Mariele Gatto

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.

Objective To investigate potential associations between B cell–related immunologic changes and development of inflammatory arthritis (IA) after treatment with immune checkpoint inhibitors (ICIs). Methods Patients who developed ICI‐induced IA (ICI‐IA) and patients who did not develop immune‐related adverse events (non‐IRAE) after receiving ICIs to treat metastatic melanoma were consecutively recruited. Blood samples were collected at the time of ICI‐IA occurrence and at different time points during treatment. Peripheral blood B cell subsets during ICI treatment were analyzed by flow cytometry. Rheumatoid factor, anti–citrullinated protein antibodies, and antibodies against joint‐related proteins were measured. Results Proportions of CD19+ B cells were higher in patients with ICI‐IA (n = 7) compared to patients with non‐IRAE (n = 15) (median 11.7% [interquartile range (IQR) 9.7–16.2%] versus 8.1% [IQR 5.7–11.0%]; P = 0.03). The proportion and absolute numbers of transitional CD19+CD10+CD24 high CD38 high B cells were increased in patients with ICI‐IA compared to non‐IRAE patients (median 8.1% [IQR 4.9–12.1%] versus 3.6% [IQR 1.9–4.9%]; median 10.7 cells/μl [IQR 8.9–19.6] versus 4.4 cells/μl [IQR 2.3–6.6]; P < 0.01 for both). In addition, higher levels of transitional B cells were associated with development of ICI‐IA (odds ratio 2.25 [95% confidence interval 1.03–4.9], P = 0.04). Transitional B cells increased before the onset of overt ICI‐IA and decreased between the active and quiescent stages of ICI‐IA ( P = 0.02). Autoantibodies to type II collagen epitopes were detected in up to 43% of ICI‐IA patients compared to none of the non‐IRAE patients ( P = 0.02). Conclusion Development of ICI‐IA is accompanied by an increase in transitional B cells and by production of autoantibodies to joint‐related proteins. Monitoring of B cell–driven abnormalities upon ICI treatment may help earlier recognition of ICI‐IA. image