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.Material and 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. Conclusion:These results suggest that IL-17A, while participating in inflammation, may also serve a protective purpose in SLE patients.

Background Insulin growth factor-1 (IGF1) activates cell proliferation pathways and inhibits apoptosis. IGF1 is involved in tumour growth and required for T-cell independent activation of B cells. Activated B cells and autoantibody production are a hallmark of systemic lupus erythematosus (SLE). To investigate the possible role of IGF1 in SLE, we studied IGF1 across clinical characteristics, immunological biomarkers, disease activity and organ damage in SLE patients. Method In a cross-sectional study, we collected clinical characteristics, medication, disease activity (SLEDAI-2K) and organ damage (SDI) for 94 SLE patients. Autoantibodies and cytokines were measured by ELISA, and levels of IGF1 and IGF binding protein 3 (IGFBP3) by chemiluminescence. Free IGF1 was estimated by the IGF1:IGFBP3 ratio. Healthy controls served as a comparator group. Results There was a significant age-related decline in IGF1, IGFBP3 and free IGF1 (IGF1:IGFBP3 ratio) that was similar in SLE patients and controls with very few outliers. Free IGF1 was inversely related to blood pressure (Rs -0.327, p < 0.01) and HbA1c (Rs -0.31, p < 0.01). Free IGF1 was higher in disease-modifying antirheumatic drug-treated patients ( p < 0.01), but there was no significant association between the IGF1 axis and autoantibody profiles, cytokine levels or SLEDAI-2K or SDI categories. IGF1 correlated inversely with BAFF level and B, natural killer and CD8 + cell counts. Conclusion Free IGF1 levels in SLE patients declined appropriately with age. IGF1 levels were not associated with disease activity, severity or autoantibody levels in SLE. Free IGF1 had positive metabolic effects in SLE and may play an indirect role in dampening the cellular immune response by downregulating B- and T-cell activity.

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