title: Two novel assays of alloantibody-secreting cells demonstrating resistance to desensitization with IVIG and rATG.
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 x 10(6) 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.
authors.affiliation: Department of Surgery, Division of Transplantation, and von Liebig Transplant Center, Mayo Clinic College of Medicine, Rochester, MN, USA.
authors.forename: D K
authors.initials: DK
authors.lastname: Perry
authors.forename: H S
authors.initials: HS
authors.lastname: Pollinger
authors.forename: J M
authors.initials: JM
authors.lastname: Burns
authors.forename: D
authors.initials: D
authors.lastname: Rea
authors.forename: E
authors.initials: E
authors.lastname: Ramos
authors.forename: J L
authors.initials: JL
authors.lastname: Platt
authors.forename: J M
authors.initials: JM
authors.lastname: Gloor
authors.forename: M D
authors.initials: MD
authors.lastname: Stegall
mesh_terms: D000328:Adult; D000368:Aged; D000921:Antibody-Producing Cells / Q000276:immunology* / Q000378:metabolism; D000961:Antilymphocyte Serum / Q000276:immunology*; D002478:Cells, Cultured; D003888:Desensitization, Immunologic; D005260:Female; D006801:Humans; D016756:Immunoglobulins, Intravenous; D007518:Isoantibodies / Q000096:biosynthesis*; D008297:Male; D008875:Middle Aged
chemical_list: D000961:Antilymphocyte Serum; D016756:Immunoglobulins, Intravenous; D007518:Isoantibodies