POSSIBLE APPLICATIONS OF UMBILICAL CORD BLOOD HEMATOPOIETIC STEM CELLS WITH CCR5-DELTA 32/DELTA 32 GENOTYPE FOR THE TREATMENT OF HIV INFECTION

DOI: https://doi.org/None

A.B. Smolyaninov (1,2), A.V. Chechetkin (3), I.A. Pirozhkov (1,2), D.A. Ivolgin (1,2) 1 -Stem cell bank «Pokrovsky», Bolshoi Prospect Vasilevskоgo Ostrova, 85, Saint-Petersburg, 199026, Russian Federation; 2 -Research Laboratory of cell technologies of the North-West State Medical University named after I.I. Mechnikov, Kirochnaya street, 41, Saint-Petersburg, 191015, Russian Federation; 3 -Russian Research Institute of Hematology and Transfusiology of the Russian Federal Medical-biological Agency, 2 Sovetskaya Street, 16, Saint-Petersburg, 193024, Russian Federation

Introduction. Binding of the human immunodeficiency virus (HIV) envelope gp120 glycoprotein to CD4 and CCR5 receptors on the cell membrane initiates the viral entry process. Simultaneous expression of these two receptors has been observed on T-lymphocytes, monocytes, macrophages and dendritic cells. There is lost-of-function mutation of CCR5 gene representing a 32 base deletion in the coding region of the gene. Homozygous carriers of the CCR5-delta 32/delta 32 mutation are resistant to HIV infection because the mutation prevents the functional expression of the CCR5 receptor. Perspectives of using umbilical cord blood for the management of HIV infection are associated with the possibility of umbilical cord blood hematopoietic stem cell transplantation to HIV-infected patients from homozygous carriers of the CCR5-delta 32 mutation. The aim of study. The examination of cord blood samples for CCR5-delta 32 polymorphism detection and HLA-typing and characterization of the number of nucleated cells of these samples. Methods. Molecular genetic study for CCR5 polymorphism was performed by polymerase chain reaction. HLA-typing was performed by SSP (sequence-specific priming) method. The number of nucleated cells was determined by using hematology analyzer. CD34+-cells number was measured by flow cytometry method. Results. There were investigated 3860 umbilical cord blood samples. We found 39 CCR5-delta 32/delta 32 samples (1,01%), 707 heterozygous CCR5-delta 32 samples (18,32%). There was found a high prevalence of the most common HLA-alleles in north-west Russia among umbilical cord blood donors. Conclusion. As a result of the study there was determined the frequency of allele CCR5-delta 32 in the North-West region of Russia, correlated with data on the distribution of this polymorphism in Europe. Detected by screening CCR5-delta 32/delta 32 samples will allow to organize own regional public repository of such samples of umbilical cord blood.
Keywords: 
umbilical cord blood, human immunodeficiency virus, CCR5-delta 32, hematopoietic stem cell transplantation

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