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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.