Background and purpose This study evaluates the quantitative measurability of glial fibrillary acidic protein (GFAP), neurofilament light chain (NfL), ubiquitin carboxy‐terminal hydrolase L1 (UCH‐L1) and total tau (t‐tau) in urine of patients with acute cerebral damage. Methods Serum and urine samples were prospectively collected from patients with an acute ischemic stroke or intracerebral hemorrhage (target group) and compared to healthy subjects (control group); samples were measured using ultrasensitive single‐molecule arrays (Simoa®). Glomerular barrier function was assessed based on albumin–creatinine ratio (ACR); biomarker–creatinine ratios were calculated for correction of urine dilution. Results Ninety‐three urine–serum pairs in the target group and 10 urine–serum pairs in the control group were measured. The mean absolute concentration ± standard deviation in urine of the target and control groups were 184.7 ± 362.4 pg/ml and 27.3 ± 24.1 pg/ml for GFAP (r = 0.3 [Wilcoxon effect size], p = 0.007), 17.5 ± 38.6 pg/ml and 0.9 ± 0.3 pg/ml for NfL (r = 0.4, p < 0.005), 320.2 ± 443.3 pg/ml and 109.6 ± 116.8 pg/ml for UCH‐L1 (r = 0.26, p = 0.014), and 219.5 ± 255.8 pg/ml and 21.1 ± 27.1 pg/ml for t‐tau (r = 0.37, p < 0.005), respectively, whereas biomarker–creatinine ratio was significantly different only for NfL (r = 0.29, p = 0.015) and t‐tau (r = 0.32, p < 0.01). In patients with intact glomerular barrier (ACR < 30 mg/g), only NfL in urine was significantly different between the target and control group and showed a significant correlation with the respective serum concentrations (r = 0.58 [Pearson's correlation‐coefficient], p < 0.005). Conclusion All four investigated biomarkers could be measured in urine, with NfL and t‐tau showing the strongest effect size after correction for urine dilution. NfL revealed the most accurate relation between serum and urine concentrations in patients with intact kidney function.

IL-38 is an IL-1 family receptor antagonist with an emerging role in chronic inflammatory diseases. IL-38 expression has been mainly observed not only in epithelia, but also in cells of the immune system, including macrophages and B cells. Given the association of both IL-38 and B cells with chronic inflammation, we explored if IL-38 affects B cell biology. IL-38-deficient mice showed higher amounts of plasma cells (PC) in lymphoid organs but, conversely, lower levels of plasmatic antibody titers. Exploring underlying mechanisms in human B cells revealed that exogenously added IL-38 did not significantly affect early B cell activation or differentiation into plasma cells, even though IL-38 suppressed upregulation of CD38. Instead, IL-38 mRNA expression was transiently upregulated during the differentiation of human B cells to plasma cells in vitro, and knocking down IL-38 during early B cell differentiation increased plasma cell generation, while reducing antibody production, thus reproducing the murine phenotype. Although this endogenous role of IL-38 in B cell differentiation and antibody production did not align with an immunosuppressive function, autoantibody production induced in mice by repeated IL-18 injections was enhanced in an IL-38-deficient background. Taken together, our data suggest that cell-intrinsic IL-38 promotes antibody production at baseline but suppresses the production of autoantibodies in an inflammatory context, which may partially explain its protective role during chronic inflammation.