title: Anti-HLA donor-specific antibodies detected in positive B-cell crossmatches by Luminex predict late graft loss.
abstract: The significance of B-cell crossmatching in kidney transplantation is controversial. Recipients (n = 471) transplanted in a single centre from 1987 to 2005 with complete T- and B-cell crossmatch records were studied. Sera from 83 patients transplanted across a positive B-cell crossmatch, with concomitant negative T-cell crossmatch (T-B+) on either current and/or peak sera were studied using Luminex to determine presence of donor-specific antibodies (DSA). Clinical outcomes of T-B+ patients were compared with 386 T-B- patients. T-B+ predicted vascular (p = 0.01), but not cellular (p = 0.82) or glomerular (p = 0.14) rejection. IgG HLA DSA were found in 33% (n = 27) of the T-B+ patients and were associated with higher risk of any (p = 0.047), vascular (p = 0.01) or glomerular (p < 0.001) rejection at 6 months. Of 27 patients with DSA, 18/21 (86%) were the complement-fixing IgG(1) and/or IgG(3) subclass antibodies. DSA imposed a statistically significant higher risk of graft loss 5 years posttransplant (1.8 [1.0-3.3], p = 0.045). This study showed that only one-third of positive B-cell crossmatch (BXM) was caused by DSA and was associated with late graft loss. Thus, using BXM to preclude kidney transplantation may potentially disadvantage >60% of patients in whom BXM is not indicative of the presence of DSA.
authors.affiliation: Department of Medicine, University of Adelaide, Adelaide, South Australia, Australia.
authors.forename: H S
authors.initials: HS
authors.lastname: Eng
authors.forename: G
authors.initials: G
authors.lastname: Bennett
authors.forename: E
authors.initials: E
authors.lastname: Tsiopelas
authors.forename: M
authors.initials: M
authors.lastname: Lake
authors.forename: I
authors.initials: I
authors.lastname: Humphreys
authors.forename: S H
authors.initials: SH
authors.lastname: Chang
authors.forename: P T H
authors.initials: PT
authors.lastname: Coates
authors.forename: G R
authors.initials: GR
authors.lastname: Russ
mesh_terms: D000918:Antibody Specificity; D000961:Antilymphocyte Serum / Q000276:immunology; D001323:Autoantibodies / Q000737:chemistry; D001402:B-Lymphocytes / Q000276:immunology / Q000378:metabolism*; D005919:Glomerular Filtration Rate; D006084:Graft Rejection / Q000175:diagnosis*; D006085:Graft Survival; D006680:HLA Antigens / Q000737:chemistry*; D015395:Histocompatibility Antigens Class I; D000949:Histocompatibility Antigens Class II; D006650:Histocompatibility Testing / Q000379:methods*; D006801:Humans; D016130:Immunophenotyping; D016030:Kidney Transplantation / Q000379:methods*; D013601:T-Lymphocytes / Q000276:immunology
chemical_list: D000961:Antilymphocyte Serum; D001323:Autoantibodies; D006680:HLA Antigens; D015395:Histocompatibility Antigens Class I; D000949:Histocompatibility Antigens Class II