title: IL-17A levels in systemic lupus erythematosus associated with inflammatory markers and lower rates of malignancy and heart damage: Evidence for a dual role.
abstract: OBJECTIVE
  The interleukin 17 (IL-17) cytokine family is involved in a number of chronic inflammatory diseases. In spite of contradictory findings and a lack of causality in clinical studies, IL-17 inhibition for systemic lupus erythematosus (SLE) has regained attention as a potential therapeutic pathway, after demonstrating disease-modifying capabilities in ankylosing spondylitis. We investigated the clinical associations of interleukin 17 A (IL-17A) in patients with SLE.
  
  
  METHODS
  A cross-sectional study was performed involving SLE patients (n=102; age: 49 years; 86% female) recruited from a regional registry. IL-17A levels were determined by immunoassay, disease activity by Systemic Lupus Erythematosus Disease Activity Index-2K (SLEDAI-2K), and cumulative damage by Systemic Lupus International Collaborative Clinics Damage Index (SDI) scores. Non-parametric techniques were used to examine the association between IL-17A and disease activity and autoantibody profiles were compared with healthy controls (n=31): principal component analysis (PCA) was used to determine the interplay of immune cells across disease states and damage development in SLE patients.
  
  
  RESULTS
  SLE patients had higher IgG levels, lower T-cell and B-cell counts, but median IL-17A levels did not differ from the controls (28.4 vs. 28.4 pg/mL, p=0.9). In SLE patients, IL-17A did not correlate with SLEDAI-2K or SDI, but was inversely related with age (correlation coefficients, Rs.=-0.29, p<0.05), systolic blood pressure (Rs.=-0.31, p<0.05), years of smoking (Rs.=-0.43, p<0.05), cumulative heart (Rs.=-0.22, p<0.05), and malignancy damage (Rs.=-0.18, p<0.05). Serological correlations for IL-17A existed with immunoglobulin G (IgG) levels (Rs.=0.21, p<0.05), high sensitivity C-reactive protein (hs-CRP) levels (Rs.=0.28, p<0.05), proteinuria (Rs.=0.64, p<0.05), and pre-albumin (Rs.=-0.22, p<0.05). Longitudinal data showed only modest fluctuation in IL-17A levels, independent of SLEDAI-2K.
  
  
  CONCLUSIONS
  These results suggest that IL-17A, while participating in inflammation, may also serve a protective purpose in SLE patients.
authors.affiliation: Rheumatology Group, The University of Western Australia School of Medicine, Crawley, Western Australia.
authors.forename: Warren
authors.initials: W
authors.lastname: Raymond
authors.affiliation: Department of Clinical Medicine, Bone & Joint Group, Arctic University, Tromsø, Norway.
authors.forename: Gro
authors.initials: G
authors.lastname: Ostli-Eilertsen
authors.affiliation: Rheumatology Group, The University of Western Australia School of Medicine, Crawley, Western Australia.
authors.forename: Sheynae
authors.initials: S
authors.lastname: Griffiths
authors.affiliation: Rheumatology Group, The University of Western Australia School of Medicine, Crawley, Western Australia; Department of Clinical Medicine, Bone & Joint Group, Arctic University, Tromsø, Norway; Department of Rheumatology, Sir Charles Gairdner Hospital, Nedlands, Western Australia.
authors.forename: Johannes
authors.initials: J
authors.lastname: Nossent
keywords: IL-17A; SLEDAI; Systemic Lupus Erythematosus; organ damage