title: Soluble donor DNA and islet injury after transplantation.
abstract: BACKGROUND
  A large proportion of clinical islet transplant recipients fail to initially achieve or sustain meaningful independence from exogenous insulin use. We hypothesized that immediate allograft injury is a key constraint on independence from exogenous insulin use.
  
  
  METHODS
  Standard human leukocyte antigen genotyping was reviewed to identify nonshared polymorphisms between 21 prospectively recruited islet transplant recipients from a single institution and their respective donors. Human leukocyte antigen polymorphism-specific quantitative polymerase chain reaction was used to quantify donor DNA shed into blood by injured islets from serial sera acquired over the first 10 days postprocedure and examined for correlation with achievement of insulin independence.
  
  
  RESULTS
  Nearly fourfold higher serum concentrations of donor DNA were detected in subjects whose grafts failed to generate insulin independence. The median for the average area under the curve in recipients who did and did not achieve insulin independence was 12 (range, 1-61) and 45 (range, 14-255) donor genome equivalents (gEq)-day/mL (p=0.03), respectively.
  
  
  CONCLUSIONS
  These findings represent the first direct testing of allograft injury in humans undergoing islet cell transplantation. Injury to donor islets very soon after transplantation may represent an important barrier to achieving insulin independence other than adaptive immune responses targeting allografts at later times. In addition, soluble donor DNA merits further development as a quantifiable biomarker to evaluate new interventions aimed at mitigating immediate islet injury.
authors: Clinical Research Division, Fred Hutchinson Cancer Research Center, 1100 Fairview Ave N., Seattle, WA 98109, USA. vkgadi@uw.edu
authors: Vijayakrishna K
authors: VK
authors: Gadi
authors: J Lee
authors: JL
authors: Nelson
authors: Katherine A
authors: KA
authors: Guthrie
authors: Colin C
authors: CC
authors: Anderson
authors: Nicholas D
authors: ND
authors: Boespflug
authors: Jeffrey W
authors: JW
authors: Redinger
authors: Biswajit
authors: B
authors: Paul
authors: Parastoo
authors: P
authors: Dinyari
authors: A M James
authors: AM
authors: Shapiro
mesh_terms: D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000097:blood; D004247:DNA / Q000097:blood* / Q000235:genetics; D003922:Diabetes Mellitus, Type 1 / Q000601:surgery; D005260:Female; D005838:Genotype; D006680:HLA Antigens / Q000235:genetics; D006801:Humans; D007515:Islets of Langerhans / Q000293:injuries*; D016381:Islets of Langerhans Transplantation / Q000009:adverse effects*; D008297:Male; D008875:Middle Aged; D011183:Postoperative Complications / Q000209:etiology; D011446:Prospective Studies; D012995:Solubility; D014019:Tissue Donors
chemical_list: D015415:Biomarkers; D006680:HLA Antigens; D004247:DNA