SLE-key® rule-out serologic test for excluding the diagnosis of systemic lupus erythematosus: Developing the ImmunArray iCHIP®

Abstract

We describe here the development, verification and validation of the SLE-key® rule-out test for a definitive rule-out of a diagnosis of systemic lupus erythematosus (SLE). The test uses the proprietary iCHIP® micro-array technology platform (Fattal et al., 2010) to identify discriminating patterns of circulating autoantibodies among SLE patients compared to self-declared healthy individuals. Given the challenges associated with the diagnosis of SLE and the healthcare costs of delayed diagnosis and misdiagnosis, a definitive rule-out test can provide significant clinical benefits to patients and potentially major cost savings to healthcare systems.

Molecular mimicry, genetic homology, and gene sharing proteomic “molecular fingerprints” using an EBV (Epstein-Barr virus)-derived microarray as a potential diagnostic method in autoimmune disease

“…Published data from an FDA-approved protein microarray showed that levels of IgG response to host proteins and EBV-encoded EBNA-1 protein and other viral proteins Table 4 IgG response was present to EBNA-1 protein A/T hook region GRPGAPGG (aa 51-57) 4 15 could diagnosis both SLE and scleroderma with sensitivity and specificity similar or greater to conventional ANA testing [15]. Addition of viral protein antigens in this assay significantly improved the sensitivity and specificity, although the specific IgG-binding epitopes recognized by immunoglobulin G were not disclosed [15,16]. In this work, IgG-binding results are presented derived from a proprietary laser-printed peptide microchip containing overlapping peptides from immunologically important EBV proteins to illustrate the potential of this new technology.…”

“…Presently, the standard of diagnosis for many autoimmune diseases is based on ANA (anti-nuclear antibody) assays in which immunoglobulin binding is characterized against the cell cytoplasm and nucleus and related IgG binding assays. While ANA and immunoassay technology can in principle be automated, a more recent approach is the use of specific antigenic host and viral proteins David H. Dreyfus printed in a microarray with sensitivity similar or great than that of the ANA [15,16]. Using proteomic technology, hundreds or even thousands of epitopes can be analyzed simultaneously with a single serum sample.…”

“…/T hook region of EBNA-1 AGAGGGAG(aa 103-110) also bound IgG at lower levels. Binding to the EBNA-1 A/T hook peptide GRPGAPGG is approximately 10 times greater than maximal binding to ZEBRA epitope TPDPYQV (aa[15][16][17][18][19][20][21] …”

Biomarkers in connective tissue diseases

“…The test is validated as a clinical test to exclude a diagnosis of SLE if no compelling clinical evidence exists or to support a low likelihood of SLE. 37 …”

Diagnostic and prognostic tests in systemic lupus erythematosus

“…We pursued one such application of protein profiling in SLE with the use of iCHIP microarray technology for the development, verification, and validation of a definitive serologic rule-out diagnostic test: the SLE-Key rule-out test [88]. …”