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Table 1 Potential biomarkers and their proposed applications in SLE

From: Unmet medical needs in systemic lupus erythematosus

Category Biomarker Associations Comments
Susceptibility IRF-5   
  STAT-4 HLA-DRB1 Specific haplotypes confer increased susceptibility to SLE. Genome-wide association studies have identified many loci, mostly related to immune Genetic epistasis between different loci has been described
  PTPN22 regulatory genes  
  Fcγ receptors   
  Complement proteins Deficiency in early components of the classical complement pathway is a strong risk factor for SLE Partial C4 deficiency due to gene copy number variations increases the risk of SLE
Disease activity IFNα High levels of IFNα or IFN inducible genes Despite the association with activity, the
   (IFN signature) and chemokines correlated with disease activity IFN signature was not predictive of flare in longitudinal studies
  B-cell subsets CD27high plasma cells correlated with disease activity  
  Serum cytokines, receptors and adhesion molecules Multiple cytokines (for example, IL-6, IL-10, IL-16, IL-18), soluble receptors (sIL-2 R) and adhesion molecules (for example, sICAM and sVCAM) have been suggested to correlate with disease activity Data are limited and almost all proposed candidates are still far from being established as a reliable marker in SLE
Disease severity IFNα High IFN signature group has more severe disease manifestations Holds the potential to identify high-risk patients
Disease subtype IFNα High versus low IFN groups have distinct clinical features, autoantibody associations and genetic profiles IFN signature and BLyS levels may potentially define subgroups of patients
  BLyS High BLyS levels are associated with specific autoantibodies  
Flares BLyS Higher and rising BLyS levels were predictive of increase in disease activity at subsequent visit The association has not been consistent across the studies
Organ specific Anti-C1-q antibodies Correlate with the presence and severity of lupus nephritis Potential robust marker for lupus nephritis
  Anti-NR2 antibodies Associated with neuropsychiatric manifestations in a murine model Human results have been largely negative
  1. Anti NR2 antibodies, anti-N-methyl-D-asparate (NMDA) receptor antibodies; BLyS, B-lymphocyte stimulator; HLA, human leukocyte antigen; IFN, interferon; IRF, interferon regulatory factor; PTPN22, protein tyrosine phosphatase N22; sICAM, soluble intracellular adhesion molecule; SLE, systemic lupus erythematosus; STAT, signal transduction and activator of transcription; sVCAM, soluble vascular adhesion molecule.