Two novel assays of alloantibody-secreting cells demonstrating resistance to desensitization with IVIG and rATG

D. K. Perry, H. S. Pollinger, J. M. Burns, D. Rea, E. Ramos, J. L. Platt, J. M. Gloor, M. D. Stegall

Research output: Contribution to journalArticle

58 Scopus citations

Abstract

Donor-specific alloantibody presents a major barrier to the successful transplantation of kidneys and hearts. However, the study of alloantibody production has been hampered by both an inadequate source of antibody-secreting cells (ASCs) and a paucity of assays to determine their function. We describe two new assays that allow for the determination of the frequency and specificities of allo-ASCs in humans using purified HLA as targets. These assays demonstrated allo-ASCs in the CD138+ fraction of the bone marrow, but not in peripheral blood. Alloantibody specificities in these assays correlated well with those detected in the serum suggesting that bone marrow-derived ASCs are indeed a major source of alloantibody in vivo. However, ASCs for a specific HLA antigen were rare with an estimated frequency of only 1/2 × 106 marrow cells. Pretransplant treatment in vivo with multiple plasmaphereses and low-dose IVIG alone or in combination with rATG had no effect on ASC number or alloantibody production. These techniques allow for the study of allospecific ASCs and provide a method to test the potential efficacy of agents on alloantibody production in vivo.

Original languageEnglish (US)
Pages (from-to)133-143
Number of pages11
JournalAmerican Journal of Transplantation
Volume8
Issue number1
DOIs
StatePublished - Jan 1 2008

Keywords

  • Alloantibody
  • HLA
  • Kidney transplant
  • Plasma cell
  • rATG

ASJC Scopus subject areas

  • Immunology and Allergy
  • Transplantation
  • Pharmacology (medical)

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