| 1. |
- Svensson, Lola, 1948
(författare)
-
Chemical basis of ABO subgroups
- 2011
-
Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Despite the ABO histo-blood group system being the most biologically significant in humans the chemical structures that define its various phenotypes still remain largely unresolved. Like all blood group systems there is a significant range in the amount of antigen present on the red cells of an individual and there exists a range of so-called “weak” phenotypes represented by decreasing expression of A or B antigens. There are a variety of known and speculative mechanisms that may result in these weaksubgroups/ phenotypes. Mechanisms resulting in weak-subgroups can include glycosyltransferase catalytic domain mutations and mutations outside the catalytic domain. Mechanisms resulting in weak-phenotypes can include insufficient glycosyltransferase or precursor, secondary antigen acquisition, disruption in biosynthesis, glycosyltransferase redundancy or degeneracy, antibody sensitivity and specificity, chimera/transplantation/transfusion, infection, physiological changes and finally artificial manipulation. Weak-subgroups/phenotypes are potential windows into the biochemistry of the ABO blood group system, due to the absence of dominating structures, and/or enhancement of trace antigens caused by a loss in normal competition. The aim of this thesis was to gain insights into chemical basis of the ABO system by investigation of the mechanisms behind selected A weak-subgroups and/or A weakphenotypes. A selected number of these were then biologically dissected and immunochemically and structurally investigated in details. Structural analysis of complex carbohydrate compounds is a delicate process where information from one technique is compiled with information from other techniques to finally elucidate a reliable identification of structure. It is the combination of analytical tools that allows for robust interpretation of results that give insights to the biosynthetic and genetic basis for the phenotypes. In this thesis it was shown that the probable explanation between the A1 and the A2, apart from the quantitative aspects, is that the A-type 4 structure seems to be missing in the A2 phenotype. TLC investigations into a range of weak-subgroups revealed a range of interesting anomalies, many of which have yet to be investigated. Investigations on an individual A3 phenotype revealed an absence of branched structures as a potential mechanism for the “mixed field” reaction. Also several new structures including extended p-Fs (para-Forssman) structures were found. Finally the Apae phenotype revealed an unexpectedly discovery that this phenotype is caused by expression of the Forssman (Fs) antigen and not A antigens. This leads to a proposal to establish the 31st blood group system, tentatively named FORS. Although the contribution of glycoproteins and polyglycosylceramide to the expression of weak ABO subgroups still remain uninvestigated the analysis of the glycolipids alone has revealed a variety of significant insights into blood group A subtypes/phenotypes.
|
|
| 2. |
- Svensson, Lola, 1948, et al.
(författare)
-
Forssman expression on human erythrocytes: biochemical and genetic evidence of a new histo-blood group system
- 2013
-
Ingår i: Blood. - : American Society of Hematology. - 0006-4971 .- 1528-0020. ; 121:8, s. 1459-68
-
Tidskriftsartikel (refereegranskat)abstract
- Abstract In analogy with histo-blood group A antigen, Forssman (Fs) antigen terminates with α3-N-acetylgalactosamine and can be utilized by pathogens as a host receptor in many mammals. However, primates including humans lack Fs synthase activity and have naturally-occurring Fs antibodies in plasma. We investigated individuals with the enigmatic ABO subgroup Apae and found them to be homozygous for common O alleles. Their erythrocytes had no A antigens but instead expressed Fs glycolipids. The unexpected Fs antigen was confirmed in structural, serological and flowcytometric studies. The Fs synthase gene, GBGT1, in Apae individuals encoded an arginine to glutamine change at residue 296. Gln296 is present in lower mammals whereas Arg296 was found in six other primates, >250 blood donors and Apae family relatives without the Apae phenotype. Transfection experiments and molecular modelling showed that 296Gln reactivates the human Fs synthase. Uropathogenic E.coli containing prsG-adhesin-encoding plasmids agglutinated Apae but not group O cells, suggesting biological implications. Predictive tests for intravascular hemolysis with crossmatch-incompatible sera indicated complement-mediated destruction of Fspositive erythrocytes. Taken together, we provide the first conclusive description of Fs expression in normal human hematopoietic tissue and the basis of a new histo-blood group system in man, FORS.
|
|
| 3. |
- Svensson, Lola, 1948, et al.
(författare)
-
The structural basis of blood group A-related glycolipids in an A3 red cell phenotype and potential explanation to a serological phenomenon
- 2011
-
Ingår i: Glycobiology. - : Oxford University Press (OUP). - 1460-2423 .- 0959-6658. ; 21:2, s. 162-174
-
Tidskriftsartikel (refereegranskat)abstract
- Glycolipids from the red cells of a rare blood group A subgroup individual, expressing the blood group A(3) phenotype with the classical mixed-field agglutination phenomenon, A(2(539G>A))/O(1) genotype, and an unusual blood group A glycolipid profile, were submitted to a comprehensive biochemical and structural analysis. To determine the nature of blood group A glycolipids in this A(3) phenotype, structural determination was carried out with complementary techniques including proton nuclear magnetic resonance (1D and 2D), mass spectrometry (MS) (nano-electrospray ionization/quadrupole time-of-flight and tandem mass spectrometry) and thin layer chromatography with immunostaining detection. As expected, total blood group A structures were of low abundance, but contrary to expectations extended-A type 2 and A type 3 glycolipids were more dominant than A hexaglycosylceramides based on type 2 chain (A-6-2 glycolipids), which normally is the major A glycolipid. Several para-Forssman (GalNAcbeta3GbO(4)) structures, including extended forms, were identified but surmised not to contribute to the classic mixed-field agglutination of the A(3) phenotype. It is proposed that the low level of A antigen combined with an absence of extended branched glycolipids may be the factor determining the mixed-field agglutination phenomenon in this individual.
|
|
