Background/Purpose: Toll-like receptor 7 (TLR7) can sense single-stranded RNA with subsequent induction of different interferon (IFN) types including IFN lambda (IFNL) and may contribute to the development of autoimmune diseases. The present work was designed to investigate the potential role of TLR7 and IFNL1 in systemic lupus erythematosus (SLE) and their relation to disease activity and development of lupus nephritis (LN).

Methods: Thirty patients with SLE (15 patients without LN and 15 patients with LN) and 15 healthy subjects were enrolled in the study. Disease activity was assessed using the SLE disease activity index (SLEDAI). Antinuclear antibody (ANA) and anti-double stranded DNA antibodies (anti-dsDNA) titer were assayed. TLR7 expression on peripheral blood CD14+ monocytes was studied by color flow cytometry and the absolute number of CD14+ TLR7+ cells was calculated. Quantification of IFNL1 levels in serum was determined using enzyme-linked immunosorbant assay. Renal function was assessed by estimating serum creatinine, estimated glomerular filtration rate (eGFR) and urinary albumin to creatinine (UAC) ratio. Erythrocyte sedimentation rate (ESR), serum high-sensitivity C-reactive protein (hsCRP) and serum complement 3 and 4 (C3 and C4 respectively) were quantified. Renal biopsy was performed to patients with LN and classified according to the international society of nephrology/renal pathology society.

Results: The number of peripheral blood CD14+ TLR7+ monocytes and serum IFNL1 levels showed significant increases in patients with and without LN compared with healthy controls and in patients with LN compared with those without LN (P < 0.001). Changes in TLR7 expression and IFNL1 production in peripheral blood were positively correlated (P < 0.001) and both showed positive correlations with SLEDAI score, ANA and anti-dsDNA titers, serum creatinine, UAC ratio, ESR, serum hsCRP levels and renal activity index and inverse correlations with eGFR and serum C3 and C4 levels in SLE patients (P < 0.05). By plotting receiver operating characteristics (ROC) curve, the sensitivity and specificity of the number of peripheral blood CD14+ TLR7+ monocytes in discriminating SLE patients with and without LN were higher than those of serum IFNL1 levels (100% and 93.33% respectively, area under the curve (AUC) = 0.996 vs. 86.7% and 40% respectively, AUC = 0.687).

Conclusion: Activation of TLR7/IFNL1 pathway may play an important role in the pathogenesis of SLE in relation to disease activity and development of LN and could be a potential therapeutic target for the treatment of SLE and LN.

« Back to 2019 ACR/ARP Annual Meeting

ACR Meeting Abstracts - https://acrabstracts.org/abstract/peripheral-blood-toll-like-receptor-7-expression-and-serum-interferon-lambda-1-levels-in-systemic-lupus-erythematosus-and-their-relation-to-disease-activity-and-lupus-nephritis/