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Human leukocyte antigen antibodies and human complement activation: role of IgG subclass, specificity, and cytotoxic

Fumiki Kushihata1, Jota Watanabe, Arend Mulder

  • 1Department of Pathology, University of Florida College of Medicine, Gainesville, FL 32608, USA.

Transplantation
|October 14, 2004
PubMed

Insights

Complement activation by human leukocyte antigen (HLA) antibodies is not well predicted by IgG binding or complement-dependent cytotoxicity (CDC) tests. Antibody specificity and target cell interactions are key factors in complement activation.

Area of Science:

  • Immunology
  • Transplantation immunology
  • Complement system

Background:

  • Human leukocyte antigen (HLA) antibodies are typically assessed for complement (C) fixation and clinical relevance using the complement-dependent cytotoxicity (CDC) test.
  • However, the sub-lytic activation of individual C components holds significant biological importance.
  • The specific requirements for HLA antibodies to activate human complement remain largely unknown.

Purpose of the Study:

  • To investigate the requirements of HLA antibodies for activating human complement.
  • To evaluate the predictive value of IgG binding and complement-dependent cytotoxicity (CDC) for complement activation by HLA antibodies.

Main Methods:

  • Flow cytometry was used to assess IgG, IgM, IgG subclasses, and human C3b deposition on T cells.
  • Sera from HLA-sensitized patients and human monoclonal HLA antibodies were utilized in comparative studies.

Main Results:

  • A poor correlation was observed between IgG amount on target cells and CDC production.
  • Human C3b deposition was more dependent on the specific serum/cell combination than IgG amount.
  • Human monoclonal HLA antibodies, primarily IgG1, showed inefficient C activation despite high IgG binding; however, combinations of two antibodies to different epitopes enhanced C3b deposition.

Conclusions:

  • Complement-dependent cytotoxicity (CDC), IgG binding, and IgG subclass are unreliable predictors of human complement activation by HLA antibodies.
  • The efficiency of complement activation is influenced by the mix of antibody specificities and target cell antigens.
  • Measuring both antibody and C3b deposition may enhance the assessment of donor-recipient compatibility in transplantation.
Abstract

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