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AB0078 Identification of Novel Candidate Biomarkers for Systemic Lupus Erythematosus Patient Characterization
  1. V. Sippel1,
  2. H. Farine1,
  3. D. Omlin2,
  4. P.M. Groenen1,
  5. D.S. Strasser1
  1. 1Translational science
  2. 2Knowledge Center, Actelion Ltd, Allschwil, Switzerland

Abstract

Background Systemic Lupus Erythematosus (SLE) is an autoimmune disease with heterogeneous clinical manifestations. Beside clinical criteria, diagnosis of SLE patients entails immunological factors such as circulating auto-antibodies and complement factors1.

Accurate diagnosis of SLE remains a challenge and patient heterogeneity is likely the reason why in the last 50 years only 1 drug was approved2. Therefore additional biomarkers are needed to characterize patients and disease-driving pathways. As an example IP-10 has emerged as a biomarker for disease activity and flaring, representing IFNg and TNFa pathway actvity3,4.

Objectives The identification of candidate biomarkers for SLE patient characterization using plasma samples from commercial biorepositories.

Methods Plasma samples from 20 SLE patients and 20 age-, gender- and ethnicity-matched healthy subjects were acquired from three different commercial biorepositories each. IP-10 was used to identify the optimal sample set showing homogenous healthy subjects well separated from SLE patients. The chosen sample set was screened with a 30-plex immunoassay focused on pro-inflammatory cytokines and chemokines. Biomarkers showing a statistically significant difference between healthy and disease underwent a comprehensive knowledge databases search to investigate the novelty. Candidate SLE disease biomarkers were further characterized by spearman correlation, Receiver Operating Characteristic (ROC) and Principle Component Analysis (PCA).

Results In two sample sets significantly higher IP-10 levels were confirmed in SLE patients which correlated with the disease activity available from one biorepository. We identified 14 statistically significant increased biomarkers in SLE patients (p<0.0001) with areas under the ROC curve between 0.856 and 0.975. Literature database search allowed to categorize biomarkers either as well-known in the SLE world as TNFa or relatively novel as Eotaxon-1. Additional novel biomarkers were TARC, IL-16, IL-7 and MIP-1b. Principle Component (PC) 1 described 36% of the data and separated the healthy subjects from SLE patients. The novel biomarkers grouped with TNFa on PC1, but described 4 separate clusters on PC2 (15%).

Conclusions Several relatively novel candidate biomarkers were identified and multivariate analysis revealed a potential use for patient stratification. Confirmation of those biomarkers in larger SLE cohorts with detailed clinical characteristics is needed.

References

  1. Boyce EG. Belimumab: review of use in systemic lupus erythematosus. Clin Ther 2012 February.

  2. Petri M, et al. Derivation and Validation of Systemic Lupus International Collaborating Clinics Classification Criteria for Systemic Lupus Erythematosus. Arthritis Rheum 2012 August.

  3. Kong KO, et al. Enhanced expression of interferon-inducible protein-10 correlates with disease activity and clinical manifestations in systemic lupus erythematosus. Clin Exp Immunol 2009 April.

  4. Bauer JW, et al. Interferon-regulated chemokines as biomarkers of systemic lupus erythematosus disease activity: a validation study. Arthritis Rheum 2009 October.

Disclosure of Interest None declared

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