Tissular expression of ABH and Lewis antigens in humans and animals: expected value of different animal models in the study of ABO-incompatible organ transplants.
Explore the source record for details and available documents.
Biomedical subjects
Publications and source records attributed to R Oriol.
Explore the source record for details and available documents.
Patients with hydatid cysts and controls of the same Tunisian area were typed for ABO, Lewis and secretor phenotypes. A high incidence of red cell Le(a-b-) phenotype (34-37%) was found among hydatid cyst patients as compared to normal controls (13-16%). However, a large proportion of the patients with Le(a-b-) red cell phenotype had discordant red cell and saliva Lewis phenotypes since they secreted Lea and/or Leb antigens in saliva. In addition, 1 patient with Le(a+b-) red cell phenotype secreted Leb antigen in saliva. The remaining patients and all the controls had concordant red cell and saliva Lewis phenotypes. The discordant results between the phenotypes obtained in serum and saliva of hydatid cyst patients are probably the consequence of a decrease in the concentration of the circulating Lewis glycosphingolipids, secondary to the disease.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
A monoclonal antibody YPC 44.3 which reacts with human large intestinal goblet cell mucus has been used to examine normal gastrointestinal mucosa and a series of gastric and colorectal carcinomas in an immunohistochemical study. In normal colonic mucosa the antibody is shown to detect an antigen which is expressed polymorphically and depends on the presence of the active allele at the Lewis locus for its expression. However the antigen appears distinct from regular Lewis antigens on the basis of immunoabsorption studies and organ distribution. Results of immunostaining tumours show no correlation with the site, classification or grade of tumour or the type of metaplasia adjacent to gastric cancers. The relationship of YPC 44.3 to other mucus antibodies and the importance of screening tissues with a wide range of blood group phenotypes is discussed.
ABH antigens have been demonstrated in the posterior root ganglia (PRG) of 3 primate species (marmoset, baboon and man). Their expression corresponded to the ABO phenotype of the individual and was independent of the secretor gene. In marmosets more cells were positive for H (33 +/- 9%) than for A (19 +/- 6%). In baboons A or B antigens were more easily detected (66 +/- 9%) than the H antigens (48 +/- 5%). In humans more than two-thirds of PRG cells were positive for H but only a small proportion of these were positive for A or B. The ABH antigens were found mainly in the small and intermediate-size neurons whose central processes project to lamina II of the spinal cord posterior horn. Unipolar neurons of the Gasserian ganglion, neurons of the mesencephalic nucleus of the trigeminal nerve and of some visceral ganglia have also been shown to express these antigens which are also present in the fibre layer and glomeruli of the olfactory bulbs.
The present knowledge on chemical, enzymatic, serologic and genetic aspects of ABH antigens is reviewed in an effort to produce a simple and coherent genetic model for the biosynthesis of these antigens and chemically related structures. The genetic control of type 1 (Le(a), Le(b), Le(c) and Le(d)), type 2 (X, Y, I, and H), type 3 and type 4 ABH and related antigens in different animal and human tissues is analyzed, taking into account the properties of the glycosyltransferases which are involved in their synthesis and considering possible competition for common acceptor and donor substrates. The phylogeny of ABH determinants shows that they appeared as tissular antigens much earlier than as red cell antigens. The ontogeny of ABH antigens suggests that they behave as differentiation antigens, and an effort is made to correlate their tissular distribution in the adult with the embryological origin of each tissue.
Anti-H antibodies from 2 homogeneous subgroups of H-deficient individuals (Bombay and Réunion phenotypes) were studied for their specificity with regard to synthetic H oligosaccharides. It appears that Bombay individuals synthesize large amounts of both anti-H type 2 and anti-H type 1 antibodies, whereas Réunion individuals may possess strong anti-H type 1 antibodies, but have only weak anti-H type 2 antibodies in their serum. This can be explained by the presence of small amounts of H-type 2 determinants on the erythrocytes of Réunion individuals contrasting with the complete lack of H determinants on the red cells of Bombay individuals.
Human as well as animal anti-Lewis reagents were shown to have different binding patterns to synthetic structures chemically related to the Lewis epitopes. Two main types of cross-reactions were found: (1) Cross-reactions among type 1 Lewis epitopes (Lea, Leb and Lewis disaccharide). This type of cross-reaction among different type 1 structures was predominant in anti-Lea reagents (16 out of 18), although it was also present in some anti-Leb reagents (4 out of 14). (2) Cross-reactions of Lea and Leb with their type 2 isomers X and Y. The Leb-Y cross-reaction was more frequent (7 out of 14) than the Lea-X cross-reaction (2 out of 18). The serological property of some anti-Lewis reagents reacting with cord cells ('Lex') is also shown to be heterogeneous although probably related to common features of the type 1 Lea and Leb epitopes and independent of the type 2 X and Y epitopes.
Explore the source record for details and available documents.
In the rat olfactory apparatus and inner ear the H antigen was first detected at the 15th day of gestational age. The B antigen appeared at the 16th day. In the olfactory apparatus H and B antigens were first detected in cells of the olfactory mucosa and of the olfactory bulb primordium. Towards the 16th and 17th days many small positive cells were seen between these two areas. In newborn and adult rats, olfactory bulb H and B antigens were restricted to the processes of the peripheral primary sensory cells. Both H and B antigens were detected in the epithelium of the inner ear and were later concentrated in the hair cells of the organ of Corti, the utricle and the saccule.
Lymphocytotoxic antibodies to the red cell blood groups A and B were purified from human sera by elution from synthetic immunoadsorbents (Synsorbs from Chembiomed). The lymphocytotoxic activity of the eluted antibodies was better preserved when elution was carried out at pH 11, whereas it was less stable when elution was performed at pH3. In addition, complete removal of anti-red cell blood group activity from an anti-HLA serum was easily obtained by adsorption on the corresponding Synsorb without loss of anti-HLA activity.
The sera of H-normal, H-weak and H-deficient individuals transferred the same amounts of ABH and Lewis antigens to lymphocytes in culture, confirming that the circulating ABH and Lewis antigens detected by lymphocytotoxicity are independent of the H-h system. These antigens were, as expected, under the control of the secretor and Lewis systems in the same way as exocrine secretions. These results suggest that both circulating ABH and Lewis glycosphingolipids and exocrine ABH and Lewis glycoproteins can be synthesized by the same tissues.
Explore the source record for details and available documents.
Type 1 antigens (Lea and Leb) of the pyloric mucosa are restricted to the mucus cells of the surface epithelium and the neck. In the duodenum they are present in absorptive and goblet cells of duodenal villi as well as in the glands of Lieberkühn. Type 2 antigens (X, Y, and H) are also present in these areas of the mucosa, and both type 1 and type 2 antigens, in this superficial location, are under the control of the secretor gene. In addition, type 2 antigens are also present in the mucus cells of pyloric and Brunner's glands, but in this deep location they are not controlled by the secretor gene. These results suggest the existence of two differentiation patterns for the expression of glycosyltransferases in the stem cells. The upward differentiation process would favor the expression of the alpha-2-L-fucosyltransferase coded by the Se gene, and the downward differentiation process would favor the expression of the alpha-2-L-fucosyltransferase coded by the H gene. The knowledge of the distribution and the genetic control of type 1 and type 2 antigenic determinants in normal gastrointestinal tract may help to interpret the modifications in the expression of these antigens in pathologic conditions such as neoplasia.
Explore the source record for details and available documents.
Three patients with renal involvement, plasma cell dyscrasia and systemic light chain deposition are reported in whom well characterized amyloid deposits were also found in the vessel walls. This association, not yet reported, is probably more frequent than believed and still brings nearer these two manifestations of monoclonal light chain deposition. Whether or not the finding of amyloid deposits during systemic light chain deposition is a separate entity and modifies the prognosis remains to be answered.
Sera from H normal, secretors and nonsecretors (H/-, Se/- and H/-, se/se), as well as from H-deficient secretors (h/h, Se/- or Bombay secretors) contain enzyme(s) for the transfer of L-fucose in the alpha-configuration to the 2-position of suitable beta-D-galactopyranosyl units. Sera from H-deficient nonsecretors (h/h, se/se; i.e., Bombay nonsecretors) are devoid of such beta-D-Gal alpha-2-L-fucosyltransferase(s). In order to study these enzymes, a comparison was made of the kinetic properties of the enzymes present in the sera of H-normal nonsecretors (H/-, se/se) with those of H-deficient secretors (h/h, Se/se) with those of H-deficient secretors (h/h, Se/-). These studies revealed a clear difference between the two sources of enzyme: (1) the apparent Km for GDP-fucose was four times lower with the H-normal nonsecretor serum (0.008 mM) than with the H-deficient secretor serum (0.028 mM); (2) acceptors with a type 1 or type 3 chain proved to be better than acceptors with a type 2 chain or than phenyl-beta-D-galactopyranoside for the enzyme present in the serum of H-deficient secretor individuals. Indeed, the synthetic type 2 compound, betaDGal (1-->4)-3-deoxy-beta-DGlcNAc-1-OCH3, which cannot act as an acceptor of beta DGlcNAc alpha-3/4-L-fucosyltransferases, remained unchanged in the serum of an H-deficient secretor but was a good acceptor in the serum of an H-normal nonsecretor, and (3) the alpha-2-L fucosyltransferease activity of the H-deficient secretor serum was more sensitive to heat inactivation than that of the H-normal nonsecretor serum (t1/2 at 46 degrees C were 10 min and 75 min, respectively). These results show that at least two distinct alpha-2-L-fucosyltransferases are present in human serum. It is concluded that the enzymatic activity found in the H-deficient secretor serum (h/h, Se/-) could be the product of the Se gene and the enzymatic activity found in the H-normal nonsecretor serum (H/-, se/se) could be the product of the H gene. This conclusion correlates well with the finding that H and Se genes are closely linked and might have derived by gene duplication in the course of evolution.