Preformed circulating HLA-specific memory B cells predict high risk of humoral rejection in kidney transplantation

Kidney Int. 2015 Oct;88(4):874-87. doi: 10.1038/ki.2015.205. Epub 2015 Jul 15.


The accurate evaluation of donor-specific antibodies (DSAs) has allowed a precise identification of sensitized patients at risk of antibody-mediated rejection (ABMR). However, the scale of the humoral response is not always fully addressed, as it excludes the complete memory B-cell (mBC) pool such as that caused by antigen-specific mBC. Using a novel B-cell ELISpot assay approach, we assessed circulating mBC frequencies against class I and II HLA antigens in highly sensitized and nonsensitized patients in the waiting list for kidney transplantation. Also, kidney transplant patients undergoing ABMR were evaluated for the presence of donor-specific mBCs both at the time of rejection and before transplantation. For this purpose, 278 target HLA-sp antigens from 70 patients were studied and compared to circulating HLA-sp antibodies. Both class I and II HLA-sp mBC frequencies were identified in highly sensitized individuals but not in nonsensitized and healthy individuals, many years after first sensitization. Also, high donor-specific mBC responses were clearly found both during ABMR and before transplantation, regardless of circulating DSA. The higher the donor-specific mBC response, the more aggressive the allograft rejection. Thus, assessing donor-specific mBC frequencies may be relevant to better refine patient alloimmune-risk stratification, and provides new insight into the mechanisms of the adaptive humoral alloimmune response taking place in kidney transplantation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Allografts
  • B-Lymphocytes / immunology*
  • Biomarkers / blood
  • Case-Control Studies
  • Enzyme-Linked Immunospot Assay
  • Female
  • Graft Rejection / diagnosis
  • Graft Rejection / immunology*
  • HLA Antigens / blood*
  • Histocompatibility Testing
  • Histocompatibility*
  • Humans
  • Immunity, Humoral*
  • Immunologic Memory*
  • Isoantibodies / blood*
  • Kidney Transplantation / adverse effects*
  • Male
  • Middle Aged
  • Predictive Value of Tests
  • Risk Assessment
  • Risk Factors
  • Time Factors
  • Treatment Outcome
  • Waiting Lists


  • Biomarkers
  • HLA Antigens
  • Isoantibodies