Association of serum levels of galectin-9 and IP-10 with disease activation in lupus nephritis
Sibel Varelci, Suzan Cinar, Erdem Gürel, Safak Mirioglu, Omer Uludag, Ege Sinan Torun, Yasemin Yalcinkaya, Ahmet Gul, Murat Inanc, Bahar Artim-EsenObjectives
Galectin-9 and IP-10 are downstream effectors of the type I interferon (IFN) pathway and have been proposed as surrogate biomarkers of IFN signature in systemic lupus erythematosus (SLE). This study aimed to investigate the association of serum Galectin-9 and IP-10 levels with disease activity in lupus nephritis (LN) and to compare them with those in disease controls, including antiphospholipid syndrome (APS) and primary Sjögren’s disease (pSD), and healthy controls.
Methods
Fifty-nine patients with biopsy-proven LN (31 active, 28 inactive), 36 patients with APS, 17 patients with pSD, and 61 healthy volunteers were enrolled. All SLE patients fulfilled both the SLICC and the 2019 EULAR/ACR classification criteria. Serum Galectin-9 and IP-10 levels were measured by enzyme-linked immunosorbent assay (ELISA) in samples obtained at the same visit as the disease activity assessment. In patients with active LN, kidney biopsy was performed as part of the same clinical evaluation, whereas patients with inactive LN had a previously established biopsy-proven diagnosis of LN.
Results
Among 59 LN patients (74.6% female; mean age 37.9 ± 12 years), serum levels of both biomarkers were significantly higher in the active LN group compared with inactive LN, APS, pSD, and healthy controls (p ≤ 0.05). Biomarker levels did not differ significantly among the inactive LN, APS, and pSD groups (p > 0.05); however, all three groups showed significantly higher levels compared to healthy controls (p ≤ 0.05). Both biomarkers showed weak but statistically significant correlations with SLEDAI scores (Galectin-9: r = 0.36, p = 0.004; IP-10: r = 0.33, p = 0.009). ROC analysis demonstrated moderate discriminatory ability for distinguishing active from inactive LN (AUC: 0.695 for Galectin-9; 0.658 for IP-10).
Conclusion
Serum Galectin-9 and IP-10 are elevated in active LN and show weak but statistically significant correlations with SLEDAI scores. However, elevated levels are not specific to LN, as similar values are observed in inactive LN, APS, and pSD, suggesting these markers reflect a shared IFN-driven inflammatory state rather than LN-specific pathology.