Background/Purpose:

Sub-classification of Lupus Erythematosus (LE) patients is largely based on defined clinical criteria while biological factors associating with or contributing to these clinical features are less defined. Further elucidation of molecular events present in distinct clinical subsets of LE patients may aid in the identification of subjects more responsive to existing therapeutics, disease-classifying biomarkers and new therapeutic targets. To that end, cross-sectional studies were undertaken with SLE subjects having active skin involvement and subjects with Discoid Lupus Erythematosus (DLE) or Subacute Cutaneous LE (SCLE) to determine if LE patient subsets with skin manifestations can be molecularly distinguished. 

Methods:

A prospective multicenter cross-sectional biomarker study (NOCOMPOUNDLUN0001) was undertaken with LE patients having SLE, SCLE or DLE, all with active cutaneous involvement at time of sample collection. A second single center independent study also occurred to procure SLE, SCLE, DLE and healthy volunteer (HV) samples. In total, samples from 6 SLE, 21 SCLE, 19 DLE and 10 HV were collected under informed consent. Serum collected from these donors was extensively profiled for autoantibody specificities and cytokines using ProtoArray® and DiscoveryMAP® v 3.3 systems, respectively. In addition, RNA was extracted from skin biopsy collections at lesional and/or non-lesional sites from individual subjects or from HV donors and gene expression quantified using Affymetrix arrays.  All data was further analyzed using “R” software. Topological networks were created using Ayasdi. 

Results:

Serum samples from DLE, SCLE, SLE and HV subjects were extensively profiled for autoantibody specificities and soluble cytokines. Protein array chips containing more than 9,000 protein features were utilized to determine if unique autoantibody specificity profiles associate with LE patient sub classifications. Antibodies against 84 distinct proteins were significantly elevated in the sera of LE versus HV subjects. 55, 10, and 16 of these were uniquely enriched in DLE, SCLE and SLE subsets, respectively. Cytokine profiling was also performed using a bead-based panel containing over 300 analytes. 75 cytokines were significantly elevated in the sera of LE versus HV subjects. Of these, 5, 33, and 5 were uniquely enriched in DLE, SCLE and SLE patient subsets, respectively. 15 cytokines were elevated across DLE, SCLE and SLE subjects versus HV. Gene expression data from skin also demonstrated unique gene signatures for each LE subset. Topological networks from this data set corroborated these findings and indicate that unique proteomic and gene expression profiles associate with specific LE patient subsets.

Conclusion:

In the LE cohorts examined, serum autoantibody and cytokine profiles were identified that distinguished subsets of cutaneous patients or were commonly elevated across SLE, DLE and SCLE subjects. These findings correlated with the identification of SLE, DLE and SCLE specific molecular pathways in skin found by gene expression array. Further studies with more subjects are required to further validate these findings.

« Back to 2015 ACR/ARHP Annual Meeting

ACR Meeting Abstracts - https://acrabstracts.org/abstract/identification-of-molecular-biomarkers-to-distinguish-systemic-lupus-erythematosus-with-skin-involvement-from-discoid-lupus-erythematosus-and-subacute-cutaneous-erythematosus-provisional-results-from/