Abstract
BackgroundPatients with SLE display marked clinical and immunlogical heterogeneity. The purpose of the study was to investigate patterns of serum cytokines in patients with active and stable systemic lupus erythematosus (SLE) and to determine how they relate to clinical phenotype.MethodsSerum levels of 10 cytokines were measured retrospectively in a cohort of patients with SLE and in healthy controls using a high-sensitivity multiplex bead array. Disease activity was determined using the Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) and British Isles Lupus Assessment Group (BILAG-2004) indices. Logistic regression models were used to determine the association between cytokine levels and active SLE. Principal component analysis (PCA) and cluster analysis was then used to identify subgroups of patients on the basis of cytokine levels.ResultsSerum chemokine (C-X-C motif) ligand 10 (CXCL10) and CXCL13 were significantly higher in patients with SLE compared to healthy controls. Two cytokines (pentraxin-related protein (PTX3) and CXCL10) were significantly higher in patients with active disease after adjustment for potential confounding factors. Measurement of four cytokines (CXCL10, IL-10, IL-21 and PTX3) significantly improved the performance of a model to identify patients with clinically active disease. Cluster analysis revealed that the patients formed 3 distinct groups, characterised by higher levels of interferon alpha (IFNα) and B lymphocyte stimulator (BLyS) (group 1), increased CXCL10 and CXCL13 (group 2) or low levels of cytokines (group 3). Group 2 had significantly lower serum complement and higher anti-double-stranded DNA antibodies and increased prevalence of inflammatory arthritis.ConclusionsMultiplex analysis has identified a serum cytokine signature for active SLE. Within the SLE population distinct cytokine subgroups were identified, with differing clinical and immunological phenotypes that appeared stable over time. Assessment of cytokine profiles may reveal unique insights into disease heterogeneity.
Highlights
Patients with systemic lupus erythematosus (SLE) display marked clinical and immunlogical heterogeneity
Patients with SLE are reported to have increased levels of many cytokines including interleukin (IL)-10, IL-17 and interferon alpha (IFNα) these are often measured in isolation making it difficult to understand how cytokine networks exist in SLE [7]
We aimed to determine how these cytokines related to disease activity and to determine whether individual cytokines or groups of cytokines were associated with specific SLE disease features
Summary
Patients with SLE display marked clinical and immunlogical heterogeneity. The purpose of the study was to investigate patterns of serum cytokines in patients with active and stable systemic lupus erythematosus (SLE) and to determine how they relate to clinical phenotype. Systemic lupus erythematosus (SLE) is a systemic inflammatory autoimmune disease with a broad clinical and immunological phenotype, and marked variability in response to treatment. A number of studies have identified autoantibody clusters in SLE, again reflecting the immunopathological heterogeneity within this patient group [3, 4]. Cytokine levels may be Reynolds et al Arthritis Research & Therapy (2018) 20:173 influenced by a number of endogenous and exogenous factors including clinical disease activity, circadian variation, the presence of infection and immunosuppressant treatment [6]. Patients with SLE are reported to have increased levels of many cytokines including interleukin (IL)-10, IL-17 and interferon alpha (IFNα) these are often measured in isolation making it difficult to understand how cytokine networks exist in SLE [7]
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
