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Institute of Bioorganic Chemistry, Russian Academy of Sciences, Moscow, Russia
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research activity
  • oligosaccharide synthesis
  • neoglycoconjugates
  • glycoarrays
  • supramolecular chemistry
  • influenza
  • transplantology and blood groups
  • oncology
  • natural antibodies
  • glycotargeting
  • Interaction of natural blood group anti-A and anti-B antibodies of recipient with the corresponding antigens of transplanted material often hinders or makes difficult allotransplantation of organs and tissues because antigens A and B are present not only on erythrocytes but on many other organs. A practically convenient way to overcome this obstacle is affinity removal of the corresponding antibodies. We have developed adsorbents on the base of SepharoseFF™ and synthetic trisaccharides A and B attached to the matrix via flexible hydrophilic polymer. Using the type B adsorbent sorption procedure was performed in 1997 for the group 0 patient to whom B group heart (incompatible by antigen system ABH) had been transplanted. As this patient had own natural anti-B antibodies and additional immune process was started due to transplantation of alien organ, lethal case was possible as the consequence of immune rejection. After 14 sorption procedures both antibodies were removed and immune cells stopped to synthesize them, i.e. so-called accommodation took place. Thanks for timely sorption the patient survived. Now, company Pocard (Moscow) produces commercial affinity A ans B columns for the antibodies removal.
    • Lewis Blood Group System. Lewis serologic reagents frequently give inaccurate phenotyping results. Furthermore these serologic reagents are often used in non-serologic assays such as inhibition and immunohistochemistry. In both scenarios knowledge of the fine-specificity and cross-reactivity of these reagents will improve the quality of results obtained. A range of contemporary and historical workshop and developmental Lewis reagents including mouse monoclonal (MAb), human and goat polyclonal (PAb) reagents were evaluated. All were evaluated against both Lewis kodecytes expressing only single Lea, Leb, ALeb, BLeb, Lex, Ley, ALey or BLey antigens and against the same antigens inkjet printed on a paper-based microplate and analysed by enzyme immunoassay. Nine clinical samples were also evaluated. A kodecyte antigen-dilution sensitivity assay was used to establish the ratio of Leb antigen between group A1/A2 and O RBCs.
    A continuum of cross-reactivity from Lex through to H was observed with MAbs. All PAb and few MAb anti-Lea samples and reagents cross-reacted to some degree with Leb antigen. Some PAb and MAb anti-Leb did not cross-react with Lea. All polyclonal goat anti-Leb reagents showed substantial activity against ALeb and BLeb, while no MAb reagent had this activity. A1 RBCs had less than half the Leb antigen of A2/O RBCs. Thus, substantial cross-reactivity of both MAbs and PAbs with related antigens highlights the risks of using serologic reagents in non-serologic assays or against synthetic antigens. The lack of ALeb activity in anti-Leb MAbs explains their poor performance against blood group A1 Le(a-b+) phenotypes.


    Although the nature of the blood groups A and B has been comprehensively studied for a long time, it is still unclear as to what exactly is the epitope that is recognized by antibodies having AB specificity, i.e. monoclonal and polyclonal antibodies which are capable of interacting equally well with the antigens GalNAcα1-3(Fucα1-2)Gal (A trisaccharide) and Galα1-3(Fucα1-2)Gal (B trisaccharide), but do not react with their common fragment Fucα1-2Gal. We have supposed that besides Fucα1-2Gal, A and B antigens have one more shared epitope. The trisaccharides A and B are practically identical from the conformational point of view, the only difference being situated at position 2 of Galα residue, i.e. trisaccharide A has a NHAc group, whereas trisaccharide B has a hydroxyl group. We have hypothesized that the AB-epitope should be situated in the part of the molecule that is opposite to the NHAc group of GalNAc residue. In order to test this hypothesis we have synthesized a polymeric conjugate in such a way that de-N-acetylated A-trisaccharide is attached to a polymer via the nitrogen in position C-2 of the galactosamine residue. In this conjugate the supposed AB-epitope should be maximally accessible for antibodies from the solution, whereas the discrimination site of antigens A and B by the antibodies should be maximally hidden due to the close proximity of the polymer. Interaction with several anti-AB monoclonal antibodies revealed that a part of them really interacted with the synthetic AB-glycotope, thus confirming our hypothesis. Moreover, similar antibodies were revealed in the blood of healthy blood group 0 donors. Analysis of spatial models was performed in addition to identify the hydroxyl groups of Fuc, Galα, and Galβ residues, which are particularly involved in the composition of the AB-glycotope.