An imbalanced T-cell homeostasis plays an important role in the pathogenesis of systemic lupus erythematosus (SLE). Co-stimulatory and co-inhibitory molecules regulate T-cell differentiation, survival, and cytokine production. B- and T-lymphocyte attenuator (BTLA) is a co-inhibitory molecule which negatively regulates T-cell activation. The aim of this study was to investigate BTLA expression on regulatory and effector CD4⁺ T-cells in SLE patients with and without lupus nephritis (LN) during active and inactive disease. Therefore, peripheral blood of forty-one SLE patients and twenty-one healthy controls (HC) was phenotypically analyzed. Next, ex vivo stimulated T-cells were analyzed for the expression of BTLA on Th1-, Th2-, and Th17-effector cells by flow cytometry. Renal involvement was defined as biopsy-proven LN. Disease activity was assessed by SLE disease activity index (SLEDAI). Percentages of peripheral unstimulated BTLA⁺ CD4⁺ T-cells were significantly decreased in SLE patients with active disease. However, ex vivo stimulated Th1, Th2, and Th17 effector T-cells, expressed increased percentages of BTLA expression in active disease. In contrast, the BTLA expression on CD4⁺CD25⁺⁺CD127⁻ regulatory T-cells was not significantly different. BTLA seems to be an important co-inhibitory molecule in the T-cell homeostasis of patients with systemic lupus erythematosus and crucial for disease activity.

Recently, B cells with regulatory functions suppressing T-cell immunity were identified. Inflammation in the context of sepsis is characterized by a profound immune dysfunction increasing the patient’s risk for additional infections. The impact of endotoxemia on B-cell dynamics, regulatory B cells (Breg) and its contribution to immune dysfunction is unknown. It is the aim of the present study to characterize the dynamics of the B-cell compartment and Breg in an experimental human endotoxemia model. In this randomized placebo-controlled cross-over study, 20 healthy males received an intravenous injection of endotoxin (Escherichia coli lipopolysaccharide, LPS, 0.8 ng/kg body weight) or placebo (saline 0.9%) on two otherwise identical study days. B cells were analyzed by flow cytometry at baseline and repeatedly up to 72 h after endotoxin/placebo injection. Absolute CD19⁺ B cells counts showed a significant decrease 3 h after endotoxin injection. Memory B cells were partially depleted from the circulation; the total number of Breg was significantly diminished 3 h after LPS challenge. Production of anti-inflammatory interleukin (IL)-10 (IL-10) by Breg was unaltered after LPS challenge. Systemic B-cell activating factor (BAFF) levels were significantly increased with a maximum after 24 h and remained increased up to 72 h post-injection. Endotoxemia causes a transient depletion of memory B cells and Breg from the circulation. However, the functional capacity of B cells to produce IL-10 is not impaired.

In kidney transplant recipients, the cytomegalovirus (CMV) is frequently causing infection/reactivation and can trigger allograft rejection. To assess the risk of reactivation, the cellular immune response against CMV is increasingly assessed by cellular in vitro methods, such as the interferon (IFN)-γ ELISpot. In the current study we compared the IFN-γ ELISpot with our newly established CMV-specific ELISpot assays determining IL-17A, IL-21, IL-22, granzyme B, and perforin and correlated the results with flow cytometric data and clinical parameters. In 77 kidney transplant recipients, the highest frequency was observed for CMV pp65-specific cells secreting IFN-γ, followed by cells secreting IL-21 (62.9 and 23.2 Δ spot forming cells/10⁵ cells). We observed a positive correlation between the percentage of CMV-specific CD3+ CD4+ CD154+ cells and results of the CMV-specific IL-21 ELISpot (p = 0.002). Results of the CMV pp65-specific IL-21 ELISpot correlated negatively with kidney function (estimated glomerular filtration rate, p = 0.006) and were significantly higher in women (p = 0.005). IL-21, a cytokine involved in aging that is secreted by activated CD4+ T cells, may also impact on allograft function. Thus, the CMV-specific IL-21 ELISpot could become a new tool to assess if CMV seropositivity represents a hazard for the graft.

Background: Blinatumomab has been approved for the treatment of pediatric B‐cell acute lymphoblastic leukemia (B‐ALL). This study aimed to investigate the association between leukemia burden and the efficacy of blinatumomab in real‐world applications.Methods: A real‐world study was conducted by enrolling patients aged 0–18 years who were diagnosed with CD19‐positive B‐ALL and treated with blinatumomab between January 2021 and May 2023 from 14 centers in China.Results: A total of 304 patients were enrolled in this analysis. In the patients with > 5% blasts before blinatumomab (non‐complete remission, NCR group), 75.9% achieved complete remission (CR) and 69.0% of the NCR patients achieved minimal residual disease (MRD) negativity. Among the patients with ≤ 5% blasts but multiparametric flow cytometry MRD (MFC MRD) positive (MRD+ group), 98.9% achieved MRD negativity. Of the MFC MRD negative patients (MRD− group), the quantitative polymerase chain reaction MRD (qPCR MRD) and next‐generation sequencing MRD (NGS MRD) clearance rate was 60.0% (12/20) and 65.5% (19/29), respectively. Additionally, patients in the MRD− and MRD+ groups had significantly better outcomes than those in the NCR group, with 30‐month overall survival (OS) rates of 95.3% (95% CI: 91.4%–99.3%), 91.2% (95% CI: 85.0%–97.8%), and 77.6% (95% CI: 67.4%–89.4%), respectively (p < 0.001), and 30‐month event‐free survival (EFS) rates of 93.9% (95% CI: 89.6%–98.3%), 90.8% (95% CI: 85.0%–97.1%), and 56.7% (95% CI: 41.0%–78.6%), respectively (p < 0.001). In this study, 41.4% of patients experienced grade ≥ 3 adverse events (AEs), with hematological toxicity being the most common (33.2%). The severe adverse events, such as cytokine release syndrome (CRS) and neurotoxicity, occurred at a low rate, particularly grade ≥ 3, at 3.6% and 2.6%, respectively.Conclusions: Overall, these results indicate that blinatumomab is effective and well tolerated. Patients with a lower leukemia burden before blinatumomab administration tend to have better OS and EFS with fewer AEs.