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Background: A number of alleles have been described for ABO encoding for common and rare ABO blood group phenotypes. Critical mutations in the coding sequence of ABO that may confer the different specificity and activity of the glycosyltransferases encoded by this gene locus have been identified.Study Design and Methods: Three unrelated patients from Germany, Turkey, and Bosnia who were diagnosed as having variant A subgroups were subjected to extended ABO typing. Serologic investigations were performed with standard methods. The genetic basis of the ABO phenotypes was determined by haplotype-specific sequence analysis of the last two exons (exons 6 and 7) of ABO and the intervening intron.Results: The RBCs of all three patients showed serologic A characteristics being similar to subgroup A(x). The serum of all three patients contained weakly reactive anti-A. In all three patients, sequence analysis indicated an A allele with a nucleotide sequence identical to ABO(*)A101 except for a single-base substitution in exon 7 at position 502, where C was replaced by G. This point mutation resulted in an amino acid exchange from arginine to glycine at position 168. The nucleotide sequence of intron 6 of the A allele was found to be identical to the ABO(*)A101 sequence in each patient.Conclusion: This study suggests that a variant A phenotype can arise from the new R168G polymorphism, reflecting the importance of this region for the ABO transferase efficiency. [ABSTRACT FROM AUTHOR]

AbstractDendritic cell (DC)-based immunization is a potent strategy to direct prompt and durable immune responses against viral reactivations after transplantations. Here, we show that overnight lentiviral vector (LV) gene transfer into human monocytes co-expressing granulocyte-macrophage colony stimulating factor and interleukin (IL)-4 induced self-differentiated DCs (SMART-DCs) with stable DC immunophenotype over weeks in culture and secreted several inflammatory cytokines. SMART-DCs injected subcutaneously in immunodeficient NOD.Rag1−/−.IL2rγ−/−(NRG) mice 1 day after LV transduction were stable for a month in vivo. “Conventional” DCs (cDCs) and SMART-DCs were compared with regard to their potency to accelerate the expansion, biodistribution, and antigenic stimulation of autologous human T cells. Peripheral blood cells obtained from human cytomegalovirus (hCMV)-reactive donors and full-length hCMV pp65 antigenic protein or peptides were used. DCs loaded with pp65 were administered subcutaneously into NRG mice as a preconditioning treatment a week prior to intravenous infusion with T cells. Optical imaging analyses demonstrated that in mice preconditioned with SMART-DC-pp65, T cells were directly recruited to the immunization site and subsequently spread to the spleen and other organs. A dramatic expansion of both human CD8+and CD4+T cells could be observed within a few days after infusion, and this was associated with consistent measurable CD8+effector memory T-cell responses against different pp65 epitopes. Thus, this mouse model demonstrates the proof-of-principle for SMART-DCs to accelerate expansion of human lymphocytes, resulting in poly-functional and antigen-specific immune responses against hCMV-pp65. [ABSTRACT FROM AUTHOR]