An antibody-based leukocyte-capture microarray for the diagnosis of systemic lupus erythematosus

PLoS One. 2013;8(3):e58199. doi: 10.1371/journal.pone.0058199. Epub 2013 Mar 13.

Abstract

The diagnosis of Systemic Lupus Erythematosus (SLE) is challenging due to its heterogeneous clinical presentation and the lack of robust biomarkers to distinguish it from other autoimmune diseases. Further, currently used laboratory tests do not readily distinguish active and inactive disease. Several groups have attempted to apply emerging high throughput profiling technologies to diagnose and monitor SLE. Despite showing promise, many are expensive and technically challenging for routine clinical use. The goal of this work is to develop a better diagnostic and monitoring tool for SLE. We report a highly customisable antibody microarray that consists of a duplicate arrangement of 82 antibodies directed against surface antigens on peripheral blood mononuclear cells (PMBCs). This high-throughput array was used to profile SLE patients (n = 60) with varying disease activity, compared to healthy controls (n = 24), patients with rheumatoid arthritis (n = 25), and other autoimmune diseases (n = 28). We used a computational algorithm to calculate a score from the entire microarray profile and correlated it with SLE disease activity. Our results demonstrate that leukocyte-capture microarray profiles can readily distinguish active SLE patients from healthy controls (AUROC = 0.84). When combined with the standard laboratory tests (serum anti-dsDNA, complements C3 and C4), the microarrays provide significantly increased discrimination. The antibody microarrays can be enhanced by the addition of other markers for potential application to the diagnosis and stratification of SLE, paving the way for the customised and accurate diagnosis and monitoring of SLE.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antibodies / immunology*
  • Antibodies / metabolism
  • Antigens, CD / metabolism
  • Biomarkers
  • Cluster Analysis
  • Female
  • Humans
  • Leukocytes / immunology*
  • Leukocytes / metabolism
  • Lupus Erythematosus, Systemic / diagnosis*
  • Lupus Erythematosus, Systemic / metabolism
  • Male
  • Middle Aged
  • Reproducibility of Results
  • Sensitivity and Specificity
  • Tissue Array Analysis* / methods
  • Young Adult

Substances

  • Antibodies
  • Antigens, CD
  • Biomarkers

Grant support

Studies were supported by the NWG Macintosh Memorial Fund of the Department of Anatomy & Histology, University of Sydney and the Special Purposes Trust Fund and generous donors to the Department of Clinical Immunology, Royal Prince Alfred Hospital. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.