Immunosuppression with mTOR inhibitors prevents the development of donor-specific antibodies after liver transplant

Clin Transplant. 2017 Jun;31(6). doi: 10.1111/ctr.12974. Epub 2017 Apr 16.

Abstract

Background: Donor-specific antibodies (DSAs) are an important cause of complications after solid organ transplant. Risk factors and, thus, strategies for preventing DSA development are not well defined.

Methods: The DSA status of 400 patients who underwent liver transplant (LT) at the outpatient clinic of the University Hospital Essen was determined. Human leukocyte antigen (HLA) antibodies were detected by single-antigen bead technology. The strength of DSAs was reported as mean fluorescence intensity.

Results: Detectable DSAs were found in 74 (18.5%) patients and significantly more often in patients who underwent LT for autoimmune liver disease than for all other indications (29.3%; P=.022), but significantly less often found in patients who underwent LT for hepatocellular carcinoma (7.6%, P=.005). The incidence of DSAs increased with time after LT, and the risk was generally higher for female patients. The frequency of DSA detection was significantly lower (10.6%) for patients receiving immunosuppressive treatment with mammalian target of rapamycin (mTOR) inhibitors than for those receiving other regimens (20.5%; P=.025).

Conclusion: Autoimmune liver diseases, female sex, and time of more than 8 years since LT predispose patients to the development of DSAs. Immunosuppression with the mTOR inhibitor everolimus protects against DSA development after liver transplant.

Keywords: donor-specific antibodies; everolimus; hepatocellular carcinoma; human leukocyte antigen antibodies; liver transplantation.

MeSH terms

  • Female
  • Follow-Up Studies
  • Graft Rejection / blood
  • Graft Rejection / drug therapy*
  • Graft Rejection / etiology
  • Graft Survival
  • Humans
  • Immunosuppressive Agents / pharmacology*
  • Isoantibodies / blood*
  • Liver Transplantation / adverse effects*
  • Male
  • Middle Aged
  • Postoperative Complications
  • Prognosis
  • Retrospective Studies
  • Risk Factors
  • TOR Serine-Threonine Kinases / antagonists & inhibitors*
  • Tissue Donors*

Substances

  • Immunosuppressive Agents
  • Isoantibodies
  • MTOR protein, human
  • TOR Serine-Threonine Kinases