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A10.23 Stratification of SLE Patients for Improved Diagnosis and Treatment
  1. Helena Idborg1,
  2. Stefan Rännar2,
  3. Ganna Oliynyk1,
  4. Jenny Forshed3,
  5. Rui Mamede Branca3,
  6. Magdalena Donten2,
  7. Kate Bennett2,
  8. Johanna Gustafsson1,
  9. Anna Vikerfors1,
  10. Lennart Truedsson4,
  11. Bo Nilsson5,
  12. Iva Gunnarsson1,
  13. Johan Trygg2,6,
  14. Janne Lehtiö3,
  15. Torbjörn Lundstedt2,6,
  16. Elisabet Svenungsson1,
  17. Per-Johan Jakobsson1
  1. 1Rheumatology Unit, Department of Medicine, Karolinska Institutet and Karolinska University Hospital, Stockholm, Sweden
  2. 2AcureOmics AB, Umeå, Sweden
  3. 3Clinical Proteomics Mass Spectrometry, Dept. of Oncology-Pathology, Science for Life Laboratory and Karolinska Institutet, Stockholm, Sweden
  4. 4Section of Microbiology, Immunology and Glycobiology, Department of Laboratory Medicine, Lund University, Lund, Sweden
  5. 5Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden
  6. 6Computational Life Science Cluster, Department of Chemistry, Umeå University, Umeå, Sweden
  7. 7Organic Pharmaceutical Chemistry BMC, Uppsala University, Uppsala, Sweden

Abstract

Background Systemic autoimmune diseases (SAIDs) affect about 2% of the population in Western countries. Sufficient diagnostic criteria are lacking due to the heterogeneity within diagnostic categories and apparent overlap regarding symptoms and patterns of autoantibodies between different diagnoses. Systemic lupus erythematosus (SLE) is regarded as a prototype for SAIDs and we hypothesise that subgroups of patients with SLE may have different pathogenesis and should consequently be subject to different treatment strategies.

Objectives Our goal is to find new biomarkers to be used for the identification of more homogenous patient populations for clinical trials and to identify sub-groups of patients with high risk of for example cardiovascular events.

Methods In this study we have utilised 320 SLE patients from the Karolinska lupus cohort and 320 age and gender matched controls. The SLE cohort was characterised based on clinical, genetic and serological data and combined by multivariate data analysis in a systems biology approach to study possible subgroups. A pilot study was designed to verify and investigate suggested subgroups of SLE. Two main subgroups were defined: One group was defined as having SSA and SSB antibodies and a negative lupus anticoagulant test (LAC), i.e., a “Sjögren-like” group. The other group was defined as being negative for SSA and SSB antibodies but positive in the LAC test.i.e. an “APS-like” group. EDTA-plasma from selected patients in these two groups and controls were analysed using a mass spectrometry (MS) based proteomic and metabolomic approach. Pathway analysis was then performed on the obtained data.

Results Our pilot study showed that differences in levels of proteins and metabolites could separate disease groups from population controls. The profile/pattern of involved factors in the complement system supported a division of SLE in two major subgroups, although each individual factor was not significantly different between subgroups. Complement factor 2 (C2) and membrane attack complex (MAC) were analysed in the entire cohort with complementary methods and C2 verifies our results while the levels of MAC did not differ between SLE subgroups. The generated metabolomics data clearly separated SLE patients from controls in both gas chromatography (GC)-MS and liquid chromatography (LC)-MS data. We found for example that tryptophan was lower in the SLE patients compared to controls.

Conclusions Our systems biology approach may lead to a better understanding of the disease and its pathogenesis, and assigning patients into subgroups will result in improved diagnosis and better outcome measures of SLE.

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