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Viral Induced Changes in Gene Expression in the Urine of Children with BKV Cystitis

Urbanski, Annette
http://rave.ohiolink.edu/etdc/view?acc_num=ucin1649762002751981

Abstract Details

2022, MS, University of Cincinnati, Medicine: Biomedical Research Technology.
Background Viral reactivation is a nearly universal occurrence for children undergoing hematopoietic stem cell transplantation. (HSCT). HSCT removes the BKV specific T-cells that control BKV, resulting in the reactivation of BKV. BKV reactivation puts HSCT recipients at an increased risk for serious transplant complications, including graft vs. host disease (GVHD), thrombotic microangiopathy (TMA), and most notably, hemorrhagic cystitis (HC). Previous research has shown that anti-BKV directed T-cells generated ex vi-vo can control BKV, but this therapy is not widely available. In addition, without animal models and without direct access to bladder tissue, understanding of mechanisms of cystitis is very limited. We hypothesize that shed urothelial cells derived from urine can be used as a source of material for the investigation of individual susceptibility to BKV cystitis and that differences in innate immunity in the urothelium regulate risk of cystitis in children undergoing HSCT. Methods Urine samples were collected prospectively from children receiving HSCT once weekly starting prior to HSCT through 100 days after stem cell infusion, aliquoted, and stored at -80 C. Prospective systematic sample collection irrespective of clinical status, allowed the unbiased collection of a bank of cases of cystitis together with controls with viruria and no cystitis and controls with neither high-level viruria nor cystitis that are immediately available for study. Morphological and gene expression studies of urine sediment were used to determine host differences in viral sensors and APOBECs that may influence the risk of cystitis by studying shed urothelium from clinical urine samples. Results The morphology supported our hypothesis that most cells that we see in the urinary sediment are of urothelial origin and are suitable for study. APOBEC3B was significantly higher in those with BK viruria levels above the median as compared to those with BK viruria below the median, a Ct value of 16.6 versus 36.6 (p=0.028). In patients with viruria we saw increased expression of CXCL10 in those with viruria greater than the median (Ct median 15.3) compared with those with viruria less than median (median Ct value of 36, the cutoff for absent expression), (p=0.008). Similarly, with expression of IFNb, we saw a median Ct value of 16.8 in those with BK viruria less than the median and 14 in those with viruria greater than the median (p= 0.06). Conclusion We have identified urine sediment to be an appropriate source of cells to study for inflammation of the bladder. Our data indicate an important role for APOBEC3A in regulation of cystitis. This is an im-portant observation because APOBEC3A is inducible, suggesting that we could develop a medication that would induce expression of APOBECS to protect against future cystitis
Stella Davies, Ph.D. (Committee Member)
Pooja Khandelwal, M.D. (Committee Member)
John Brewington (Committee Member)
16 p.
Surgery
BK; Urine Sediment; Hemorrhagic Cystitis; Viruria; APOBEC3; Viremia

Recommended Citations

Citations

  • Urbanski, A. (2022). Viral Induced Changes in Gene Expression in the Urine of Children with BKV Cystitis [Master's thesis, University of Cincinnati]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1649762002751981

    APA Style (7th edition)

  • Urbanski, Annette. Viral Induced Changes in Gene Expression in the Urine of Children with BKV Cystitis. 2022. University of Cincinnati, Master's thesis. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=ucin1649762002751981.

    MLA Style (8th edition)

  • Urbanski, Annette. "Viral Induced Changes in Gene Expression in the Urine of Children with BKV Cystitis." Master's thesis, University of Cincinnati, 2022. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1649762002751981

    Chicago Manual of Style (17th edition)

ucin1649762002751981
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© 2022, some rights reserved.Creative Commons License Viral Induced Changes in Gene Expression in the Urine of Children with BKV Cystitis by Annette Urbanski is licensed under a Creative Commons Attribution-NonCommercial-NoDerivs 3.0 Unported License. Based on a work at etd.ohiolink.edu.
This open access ETD is published by University of Cincinnati and OhioLINK.