs) transfused to intact chimpanzees were determined. The mean post-transfusion recovery of 51Cr-labelled SS RBCs in four chimpanzees was 30.5% +/- 15.2 SD, and the half-life survival was 4.2 h +/- 0.8 SD. The recovery of control (hemoglobin AA) human red cells in five chimpanzees was complete and their mean intravascular T 1/2 was 22.3 h. Shorter survival of sickle erythrocytes was also shown by transfusing chimpanzees with mixtures of human cells such as 51Cr AA RBCs and 59Fe SS RBCs, or 51Cr SS RBCs and non-labelled fetal (cord blood) erythrocytes. The difference in survival of AA and SS RBCs resembles that in human recipients and was probably caused by sickling of SS cells in the chimpanzee circulation. These primate animals could, therefore, be used as a model for in vivo studies of sickle cell disease.

Anemia, Sickle Cell↗

Transfusion of incompatible blood in rhesus monkeys and baboons.

Four pairs of rhesus monkeys and five pairs of baboons were cross-transfused with large volumes of blood given at intervals varying from 3 weeks to 30 months. Although no acute transfusion reactions were observed, there was a significant reduction in survival rate of the transfused erythrocytes correlated with the level of antibodies in recipient's serum. The immune response of the recipient animal depended on the interval between transfusions and, to some extent, on the number and kind of erythrocyte incompatibilities between the recipient and the donor. These results emphasize the importance of blood group and compatibility testing prior to transfusion.

ABO Blood-Group System↗

Blood groups of Barbary apes (Macaca sylvanus).

32 Barbary macaques were all found to be secretors of the A and H blood group substances and to have an M-like agglutinogen on their red cells. Hemagglutination tests for other human-type red cell specificities were negative. In contrast, several so-called simian-type specificities were detected on the erythrocytes of Barbary apes by means of the cross-reacting rhesus and baboon antisera. Among these, only the specificities of the graded Drh blood group system were found to be polymorphic in this species of macaques. Blood groups of Barbary apes are compared with those of several other species of macaques and some taxonomic aspects of blood grouping tests are discussed.

Animals↗

Survival of human erythrocytes in primate animals.

The recovery and survival of small quantities of 51Cr-labelled human erythrocytes (RBCs) transfused to nonhuman primates were measured. In two chimpanzees all of the human RBCs circulated 15 min after transfusion and were subsequently removed from the animals' blood with a half-life (T1/2) of 1.6 and 2.4 days. In baboons and rhesus monkeys over 95% of the human RBCs were cleared within 15 min after injection. Animal species, rather than antibody characteristics or titer, was an important determinant of the human RBC survival. Transfusion of human RBCs to chimpanzees can thus be explored as a test system to study human erythrocyte disorders.

Animals↗