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摘要： *** current state of non-HLA antibody testing in antibody-mediated rejection (AMR) remains not standardized and *** used 2 different commercial solid-phase assays to investigate the presence of non-HLA antibodies in a cohort of kidney transplant recipients stratified according to biopsy-proven AMR and HLA-donor-specific antibody *** 1 and 2 evaluated 60 and 39 different non-HLAs, of which 25 were shared. From the 25 common antigens, only 36% (n = 9) have a moderate correlation (r >= 0.6) in signal intensity. We observed significant heterogeneity in the prevalence of specific non-HLA antibodies detected between assay 1 and 2. Furthermore, the 2 assays showed substantial differences in the quantities, as well as specificities, of the positive non-HLA antibodies in each patient. Overall, the number of patients with positive antibodies that were detected by both assays was relatively low (median, 5 patients [interquartile range, 3-8] and 6 patients [interquartile range, 3-10] for transplant and biopsy samples, respectively, according to different antigens). Additionally, the panel of specific non-HLA antibodies found associated with AMR (and specifically with AMR/HLA donor-specific antibody negative) and graft loss was assay *** have shown that the current non-HLA antibody assays exhibit significant heterogeneity in terms of antibodies identified per patient and in association with rejection and graft loss.

摘要： Whether one or two agents added to post-transplant cyclophosphamide (PTCy) are needed in HLA-matched allogeneic hematopoietic stem cell transplantation (allo-HSCT) with peripheral blood stem cells (PBSC) is debated. We retrospectively compared PTCy in association with a calcineurin inhibitor (PTCy+CNI) or with a CNI plus mycophenolate mofetil (PTCy+CNI+MMF) in adult patients transplanted for acute myeloid leukemia in first complete remission and receiving PBSC in the period from 2010 to 2020. Propensity score matching was performed using exact matching for donor type (related or unrelated) and the nearest neighbor for other variables (i.e. age, adverse cytogenetics, Karnofsky performance status, patient and donor cytomegalovirus serology, conditioning intensity). Each group comprised 146 patients, with 63% in total undergoing matched unrelated-allo-HSCT. Median follow up was longer for PTCy+CNI (36 [IQR 31-39] months versus 25 [IQR 19-30] months for PTCy+CNI+MMF, p < 0.01). At 2 years, PTCy+CNI was associated with a higher incidence of extensive chronic GVHD (16% [95% CI 10-22] versus 6% [95% CI 3-12] for PTCy+CNI+MMF, p < 0.03) while no differences were observed for all the other transplant outcomes. Addition of MMF to PTCy and CNI may help to prevent extensive chronic GVHD in HLA-matched allo-HSCT with PBSC.

关键词： effector B cells   psoriasis   regulatory B cells  

摘要： Psoriasis is a chronic inflammatory skin disease driven by immune dysregulation. This study explores the role of B cells, particularly cytokine-producing subsets, in psoriasis pathogenesis. Although T cells, particularly Th17, have been well documented in psoriasis, recent evidence suggests that B cells contribute to the disease process. Flow cytometry analysis of 50 psoriasis patients and 20 healthy controls revealed a significant increase in IL-6-producing effector B cells (Beffs) and a decrease in IL-10-producing regulatory B cells (Bregs) in psoriasis patients. As IL-6 is pro-inflammatory and IL-10 is anti-inflammatory, this imbalance likely exacerbates inflammation in psoriasis. The study also examined the effects of guselkumab, an IL-23 inhibitor, on cytokine-producing B cells. The frequency of IL-6-producing Beffs in the blood was significantly (p < 0.05) elevated in patients with psoriasis compared with that in healthy controls. In contrast, the frequency of IL-10-producing Bregs in the blood was significantly (p < 0.05) decreased in patients with psoriasis compared with that in healthy controls. In 10 biologic-na & iuml;ve psoriasis patients, guselkumab significantly reduced IL-6-producing Beffs 4 weeks posttreatment, corresponding with a marked decrease in the Psoriasis Area and Severity Index (PASI). However, IL-10-producing Bregs showed no significant change over this period, suggesting that regulatory B cell recovery may require a longer timeframe or additional stimuli. These findings highlight the potential of B cells as biomarkers for disease activity and therapeutic response in psoriasis. The observed cytokine imbalance suggests that targeting B cell-mediated inflammation could be a novel therapeutic avenue. Further research is needed to assess long-term Breg dynamics and their role in maintaining immune homeostasis in psoriasis. This study reinforces the importance of both effector and regulatory B cells in psoriasis and suggests that monitoring the

关键词： Chicken interleukin-17   Infectious bursal disease virus   DNA vaccine   Adjuvant  

摘要： Infectious bursal disease virus (IBDV) is an important immunosuppressive virus in chickens, which caused an acute and highly contagious infectious disease and resulted in considerable economic losses in the world poultry industry. Although IBDV VP2 DNA vaccine has been extensively proved only partial protection, the efficacy of DNA vaccines against IBDV can be augmented by choosing potential molecular adjuvants. To investigate whether chicken IL-17 (chIL-17) is qualified for the molecular adjuvant, we constructed chIL-17 gene vector, coimmunized chickens with chIL-17 gene vector and IBDV VP2 DNA vector, and analyzed the effect of IL-17 gene on the immunogenicity of VP2 DNA vaccine. Results showed that co-administrated chIL-17 gene and VP2 DNA vaccine significantly increased IBDV-specific serum antibody titer, and promoted lymphocyte proliferation and interference-gamma (IFN-gamma) production. Mechanically, chIL-17 reduced virus titer in bursa of fabricius tissue and mortality of IBDV-infected chicken. More importantly, chIL-17 gene significantly enhanced the protection induced by the VP2 gene against virulent IBDV *** data show that chIL-17 is a promising immunoadjuvant to facilitate humoral as well as cellular immunity in a vaccine setting against IBDV, and suggest that it should be evaluated as a new DNA vaccine adjuvant in strategies for other poultry diseases.

摘要： Background and Aims: Epitranscriptomics, particularly N6-Methyladenosine (m 6A), which is the most common in mammals, represents a new therapeutic target for inflammatory conditions, such as cardiovascular diseases. Despite this, our understanding...