Browsing by Author "Shikuma, Cecilia"

Now showing 1 - 2 of 2
  • Thumbnail Image
    Item
    Cystatin C based estimation of glomerular filtration rate and association with atherosclerosis imaging markers in people living with HIV
    (Wolters Kluwer, 2020-07) Mcclean, Mitchell; Buzkova, Petra; Budoff, Matthew; Estrella, Michelle; Freiberg, Matthew; Hodis, Howard N.; Palella, Frank; Shikuma, Cecilia; Post, Wendy S.; Gupta, Samir; Medicine, School of Medicine
    Introduction: Reduced estimated glomerular filtration rate (eGFR) is associated with increased risk of cardiovascular disease among people living with HIV (PLWH). It is unclear whether eGFR equations incorporating Cystatin C (CysC) measurements are more predictive of preclinical CVD than those using only creatinine (Cr). Objectives: The study aimed to determine which of the three Chronic Kidney Disease Epidemiology (CKD-EPI) eGFR equations is most associated with carotid intima media thickness (CIMT) and coronary artery calcium (CAC) score. Methods: This cross-sectional analysis of pooled data from three large cohorts compared the associations between the three CKD-EPI eGFR equations (Cr, CysC, and Cr-CysC) with CIMT and CAC score using multivariable regression analysis. eGFR and CIMT were analyzed as continuous variables. CAC scores were analyzed as a binary variable (detectable calcification versus nondetectable) and as a log10 Agatston score in those with detectable CAC. Results: 1487 participants were included, and of these 910 (562 HIV+, 348 HIV-) had CIMT measurements and 366 (296 HIV+, 70 HIV-) had CAC measurements available. In HIV- participants, GFR estimated by any CKD-EPI equation did not significantly correlate with CIMT or CAC scores. When PLWH were analyzed separately including HIV-specific factors, only GFR estimated using Cr-Cys C correlated with CIMT [β= -0.90, 95% CI (-1.67,-0.13) μm; p=0.023]. Similarly, eGFR correlated with Agatston scores only when using cystatin C-based eGFR [β= -8.63, 95% CI (-16.49,-0.77) HU; p=0.034]. Associations between other eGFR formulas and CAC did not reach statistical significance. Conclusion: In PLWH, preclinical atherosclerosis may be more closely correlated with eGFR using formulae that incorporate CysC measurements than Cr alone.
  • Thumbnail Image
    Item
    A high-affinity inhibitor of human CD59 enhances complement-mediated virolysis of HIV-1: implications for treatment of HIV-1/AIDS
    (The American Association of Immunologists, 2010-01-01) Hu, Weiguo; Yu, Qigui; Hu, Ningjie; Byrd, Daniel; Amet, Tohti; Shikuma, Cecilia; Shiramiz, Bruce; Halperin, Jose A.; Qin, Xuebin; Department of Microbiology and Immunology, IU School of Medicine
    Many pathogenic enveloped viruses, including HIV-1, escape complement-mediated virolysis by incorporating host cell regulators of complement activation into their own viral envelope. The presence of complement regulators including CD59 on the external surface of the viral envelope confers resistance to complement-mediated virolysis, which may explain why human pathogenic viruses such as HIV-1 are not neutralized by complement in human fluids, even in the presence of high Ab titers against the viral surface proteins. In this study, we report the development of a recombinant form of the fourth domain of the bacterial toxin intermedilysin (the recombinant domain 4 of intermedilysin [rILYd4]), a 114 aa protein that inhibits human CD59 function with high affinity and specificity. In the presence of rILYd4, HIV-1 virions derived from either cell lines or peripheral blood mononuclear cells of HIV-1-infected patients became highly sensitive to complement-mediated lysis activated by either anti-HIV-1 gp120 Abs or by viral infection-induced Abs present in the plasma of HIV-1-infected individuals. We also demonstrated that rILYd4 together with serum or plasma from HIV-1-infected patients as a source of anti-HIV-1 Abs and complement did not mediate complement-mediated lysis of either erythrocytes or peripheral blood mononuclear cells. These results indicate that rILYd4 may represent a novel therapeutic agent against HIV-1/AIDS.