Immune complex signatures of patients with active and inactive SLE revealed by multiplex protein binding analysis on antigen microarrays

PLoS One. 2012;7(9):e44824. doi: 10.1371/journal.pone.0044824. Epub 2012 Sep 11.

Abstract

Systemic lupus erythematosus is characterized by dysfunctional clearance of apoptotic debris and the development of pathogenic autoantibodies. While the complement system is also involved in the disease no attempt has been made to generate a comprehensive view of immune complex formation from various autoantigens. We increased the complexity of autoantibody profiles by measuring the binding of two complement proteins, C3 and C4, in addition to two antibody classes, IgG and IgM, to a collection of autoantigens. These complement components covalently bind to those microarray features where antibodies and other serum components induce complement activation. Using this technology, we compared functional serum antibody profiles of control subjects (n = 31) and patients with lupus erythematosus (n = 61) in the active (n = 22) and inactive (n = 39) phase of the disease. Multivariate analysis was applied to identify contributions of binding data on 25 antigens to the discrimination of the study groups. Receiver operating characteristic analysis was used to portray the discriminative property of each measured parameter for each antigen in pairwise group comparisons. Complement C3 and C4 deposition increased on autoantibody targets in spite of the decreased serum complement concentrations, and decreased on other autoantigens, demonstrating the imbalance of complement function in patients with lupus erythematosus. Our observations confirmed previously known markers of disease and showed that C3 and C4 deposition data were at least as powerful as Ig binding data in separating the study groups.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Antigen-Antibody Complex / immunology
  • Antigens / chemistry*
  • Autoantibodies / immunology
  • Autoantigens / chemistry
  • Complement Activation
  • Complement System Proteins
  • Female
  • Humans
  • Immunoglobulin G / chemistry
  • Immunoglobulin M / chemistry
  • Lupus Erythematosus, Systemic / blood*
  • Lupus Erythematosus, Systemic / immunology*
  • Male
  • Middle Aged
  • Multivariate Analysis
  • Protein Array Analysis / methods*
  • ROC Curve

Substances

  • Antigen-Antibody Complex
  • Antigens
  • Autoantibodies
  • Autoantigens
  • Immunoglobulin G
  • Immunoglobulin M
  • Complement System Proteins

Grant support

This work was supported by grant KMOP-1.1.1-08/1-2008-0028 from National Development Agency to Diagnosticum. The European Union and the European Social Fund have provided financial support to the project under the grant agreement no. TÁMOP 4.2.1./B-09/1/KMR-2010-0003. K.P is supported by the János Bolyai Research Scholarship of the Hungarian Academy of Sciences. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.