IL-17A levels in systemic lupus erythematosus associated with inflammatory markers and lower rates of malignancy and heart damage: Evidence for a dual role

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.