Early emergence of anti-HCV antibody implicates donor origin in recipients of an HCV-infected organ

Am J Transplant. 2019 Sep;19(9):2525-2532. doi: 10.1111/ajt.15415. Epub 2019 May 28.

Abstract

Hepatitis C virus (HCV) seroconversion among HCV-uninfected transplant recipients from HCV-infected (NAT+/Antibody+) or HCV-exposed (NAT-/Antibody+) donors has been reported. However, the origin of anti-HCV antibody and the implications of seroconversion remain unknown. We longitudinally tested plasma from HCV-uninfected kidney (n = 31) or heart transplant recipients (n = 9) of an HCV NAT+ organ for anti-HCV antibody (both IgG and IgM isotypes). Almost half of all participants had detectable anti-HCV antibody at any point during follow-up. The majority of antibody-positive individuals became positive within 1-3 days of transplantation, and 6 recipients had detectable antibody on the first day posttransplant. Notably, all anti-HCV antibody was IgG, even in samples collected posttransplant day 1. Late seroconversion was uncommon (≈20%-25% of antibody+ recipients). Early antibody persisted over 30 days in kidney recipients, whereas early antibody dropped below detection in 50% of heart recipients within 2 weeks after transplant. Anti-HCV antibody is common in HCV-uninfected recipients of an HCV NAT+ organ. The IgG isotype of this antibody and the kinetics of its appearance and durability suggest that anti-HCV antibody is donor derived and is likely produced by a cellular source. Our data suggest that transfer of donor humoral immunity to a recipient may be much more common than previously appreciated.

Keywords: antibody biology; clinical research/practice; donor-derived infections; donors and donation; hepatitis C; infection and infectious agents - viral; kidney transplantation/nephrology; translational research/science.

Publication types

  • Clinical Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Female
  • Heart Failure / complications
  • Heart Failure / surgery*
  • Heart Failure / virology
  • Heart Transplantation / adverse effects*
  • Hepacivirus
  • Hepatitis C / transmission*
  • Hepatitis C Antibodies / blood*
  • Hepatitis C Antibodies / immunology
  • Humans
  • Immunoglobulin G / blood
  • Immunoglobulin G / immunology
  • Immunoglobulin M / blood
  • Immunoglobulin M / immunology
  • Immunosuppression Therapy
  • Kidney Failure, Chronic / complications
  • Kidney Failure, Chronic / surgery*
  • Kidney Failure, Chronic / virology
  • Kidney Transplantation / adverse effects*
  • Longitudinal Studies
  • Male
  • Middle Aged
  • Postoperative Complications
  • Risk Factors
  • Tissue and Organ Procurement
  • Transplant Recipients
  • Viral Load

Substances

  • Hepatitis C Antibodies
  • Immunoglobulin G
  • Immunoglobulin M