Background/Purpose:

Elevated levels of sTREM-1 have been previously found in patients with SLE. A prospective, case-control, longitudinal study aimed to assess the value of urinary and plasma levels of sTREM-1 in evaluating disease activity in patients with active renal and non-renal SLE.

Methods:

15 patients with active renal lupus (ARL), 15 patients with active non-renal lupus (ANRL), and 30 patients with inactive lupus (IL), defined by baseline score of Safety of Estrogen in Lupus National Assessment-Systemic Lupus Erythematosus Disease Activity Index (SELENA-SLEDAI) ≥ or < 6 and renal-SLEDAI ≥ 4 or 0. Urine and plasma samples were collected and kept at -70°c until assayed for sTREM-1 levels using commercial ELISA. Urinary values were normalized for creatinine (Cr.) excretion. Plasma and urine samples of healthy individuals served as healthy control (HC).

Results:

Compared to HC (urine: n=13; plasma: n =72), baseline mean urine sTREM-1 level (UsTREM-1) was significantly higher in ARL (62.38±85.14pg/mg Cr. vs. 3.05±7.19 pg/mg Cr., p=0.0015) but not in ANRL, whereas plasma sTREM-1 (PsTREM-1) was significantly higher in patients with ANRL (361.47±187.79pg/ml, 312.15pg/ml vs. 228.76±85.23pg/ml, p=0.009) and not in the ARL group. Moreover, UsTREM-1 level significantly discriminated between ALN and ANRL or IL (p=0.0056) as well as the ratio of urine-to-plasma sTREM-1 (p=0.0083), whereas PsTREM-1 was significantly higher in ANRL compared to ARL or IL (p=0.014). Baseline SELENA-SLEDAI score correlated with UsTREM-1 (p=0.0005) and PsTREM-1 (p=0.006) while renal-SLEDAI correlated only with UsTREM-1 (p=0.013). Elevated UsTREM-1 level positively correlated with higher ESR (r=0.35, p=0.03), serum anti-dsDNA antibody titer (r=0.39, p=0.006), SELENA-SLEDAI and renal-SLEDAI scores (r=0.48, p=0.0005 and r=0.36, p=0.013, respectively) and inversely correlated with lower serum C3 level (r=-0.39, p=0.005). Elevated PsTREM-1 level positively correlated with age (r=0.25, p=0.005), serum creatinine (r=0.33, p=0.0006), higher ESR (r=0.4, p=0.007), serum anti-dsDNA antibody (r=0.59, p<0.0001) and SELENA-SLEDAI score (r=0.38, p=0.006) but not with renal-SLEDAI score and serum C3 and C4 levels. Receiver operating characteristic (ROC) curves analysis of the area under the curve (AUC) displays that PsTREM-1 level differentiates between overall active SLE and IL: AUC = 0.74, 95%CI 1.001 – 1.010, p=0.01.

Conclusion:

Our data suggest that UsTREM-1 level correlates with ARL while elevated PsTREM-1 correlates with ANRL. Urine and plasma sTREM-1 might be clinically used as a biomarker for the assessment of renal and non-renal disease activity in SLE. We suggest that renal innate immune activation and particularly TREM-1 play a role in the pathogenesis of lupus nephritis.

ACR Meeting Abstracts - https://acrabstracts.org/abstract/urine-and-plasma-soluble-triggering-receptor-expressed-on-myeloid-cells-1-strem-1-differentially-correlates-with-renal-and-non-renal-systemic-lupus-erythematosus-sle-a-prospective-case-control-s/