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The central region of the human major histocompatibility complex contains tandemly arranged genes of RP, C4, CYP21, and TNX. The C4 gene region is prone to rearrangements that generates duplications, conversions, and deletions. Diversity in gene number and size causes reorganization and may lead to genetic disorders. The RP, C4, CYP21, and TNX genes form a genetic unit called RCCX. We describe molecular studies on RCCX haplotypes revealing a unique recombination giving rise to a TNXB/TNXA hybrid gene, CYP21A deletion and CYP21B duplication on one chromosome of the propositus. His other chromosome carries a deletion of CYP21A-TNXA-RP2-C4B genes, resulting in the total absence of CYP21A genes and the presence of three CYP21B genes in the genome. [Copyright &y& Elsevier]

Tyrosine kinase inhibitors have greatly improved the prognosis of chronic myeloid leukemia (CML). In addition to direct kinase inhibition, their effects can also be mediated through immune modulation, such as expansion of cytotoxic T and natural-killer cells observed during dasatinib therapy. As natural-killer cell and partially CD8+ T-cell function are regulated by killer immunoglobulin-like receptors (KIRs), we studied whether the KIR gene profile is associated with clinical therapy response in dasatinib-treated CML patients (n = 191). In first-line patients, the absence of the inhibitory KIR2DL5A (p = 0.0489), 2DL5B (p = 0.030), and 2DL5all (p = 0.0272) genes were associated with improved molecular response at the 12-month time point. In addition, the same trend was seen with two activating KIR genes, 2DS1 (p = 0.061) and 2DS2 (p = 0.071). Furthermore, when patients were clustered into two groups by their KIR gene profile, the BCR-ABL1 transcript levels differed significantly between the groups (p = 0.047), showing that patients who lacked several KIR genes had better response. The comparison of first-line and second-line patients did not show any significant differences in either KIR or human leukocyte antigen genotypes. Our results show that immunogenetic factors, such as the KIR gene profile, can play a role in tyrosine kinase inhibitor therapy response. Additional studies are warranted to elucidate the functional significance of KIR genes associated with treatment outcomes. [ABSTRACT FROM AUTHOR]

Long cold ischemia time (CIT) is the most important factor contributing to delayed graft function (DGF) after kidney transplant. Improvements in pretransplant procedures may reduce CIT and improve clinical outcome. Pretransplant histocompatibility tests were modernized at our laboratory in 2015, leading to significant decrease of time consumed for these enabling earlier surgery. The effects of this on kidney transplant CIT, DGF, and other clinical outcomes were studied. The study population consisted of 896 consecutive deceased donor kidney recipients, of which 442 patients received a transplant with the old crossmatch and 454 received a transplant with the new crossmatch. CIT shortened from mean 20 hours 6 minutes to 15 hours 52 minutes (P <.001). The incidence of DGF was significantly reduced from 31% to 24% (P =.02). Reduction in the frequency of DGF was more pronounced among the highly sensitized patients (53% to 28%, P =.01) or in patients with pretransplant donor-specific antibodies (50% to 20%, P =.002) and among patients who received kidneys from donors older than 65 years (38% to 27%, P =.04). Process optimization that reduces CIT decreases occurrence of DGF, especially in highly sensitized patients and patients who receive kidneys from older donors. [ABSTRACT FROM AUTHOR]

Objective: Cell surface glycans contribute to the adhesion capacity of cells and are essential in cellular signal transduction. Yet, the glycosylation of hematopoietic stem and progenitor cells (HSPC), such as CD133+ cells, is poorly explored. Materials and Methods: N-glycan structures of cord blood–derived CD133+ and CD133− cells were analyzed with mass spectrometric profiling and exoglycosidase digestion, cell surface glycan epitopes with lectin binding assay, and expression of N-glycan biosynthesis-related genes with microarray analysis. Results: Over 10% difference was demonstrated in the N-glycan profiles of CD133+ and CD133− cells. Biantennary complex-type N-glycans were enriched in CD133+ cells. Of the genes regulating the synthesis of these structures, CD133+ cells overexpressed MGAT2 and underexpressed MGAT4. Moreover, the amount of high-mannose type N-glycans and terminal α2,3-sialylation was increased in CD133+ cells. Elevated α2,3-sialylation was supported by the overexpression of ST3GAL6. Conclusion: Our work presents new information on the characters of HSPCs. The new knowledge of HSPC-specific N-glycosylation advances their identification and provides tools to promote HSPC homing and mobilization or targeting to specific tissues. [Copyright &y& Elsevier]