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关键词： 紫癜性肾炎   BAFF   IL-21   中医证型  

摘要： 目的：探讨过敏性紫癜（Henoch-Schonlein syndrome，HSP）患儿发生肾损害与血清B淋巴细胞活化因子（B lymphocyte activating factor，BAFF）、白介素21（interleukin-21，IL-21）表达的相关性，以期进一步明确儿童HSPN的病因、发病机制，为临床诊治提供依据。方法：选取2021年1月-2021年12月在我院住院的过敏性紫癜患儿，根据是否发生肾损害分为紫癜性肾炎组（HSPN组）及过敏性紫癜组（HSP组），选择同时期在我院门诊体检的健康儿童15例，检测各组患儿血清BAFF、IL-21水平，并收集临床一般料以及24h尿蛋白定量（24hUTP）、血肌酐（Scr）、尿素氮（BUN）、尿酸（UA）等，并估算患儿肾小球滤过率（eGFR）。比较各组血清BAFF、IL-21表达水平，分析与HSPN发病及中医证型的相关性。结果：1.一般情况：男性66例，女性39例，男女比例为1.69:1，三组间年龄及性别比较均无统计学差异（P>0.05）。***组、HSPN组BAFF、IL-21水平高于健康对照组（P<0.01）；HSPN组BAFF、IL-21水平高于HSP组（P<0.01）。患儿血清IL-21、BAFF水平呈正相关（P<0.01）。***患儿BAFF表达水平与Scr及BUN水平呈正相关，与eGFR呈负相关（P<0.05）；与24hUTP、UA、是否腹痛及关节痛无相关性（P>0.05）。HSPN患儿IL-21表达水平与eGFR呈负相关（P<0.05）；与24hUTP、Scr、BUN、UA、是否腹痛及关节痛无相关性（P>0.05）。***、IL-21水平是HSP患儿发生肾损害的危险因素（P<0.05）。5.阴虚夹瘀证、气阴两虚夹瘀证BAFF、IL-21水平高于风热伤络证、血热夹瘀证（P<0.05）。结论：HSPN患儿血清BAFF、IL-21水平明显增高，并与疾病严重程度呈正相关；BAFF、IL-21是HSP患儿发生肾损害的危险因素；阴虚夹瘀证、气阴两虚夹瘀证BAFF、IL-21表达水平明显增高。

摘要： Cutaneous allergen sensitization (CAS) underlies atopic dermatitis (AD) and leads to various allergic symptoms, including food allergy and anaphylaxis. IL-13 expression by T follicular helper T (TFH) has been reported to be involved in generating high-affinity IgE antibodies and causing systemic anaphylaxis.1, 2 However, the mechanisms by which IL-13 triggers IgE-mediated allergic responses remain poorly defined. In the present study, we elucidate the role of IL-13 in the CAS-mediated mechanism by which high-affinity IgE antibodies are produced when the same allergen is introduced at a distal site in the secondary sensitization. The CAS model system using mice lacking the cell lineage-specific IL-13 receptor (IL-13R) demonstrated that dendritic cells (DCs), but not T or B cells, are critical in the high-affinity IgE-mediated anaphylactic response. The IL-13 signal in type 2 conventional DCs (cDC2s) enhanced the expression of MHC class II and CD301b, which was essential for the recall of type 2 responses, inducing the production of high-affinity IgE antibodies. Similar IL-13R-expressing DCs were identified in allergic rhinitis and food allergy patients with a history of AD. These findings strongly suggest the importance of DC-specific IL-13 signaling in CAS-induced allergic reactions associated with the atopic march, which is common in human AD patients.

摘要： BACKGROUND:The introduction of posttransplant cyclophosphamide (PTCy) for prophylaxis against graft-versus-host disease (GVHD) has led to an increase in the number of transplants from haploidentical donors. Accordingly, we aimed to understand the impact of HLA epitope mismatch on the outcomes of haploidentical hematopoietic stem cell transplantation (HSCT) with prophylaxis against GVHD. METHODS:This retrospective study included 1037 patients who underwent their first HSCT for hematologic malignancies from haploidentical peripheral blood donors in a Japanese registry between 2011 and 2019. In total, 542 patients received PTCy and 495 received antithymocyte globulin-based GVHD prophylaxis. RESULTS:In patients with high-risk disease who received PTCy, higher class I Predicted Indirectly ReCognizable HLA Epitopes (PIRCHE-I) scores were associated with a significantly lower risk of relapse, leading to a higher overall survival (OS: high PIRCHE-I patients compared with low PIRCHE-I patients: relapse: hazard ratio [HR], 0.67; 95% confidence interval [CI], 0.46-0.98; P = 0.040; mortality: HR, 0.69; 95% CI, 0.46-0.99; P = 0.042). In patients with standard-risk disease who received antithymocyte globulin, a significant association between class II PIRCHE (PIRCHE-II) and a lower incidence of nonrelapse mortality (NRM) leading to higher OS was observed (high PIRCHE-II patients compared with low PIRCHE-II patients, NRM: HR, 0.41; 95% CI, 0.19-0.86; P = 0.019; OS: HR, 0.55; 95% CI, 0.32-0.94; P = 0.030). CONCLUSIONS:These findings suggest the differential effects of T-cell epitope matching based on GVHD prophylaxis after haploidentical HSCT. Pretransplant disease status may also be important for understanding the graft-versus-leukemia effect of mismatched HLA in haploidentical HSCT using PTCy.

关键词： T-cells  

摘要： Developing an effective HIV-1 vaccine is a global health priority, but HIV-1 mutational escape from T cells poses a challenge. While escape from human leukocyte antigen class I (HLA-I)–restricted CD8+ T cells is well characterized, less is known about HLA-II–restricted T cell escape. We used computational methods to identify 149 sites across the HIV-1 clade B genome under HLA-II–associated selection. Functional assays, including activation-induced intracellular cytokine staining and enzyme-linked immunospot for interferon-γ, revealed diverse mechanisms of HIV-1 adaptation to HLA-II–associated immune pressure, ranging from loss to sustained antigen recognition. T cell receptor and RNA sequencing demonstrated variable clonotype overlap of T cell clones to recognize adapted versus non-adapted peptides, with cells targeting adapted peptides exhibiting a dysfunctional transcriptomic state. Moreover, incorporating HLA-II–associated adaptation strengthened the correlation between Gag-specific viral adaptation and poor disease outcomes. Last, we mapped viral regions prone to HLA-II–associated adaptation and found that these adaptations can increase in frequency within populations. Copyright © 2025 The Authors, some rights reserved.

关键词： 结节性皮肤病病毒   A27L蛋白   可溶性表达   多克隆抗体  

摘要： 旨在获得结节性皮肤病病毒（LSDV）的重组A27L蛋白并制备其多克隆抗体，将密码子优化的A27L基因进行人工合成，随后克隆至pET-28a表达载体中，成功构建重组表达质粒pET-28a-A27L，将其转化入BL21(DE3)感受态细胞中，用0.5 mmol/L IPTG进行诱导表达，利用SDS-PAGE和Western-blot对表达产物进行分析。经优化表达条件获得分子质量约为19 kDa的可溶性重组A27L蛋白。采用High Affinity Ni-Charged Resin FF对可溶性表达产物进行纯化，成功获得高纯度的重组A27L蛋白，将其免疫新西兰大白兔4次后收集血清，Western-blot分析和间接免疫荧光鉴定结果表明A27L多克隆抗体可特异识别BHK-21细胞中表达的重组A27L蛋白。本研究利用大肠杆菌成功表达了可溶性重组LSDV A27L蛋白，并制备出特异的A27L多克隆抗体，为深入研究A27L蛋白的生物学功能以及研发结节性皮肤病疫苗和诊断技术提供了基础。

摘要： The VIVID-1 study is a phase 3 randomized controlled trial assessing the efficacy and safety of mirikizumab in moderate-to-severe active Crohn's disease.¹ The study confirms the advantage of selective IL-23 inhibition, while the treat-through design and the choice of composite coprimary endpoints represent an innovative strategy in conducting clinical trials in Crohn's disease. © 2024 Elsevier Inc.

关键词： 番茄褪绿病毒(ToCV)   外壳蛋白(CP)   原核表达   多克隆抗体   制备  

摘要： 为建立番茄褪绿病毒（Tomato chlorosis virus,ToCV）的快速检测技术，通过RT-PCR技术克隆病毒的主要外壳蛋白（Coat protein,CP）基因，利用Gateway技术将其重组至原核表达载体中，转化至大肠杆菌（Escherichia coli）BL21菌株中诱导表达，将纯化后的CP作为抗原免疫日本大耳兔制备ToCV CP多克隆抗体。间接ELISA显示ToCV CP多克隆抗体的效价为1∶12 800;Western blot和田间试验结果显示多克隆抗体有很好的特异性和灵敏度。ToCV CP多克隆抗体可用于田间ToCV的检测。

关键词： 抗原   结核分枝杆菌复合群   ECX   间接ELISA  

摘要： 本研究通过前期已构建好一些优势抗原的表达载体库，以生物信息学工具分析候选抗原的理化性质、二级结构、B细胞抗原表位，选择优势抗原，以纯化后的融合抗原ECX作为包被抗原，将HRP标记的ProteinG作为酶标的二抗，成功建立了一种用于多动物结核分枝杆菌复合群间接ELISA 诊断的方法。该方法适用于实验室样品批量检测，其敏感性为0.912，特异性为0.949。应用本研究建立的动物结核分枝杆菌间接ELISA法和商品化动物结核分枝杆菌夹心ELISA抗体检测试剂盒（INGENASA，西班牙），两种方法共检测犬、猫、野生动物、SPF实验动物血清共552份。其中间接ELISA方法共检出6份血清抗体阳性，阳性检出率为1.09%（6/552）；商品化夹心法试剂盒共检出8份血清抗体阳性，阳性检出率为1.45%（8/552）；两者之间阳性重合数为6份，阳性重合率为85.72%（6/7）；阴性重合数为544份，阴性重合率为99.82%（544/545）。结果表明，两种诊断方法的检测结果具有较高的一致性。本方法的建立，与国外商品化试剂盒比较，不但有望实现这类检测产品的国产替代，同时实现了一种方法对不同物种来源血清的快速检测。

关键词： Classical swine fever virus   E2 subunit vaccine   IL-28B  

摘要： The E2 subunit vaccine has been considered a promising alternative to an attenuated classical swine fever (CSF) vaccine. However, it fails to induce a good cellular immune response. Given that immunogenic adjuvants can regulate the cellular immunity to achieve a maximum efficacy against antigens, immunostimulatory effects of porcine IL-28B on the CSF virus (CSFV) E2 subunit vaccine were evaluated in the present study. We expressed recombinant proteins E2-IL28B, E2, and IL-28B using CHO-S mammalian cells as an antigen expression platform, and three types of CSFV E2 subunit vaccines based on antigens E2-IL28B, E2 + IL-28B, and E2 were prepared, respectively. We found that both E2-IL28B and E2 + IL-28B antigens exhibited superior immunogenicity with dramatically induced antibody titers and neutralizing antibody levels than the E2 alone. Moreover, E2-IL28B or E2 + IL-28B, instead of E2, boosted cellular immune responses via obviously increasing the percentages of CD3CD4 T lymphocytes, promoting the lymphocyte proliferations, and enhancing the release of Th1-type cytokines. All results revealed that the inclusion of IL-28B, whether fused or mixed with E2, significantly elevated E2-induced immune potencies, suggesting that IL-28B could be used as a molecular adjuvant to optimize the design of E2 subunit vaccine for more effective controls of the CSF disease. KEY POINTS: • New CSF E2 subunit vaccine candidates were developed in which IL-28B was an immunoadjuvant • IL-28B significantly elevated the E2-induced immune potency whether it was fused or mixed with E2 • This study provided novel insights into the immunoregulatory properties of IL-28B used for the optimized subunit vaccine design.

摘要： Th1/Th2 balances may play a vital role in the processes of inflammation and fibrosis. The Th1/Th2 paradigm can be evaluated by representing IFN-gamma for Th1 and IL-4 for Th2. OM-85 BV encouraged preferential development of the Th1-type immunity characterized by amplified IFN-gamma and decreased IL-4 production. This study aimed to evaluate the inhibitory effect of OM85 on bleomycin (BLM)-induced pulmonary fibrosis in C57 and its possible mechanisms. In vitro experiments demonstrated that OM85 exhibited no significant toxicity to HELF cells. OM-85 inhibited the TGF-beta 1-induced protein expression of Notch1 and Hes1 and reduced the fibrosis-related marker profiles, such as collagen I, collagen III, fibronectin, P21, and alpha-SMA, following TGF-beta 1 treatment of these cells. Immunofluorescence also revealed that OM-85 decreased the expression of alpha-SMA induced by TGF-beta 1 in HELF cells. In the vivo experiments, a pulmonary fibrosis model was established by administering three intratracheal doses of BLM (1 mg/kg). The BLM-OM85 group was exposed to an aerosol containing 10.5 mg of OM-85 dissolved in 10 mL of sterile PBS on days 42, 44, 46, 49, 51, and 53. BLM-induced pulmonary fibrosis, leading to increased levels of lung hydroxyproline, total cell count, macrophages, neutrophils, lymphocytes, and the expression of TGF-beta 1 as well as Notch1 and Hes1 in lung tissue, along with fibrosis-associated proteins such as collagen I, collagen III, fibronectin, P21, and alpha-SMA. Additionally, the Th1 response was suppressed, as evidenced by decreased IFN-gamma in the bronchoalveolar lavage fluid (BALF), while the Th2 response was amplified, marked by increased IL-4 levels in BALF. Moreover, morphological assessments showed that BLM caused increased Ashcroft scores, relative collagen content, and an expanded damaged area, as well as an increased optical density (OD) of collagen I. The administration of OM-85 significantly mitigated these effects. These findings sugge