title: The differential pathogenicity of HLA antibodies: what a large cross-sectional study can tell us.
abstract: Despite remarkable advances in kidney transplantation over the past decades, allograft dysfunction remains the major barrier to long-term survival. With the advent of more powerful diagnostic tools, antibody-mediated processes became a major focus of interest. The differential pathogenicity of human leukocyte antigen antibodies (HLAab) is still not well understood. Therefore, the aim of this study was to evaluate the potential of determining the complement-binding capability and immunoglobulin G (IgG) subclass of HLAab posttransplant to predict long-term renal allograft outcome. In a large single-center study, we enrolled serum samples of 788 kidney transplants that were tested in a cross-sectional manner for the presence of HLAab by Luminex solid-phase assay. Graft function survival was followed for 8 years after antibody testing. We established and validated two modifications to the standard Luminex assay in order to further delineate the antibody effector function by detecting complement Clq binding and IgG subclass composition. HLAab, in particular those with donor-specificity, could be associated with decreased kidney allograft survival. The assessment of the complement-binding ability rather than IgG subclass composition pattern of HLAab significantly enhanced the predictive value. In conclusion, the predictive value of detecting Clq-binding capability provides further perspectives for patient risk stratification to improve long-term renal allograft outcome.
authors.forename: Nils
authors.initials: N
authors.lastname: Lachmann
authors.forename: Constanze
authors.initials: C
authors.lastname: Schönemann
mesh_terms: D015331:Cohort Studies; D015922:Complement C1q / Q000276:immunology; D003430:Cross-Sectional Studies; D006084:Graft Rejection / Q000453:epidemiology / Q000209:etiology / Q000276:immunology*; D006680:HLA Antigens / Q000276:immunology*; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology*; D015994:Incidence; D007518:Isoantibodies / Q000276:immunology*; D016030:Kidney Transplantation / Q000009:adverse effects* / Q000706:statistics & numerical data; D012307:Risk Factors; D016036:Seroepidemiologic Studies; D014184:Transplantation, Homologous
chemical_list: D006680:HLA Antigens; D007074:Immunoglobulin G; D007518:Isoantibodies; D015922:Complement C1q