Characterization of Serum Cytokine Profiles of Patients with Active Lupus Nephritis

Abstract

Cytokines contribute to the pathogenesis of lupus nephritis (LN), yet their value as prognostic biomarkers is still debated. We aimed to describe the serum cytokines’ profiles and prospectively assess correlations with disease features and renal response in a multicentric cohort of consecutive adult patients with biopsy-proven active LN. Cytokine associations with clinical and serological data were performed at LN diagnosis (T0), and at 3 (T3) and 6 months (T6) of follow up. Renal response according to EULAR definition was assessed at T3, T6 and T12. BAFF and interleukin (IL)-37 were measured by ELISA; IL-2, IL-10, IL-17A and IL-18 by a bead-based multiplex cytokine assay (Luminex). Thirty-nine patients with active LN (age 40.5 ± 15.6 years; F 71.8%; 84.6% proliferative LN) were enrolled, of whom twenty-nine displayed complete longitudinal records. At T0, we observed higher levels of IL-37 and IL-17 in proliferative vs. non-proliferative LN (IL-37: 0.0510 (0.0110–0.2300) vs. 0.0000 (0.0000–0.0397) ng/mL, p = 0.0441; IL-17: 2.0920 (0.5125–17.9400) vs. 0.0000 (0.0000–0.6025) pg/mL, p = 0.0026, respectively), and positive correlations between IL-10 and 24 h proteinuria (r = 0.416, p = 0.0249) and anti-dsDNA levels (r = 0.639, p = 0.0003). BAFF was higher in patients with low complement (p < 0.0001). We observed a sustained correlation between BAFF and IL-10 throughout T6 (r = 0.654, p = 0.0210). Higher baseline IL-37 and BAFF levels were associated with renal response at T3 and T6, respectively, while baseline IL-18 levels were higher in patients achieving response at T12. Our study highlights the complexity of the cytokine network and its potential value as a marker of active LN and renal response.

Lupus Nephritis Biomarkers: A Critical Review

“…Furthermore, distinct cytokines predominate in different types of LN. For example, in proliferative LN (class III/IV), the deposition of ICs beneath the endothelium leads to mesangial cell proliferation, an increase in extracellular matrix production, and the release of a remarkable array of pro-inflammatory cytokines, such as type I IFN, interleukin (IL)-1β, IL6, IL8, IL-37, and IL-17A [55]. Conversely, membranous LN (class V) is characterized by the subepithelial localization of ICs, resulting in increased complement activation and reduced inflammatory responses [55].…”

“…For example, in proliferative LN (class III/IV), the deposition of ICs beneath the endothelium leads to mesangial cell proliferation, an increase in extracellular matrix production, and the release of a remarkable array of pro-inflammatory cytokines, such as type I IFN, interleukin (IL)-1β, IL6, IL8, IL-37, and IL-17A [55]. Conversely, membranous LN (class V) is characterized by the subepithelial localization of ICs, resulting in increased complement activation and reduced inflammatory responses [55]. Levels of cytokines may prove useful in distinguishing between proliferative and non-proliferative forms of LN, and this information may be useful in guiding precise treatment and management strategies and may eliminate the need for invasive LN biopsy [55].…”

“…Conversely, membranous LN (class V) is characterized by the subepithelial localization of ICs, resulting in increased complement activation and reduced inflammatory responses [55]. Levels of cytokines may prove useful in distinguishing between proliferative and non-proliferative forms of LN, and this information may be useful in guiding precise treatment and management strategies and may eliminate the need for invasive LN biopsy [55]. Several cytokines have been examined as potential biomarkers to assess the activity, severity, and renal involvement of SLE.…”