High mean fluorescence intensity donor-specific anti-HLA antibodies associated with chronic rejection postliver transplant

J. G. O'Leary, H. Kaneku, B. M. Susskind, L. W. Jennings, M. A. Neri, G. L. Davis, G. B. Klintmalm, P. I. Terasaki

Research output: Contribution to journalArticle

112 Scopus citations

Abstract

In contrast to kidney transplantation where donor-specific anti-HLA antibodies (DSA) negatively impact graft survival, correlation of DSA with clinical outcomes in patients after orthotopic liver transplantation (OLT) has not been clearly established. We hypothesized that DSA are present in patients who develop chronic rejection after OLT. Prospectively collected serial serum samples on 39 primary OLT patients with biopsy-proven chronic rejection and 39 comparator patients were blinded and analyzed for DSA using LABScreen® single antigen beads test, where a 1000 mean fluorescence value was considered positive. In study patients, the median graft survival was 15 months, 74% received ≥ one retransplant, 20% remain alive and 87% had ≥ one episode of acute rejection. This is in contrast to comparator patients where 69% remain alive, and no patient needed retransplant or experienced rejection. Thirty-six chronic rejection patients (92%) and 24 (61%) comparator patients had DSA (p = 0.003). Chronic rejection versus comparator patients had higher mean fluorescence intensity (MFI) DSA. Although a further study with larger numbers of patients is needed to identify clinically significant thresholds, there is an association of high-MFI DSA with chronic rejection after OLT. Serial serum samples from 39 chronic rejection and 39 comparator liver transplant recipients show a strong association between donor-specific antibody and chronic rejection, and the effects of preformed donor class I specific antibody can be mitigated by antibody induction therapy. See editorial by Briggs and Adams on page 1767.

Original languageEnglish (US)
Pages (from-to)1868-1876
Number of pages9
JournalAmerican Journal of Transplantation
Volume11
Issue number9
DOIs
StatePublished - Sep 1 2011

Keywords

  • Chronic allograft rejection
  • HLA antibodies
  • Liver Transplantation
  • donor-specific antibodies

ASJC Scopus subject areas

  • Immunology and Allergy
  • Transplantation
  • Pharmacology (medical)

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