Determinants of the complement-fixing ability of recipient presensitization against HLA antigens

Transplantation. 2007 Mar 27;83(6):727-33. doi: 10.1097/


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Antigen-Antibody Complex / immunology*
  • Complement Activation / physiology
  • Complement Fixation Tests / methods
  • Complement System Proteins / immunology
  • Complement System Proteins / physiology*
  • Female
  • Graft Rejection / immunology
  • HLA Antigens / immunology*
  • Humans
  • Immunoglobulin G / immunology
  • Immunoglobulin M / immunology
  • Isoantibodies / immunology*
  • Kidney Transplantation / immunology*
  • Male
  • Middle Aged
  • Risk Factors


  • Antigen-Antibody Complex
  • HLA Antigens
  • Immunoglobulin G
  • Immunoglobulin M
  • Isoantibodies
  • Complement System Proteins