Browsing by Subject "Erythrocyte"

Now showing 1 - 2 of 2
  • Thumbnail Image
    Item
    Association of erythrocyte n-3 polyunsaturated fatty acids with incident type 2 diabetes in a Chinese population
    (Elsevier, 2018-09-26) Zheng, Ju-Sheng; Lin, Jie-sheng; Dong, Hong-li; Zeng, Fang-fang; Li, Duo; Song, Yiqing; Chen, Yu-ming; Epidemiology, School of Public Health
    Summary Background & aims The association between circulating n-3 polyunsaturated fatty acid (PUFA) biomarkers and incident type 2 diabetes in Asian populations remains unclear. We aimed to examine the association of erythrocyte n-3 PUFA with incident type 2 diabetes in a Chinese population. Methods A total of 2671 participants, aged 40–75 y, free of type 2 diabetes at baseline, were included in the present analysis. Incident type 2 diabetes cases (n = 213) were ascertained during median follow-up of 5.6 years. Baseline erythrocyte fatty acids were measured by gas chromatography. We used multivariable Cox regression models to estimate the hazard ratios (HRs) and 95% confidence intervals (CIs) of type 2 diabetes across quartiles of erythrocyte n-3 PUFA. Results After adjustment for potential confounders, HRs (95% CIs) of type 2 diabetes were 0.68 (0.47, 1.00), 0.77 (0.52, 1.15), and 0.63 (0.41, 0.95) in quartiles 2–4 of docosapentaenoic acid (C22:5n-3) (P-trend = 0.07), compared with quartile 1; and 1.08 (0.74, 1.60), 1.03 (0.70, 1.51), and 0.57 (0.38, 0.86) for eicosapentaenoic acid (C20:5n-3) (P-trend = 0.007). No association was found for docosahexaenoic acid (C22:6n-3) or alpha-linolenic acid (C18:3n-3). Conclusions Erythrocyte n-3 PUFA from marine sources (C22:5n-3 and C20:5n-3), as biomarkers of dietary marine n-3 PUFA, were inversely associated with incident type 2 diabetes in this Chinese population. Future prospective investigations in other Asian populations are necessary to confirm our findings.
  • Thumbnail Image
    Item
    Erythrocytes from GGTA1/CMAH knockout pigs: implications for xenotransfusion and testing in non-human primates
    (Wiley, 2014-07) Wang, Zheng-Yu; Burlak, Christopher; Estrada, Jose L.; Li, Ping; Tector, Matthew F.; Tector, A. Joseph; Department of Surgery, IU School of Medicine
    Background Pig erythrocytes are potentially useful to solve the worldwide shortage of human blood for transfusion. Domestic pig erythrocytes, however, express antigens that are bound by human preformed antibodies. Advances in genetic engineering have made it possible to rapidly knock out the genes of multiple xenoantigens, namely galactose α1,3 galactose (aGal) and N-glycolylneuraminic acid (Neu5Gc). We have recently targeted the GGTA1 and CMAH genes with zinc finger endonucleases resulting in double knockout pigs that no longer express aGal or Neu5Gc and attract significantly fewer human antibodies. In this study, we characterized erythrocytes from domestic and genetically modified pigs, baboons, chimpanzees, and humans for binding of human and baboon natural antibody, and complement mediated lysis. Methods Distribution of anti Neu5Gc IgG and IgM in pooled human AB serum was analyzed by ELISA. Erythrocytes from domestic pigs (Dom), aGal knockout pigs (GGTA1 KO), aGal and Neu5Gc double knockout pigs (GGTA1/CMAH KO), baboons, chimpanzees, and humans were analyzed by flow cytometry for aGal and Neu5Gc expression. In vitro comparative analysis of erythrocytes was conducted with pooled human AB serum and baboon serum. Total antibody binding was accessed by hemagglutination; complement-dependent lysis was measured by hemolytic assay; IgG or IgM binding to erythrocytes was characterized by flow cytometry. Results The pooled human AB serum contained 0.38 μg/ml anti Neu5Gc IgG and 0.085 μg/ml anti Neu5Gc IgM. Both Gal and Neu5Gc were not detectable on GGTA1/CMAH KO erythrocytes. Hemagglutinaion of GGTA1/CMAH KO erythrocytes with human serum was 3.5-fold lower compared to GGTA1 KO erythrocytes, but 1.6-fold greater when agglutinated with baboon serum. Hemolysis of GGTA1/CMAH KO erythrocytes by human serum (25%) was reduced 9-fold compared to GGTA1 KO erythrocytes, but increased 1.64-fold by baboon serum. Human IgG binding was reduced 27-fold on GGTA1/CMAH KO erythrocytes compared to GGTA1 KO erythrocytes, but markedly increased 3-fold by baboon serum IgG. Human IgM binding was decreased 227-fold on GGTA1/CMAH KO erythrocytes compared to GGTA1 KO erythrocytes, but enhanced 5-fold by baboon serum IgM. Conclusions Removal of aGal and Neu5Gc antigens from pig erythrocytes significantly reduced human preformed antibody-mediated cytotoxicity but may have complicated future in vivo analysis by enhancing reactivity from baboons. The creation of the GGTA1/CMAH KO pig has provided the xenotransplantion researcher with organs and cells that attract fewer human antibodies than baboon and our closest primate relative, chimpanzee. These finding suggest that while GGTA1/CMAH KO erythrocytes may be useful for human transfusions, in vivo testing in the baboon may not provide a direct transplation to the clinic.