title: Specificity and Ig class of preformed alloantibodies causing a positive crossmatch in renal transplantation. The implications for graft survival.
abstract: Sixty-five kidney transplantations performed across a non-current alloantibody-positive T cell crossmatch or an alloantibody-positive B cell crossmatch were studied retrospectively. The DTT crossmatch was used to discriminate between IgM and IgG donor-reactive antibodies. Subsequently the HLA specificity of donor-reactive IgG antibodies was determined in the MAILA assay. The first transplantations performed across a non-current positive T cell DTT crossmatch (IgG) were associated with poor graft survival, as only 5 of 11 (45%) transplants were functioning at 1 year. The HLA specificity of donor T cell reactive IgG antibodies appeared to determine the fate of the graft: only 2 of 7 (29%) patients with donor HLA class I-reactive antibodies had functioning grafts at 1 year, whereas all 3 patients with donor T cell-reactive antibodies, lacking HLA specificity, had functioning grafts. In 17 first transplantations, 15 grafts (88%) transplanted across an IgM-positive B cell crossmatch were functioning at 1 year. In 9 re-transplantations we found 6 grafts (67%) functioning at 1 year. B cell-reactive IgG antibodies, however, were associated with poor graft survival. In 7 first transplantations 2 grafts (29%) were functioning at 1 year, and in 17 re-transplantations 8 grafts (47%) were functioning at 1 year. For 19 patients the HLA specificity of donor B cell-reactive IgG antibodies was determined. Thirteen patients had HLA class II (-DR and/or -DQ)--specific antibodies; of these, 4 (31%) had a functioning graft at 1 year. Two of 3 (67%) patients with weak HLA class I--reactive antibodies and 2 of 3 (67%) patients with B cell--reactive IgG antibodies without HLA specificity had a functioning graft at 1 year. Although the number of cases analyzed is small, the following conclusions can be drawn: First, in general, the presence of donor HLA class I-, HLA-DR-, and HLA-DQ-reactive IgG antibodies is a contraindication to transplantation. However, under certain so-far-unknown conditions, transplantation across donor-reactive HLA specific IgG alloantibodies might be possible. Second, renal transplantation can be safely performed across B cell-reactive IgM antibodies. Third, donor-reactive IgG antibodies that do not recognize HLA do not seem to be harmful.
authors.affiliation: Laboratory for Transplantation Serology, Radboud University Hospital, Nijmegen, The Netherlands.
authors.forename: G M
authors.initials: GM
authors.lastname: ten Hoor
authors.forename: M
authors.initials: M
authors.lastname: Coopmans
authors.forename: W A
authors.initials: WA
authors.lastname: Allebes
mesh_terms: D000918:Antibody Specificity; D001402:B-Lymphocytes / Q000276:immunology; D000939:Epitopes; D006085:Graft Survival / Q000276:immunology*; D006680:HLA Antigens / Q000276:immunology; D006650:Histocompatibility Testing; D006801:Humans; D007074:Immunoglobulin G / Q000032:analysis / Q000276:immunology*; D007075:Immunoglobulin M / Q000032:analysis / Q000276:immunology*; D007136:Immunoglobulins / Q000145:classification; D007518:Isoantibodies / Q000032:analysis / Q000145:classification / Q000276:immunology*; D016030:Kidney Transplantation / Q000276:immunology*; D011237:Predictive Value of Tests; D012189:Retrospective Studies; D013601:T-Lymphocytes / Q000276:immunology; D014019:Tissue Donors
chemical_list: D000939:Epitopes; D006680:HLA Antigens; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D007136:Immunoglobulins; D007518:Isoantibodies