title: Determinants of the complement-fixing ability of recipient presensitization against HLA antigens.
abstract: BACKGROUND
  The presence of preformed alloantibodies with the ability to activate complement may pose a particular risk for kidney allograft rejection. The aim of this study was to evaluate variables that determine the complement-fixing capability of human leukocyte antigen (HLA) sensitization.
  
  
  METHODS
  Sixty-five sensitized patients with > or =10% pretransplant panel-reactive antibody (PRA) levels uncovered by immunoglobulin G [IgG]FlowPRA HLA class I and/or class II screening were included. Applying modified FlowPRA screening, sera were evaluated for patterns of alloreactive IgG subclasses and IgM, and, in parallel, for their complement-activating ability assessed by flow cytometric detection of human complement split product deposition ([C4d]FlowPRA).
  
  
  RESULTS
  Approximately two-thirds (68%) of tested sera were found to contain complement-fixing alloreactivity (> or =10%[C4d]FlowPRA). IgG1 type panel reactivity was predominant (detectable HLA class I and II reactivity in 93% and 91% of IgG-positive sera), followed by IgG3 (49%/44%), IgG2 (44%/27%), and IgG4 (19%/11%). Applying partial correlation we found an independent correlation of both %[IgG1]FlowPRA and %[IgG3]FlowPRA with %[C4d]FlowPRA reactivities (P< or =0.01). In addition, for IgG1 a contribution of the amount of bound alloantibody to complement-fixation was observed. Complement-fixation was also favored by the simultaneous presence of alloreactive IgG1, IgG3, and IgM. Previous grafting, but not pregnancy and transfusion, was independently associated with complement-fixing sensitization (P<0.05), presumably due to increased IgG1 type reactivity.
  
  
  CONCLUSIONS
  Anti-HLA antibody-triggered complement activation is dependent on both the pattern of Ig reactivities and the amount of bound antibody. Previous transplantation represents a major risk factor for the development of complement-fixing sensitization.
authors.affiliation: Department of Medicine III, Medical University of Vienna, Vienna, Austria.
authors.forename: Gregor
authors.initials: G
authors.lastname: Bartel
authors.forename: Markus
authors.initials: M
authors.lastname: Wahrmann
authors.forename: Markus
authors.initials: M
authors.lastname: Exner
authors.forename: Heinz
authors.initials: H
authors.lastname: Regele
authors.forename: Martin
authors.initials: M
authors.lastname: Schillinger
authors.forename: Walter H
authors.initials: WH
authors.lastname: Hörl
authors.forename: Georg A
authors.initials: GA
authors.lastname: Böhmig
mesh_terms: D000328:Adult; D000936:Antigen-Antibody Complex / Q000276:immunology*; D003167:Complement Activation / Q000502:physiology; D003168:Complement Fixation Tests / Q000379:methods; D003165:Complement System Proteins / Q000276:immunology / Q000502:physiology*; D005260:Female; D006084:Graft Rejection / Q000276:immunology; D006680:HLA Antigens / Q000276:immunology*; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology; D007075:Immunoglobulin M / Q000276:immunology; D007518:Isoantibodies / Q000276:immunology*; D016030:Kidney Transplantation / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D012307:Risk Factors
chemical_list: D000936:Antigen-Antibody Complex; D006680:HLA Antigens; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D007518:Isoantibodies; D003165:Complement System Proteins