FC063: Serum and Urine Galectin-9, Ip-10 and Siglec-1 as Biomarkers of Disease Activity in Patients with Systemic Lupus Erythematosus Compared to Anca-Associated Vasculitis: A Longitudinal Study
Authors: Mirioglu Safak , Cinar Suzan , Uludag Omer , Gurel Erdem , Varelci Sibel , Ozluk Yasemin , Kilicaslan Isin , Yalcinkaya Yasemin , Yazici Halil , Gul Ahmet , Inanc Murat , Artim-Esen Bahar 
Published: May 2022

Abstract

BACKGROUND AND AIMS
Galectin-9, interferon-inducible protein-10 (IP-10) and sialoadhesin (SIGLEC-1) are considered as potential biomarkers reflecting disease activity in patients with systemic lupus erythematosus (SLE). In this study, we aimed to investigate the association of serum and urine galectin-9, IP-10 and SIGLEC-1 with disease activity in patients with SLE. Also, we compared the results with ANCA-associated vasculitis (AAV) to test the specificity of the biomarkers.

METHOD
A total of 63 patients with active SLE (31 renal and 32 extrarenal) were included in the study. A total of 30 patients with inactive SLE (15 renal and 15 extrarenal), 17 with renal active AAV and 32 healthy volunteers were selected as control groups. Serum (s) and urine (u) levels of galectin-9, IP-10 and SIGLEC-1 were tested using ELISA. Urine levels of biomarkers were normalized by urine creatinine.

RESULTS
Of 142 participants, 109 (76.7%) were female and median age was 36 (28.75–48) years. Groups were comparable with regard to sex and age distribution except for AAV. In AAV group, seven patients (41.1%) were female and median age was 60 (48–65.5) years. Proliferative lupus nephritis (LN) (class III/III + V and IV/IV + V) were found in 22 patients with active renal SLE (70.9%), while 6 patients (19.3%) had pure class V and 3 (9.7%) had class II LN. Levels of sIP-10, uIP-10, sGalectin-9 and uSIGLEC-1 were significantly higher in the active SLE group compared to the inactive SLE group (sIP-10; P = 0.046, uIP-10; P &lt; 0.001, sGalectin-9; P = 0.031 and uSIGLEC-1; P = 0.006); however, no differences were detected in the comparison of uGalectin-9 and sSIGLEC-1 between these two groups (uGalectin-9; P = 0.180 and sSIGLEC-1; P = 0.699). sIP-10 (P &lt; 0.001), uIP-10 (P = 0.029) and uGalectin-9 (P &lt; 0.001) were significantly higher in patients with active SLE compared to AAV (Table 1). Serum and urine galectin-9, IP-10 and SIGLEC-1 did not differ between patients with active renal and extrarenal SLE. Levels of sIP-10, uIP-10 and uSIGLEC-1 were correlated with SLE Disease Activity Index (SLEDAI). ROC analyses confirmed that sIP-10, uIP-10, sGalectin-9 and uSIGLEC-1 discriminated disease activity in SLE (Figure 1). Serum and urine levels of all biomarkers were retested in 41 of 63 patients (65%) with active SLE after a median treatment of 8 (5–22.5) months. At the time of the second tests, there was a significant decrease in disease activity as measured by SLEDAI [2 (0–4)] compared to the time of the first tests [10 (6–15.5)]. Comparison of sGalectin-9 levels between the sample at the time of active disease and remission showed a very significant decline (P &lt; 0.001). uGalectin-9, sIP-10 and uSIGLEC-1 also decreased after treatment; however, the difference was not statistically significant.

CONCLUSION
sIP-10, uIP-10, sGalectin-9 and uSIGLEC-1 are associated with disease activity in SLE. None is able to discriminate active renal from active extrarenal disease. sIP-10 and uIP-10 are specific for active SLE compared to renal active AAV. sGalectin-9 may be a valuable biomarker to monitor response after treatment for active disease.
Funded by Scientific Research Projects Coordination Unit of Istanbul University. Project number: TSA-2019–34 218.