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关键词： 多发性骨髓瘤   补体   免疫球蛋白   淋巴细胞亚群  

摘要： 探索不同分期的多发性骨髓瘤患者(Multiple Myeloma,MM)补体、免疫球蛋白和淋巴细胞亚群的临床意义。方法 选取2023年3月至2025年3月某院收治的90例MM患者,根据ISS分期将患者分为Ⅰ期、Ⅱ期、Ⅲ期。检测四组外周血补体(C3/C4)、免疫球蛋白(IgG/IgA/IgM)、淋巴细胞亚群。比较各期补体、免疫球蛋白及淋巴细胞亚群水平差异。结果 通过分析不同分期MM患者的患者的补体(C3/C4)、免疫球蛋白(IgG/IgA/IgM)、淋巴细胞亚群水平。发现Ⅲ期的C4、IgG/IgA、CD3+T/CD56+NK水平均高于Ⅰ期与Ⅱ期,C3低于Ⅰ期但高于Ⅱ期,IgM低于Ⅰ期和Ⅱ期,CD19低于Ⅱ期但高于Ⅰ期,差异均有统计学意义(P<0.05);结论 MM患者补体C4、免疫球蛋白IgG/IgA增高程度与疾病严重性密切相关,而IgM随疾病严重程度降低,淋巴细胞亚群无明显变化,建议在诊疗过程中监测C4和免疫球蛋白的变化,为病情检测和治疗方案优化提供客观依据。

关键词： allergic disease   birth cohort   HLA   phenome-wide association study   polygenic score   atopic march   immunoglobulin E   food allergy   atopic dermatitis   genetic predisposition  

摘要： The atopic march lacks early identification methods for high-risk children. In this study, we assessed whether the risk of atopic diseases in infants could be predicted using a polygenic score (PGS) for total immunoglobulin E (IgE) levels. The PGS estimated using the poly-genic model generated by PRS-CS was significantly correlated with log-transformed IgE levels (rho = 0.200, p < 2.2 x 10(-16)). Assessment of the risk from birth to 2 years of age in a Japanese birth cohort (n = 17,154) applying the estimated PGS revealed significantly elevated incidence risk ratios in the highest PGS quintile (Q5) compared with those in the reference quintiles (Q1-Q3) for food allergy (1.51-fold;95% confidence interval: 1.30-1.76), atopic dermatitis (1.30-fold;1.12-1.51), and both conditions (1.88-fold;1.46-2.43). These findings address critical gaps in allergy and PGS research among non-European populations, suggesting the contribution of genetic predisposition to IgE production in early-onset allergic diseases and supporting the use of PGS in early intervention.

关键词： Interleukin-1 receptor 2   Colorectal cancer   Immune checkpoint   CTLA-4   PD-1  

摘要： Colorectal cancer (CRC) continues to be a major global health challenge due to its high incidence and mortality rates, emphasizing the critical need for innovative therapeutic strategies. IL-1R2, a member of the IL-1 receptor family, plays a pivotal role in both tumorigenesis and antitumor immunity. However, its precise role in tumor development and its impact on immune checkpoint inhibitors (ICIs) therapy in CRC remain poorly understood. We examined tumor progression in wild-type and IL-1R2-deficient mice using an AOM/DSS-induced colitis-associated colorectal cancer model treated with combined ICIs therapy. Our findings revealed that IL-1R2 deficient mice exhibited a significant reduction in tumor burden, accompanied by alterations in the carcinogenic program and enhanced immunogenicity of tumor cells. Furthermore, the deletion of IL-1R2 resulted in an increased proportion of exhausted CD8+ T cells, a population commonly enriched for tumor antigen-specific T cells, suggesting an augmentation of tumor-specific immune responses. Moreover, IL-1R2 deletion upregulated genes linked to antigen presentation in dendritic cells, indicating enhanced activation of the adaptive immune system. Collectively, these findings position IL-1R2 as a promising therapeutic target for improving the efficacy of treatment strategies in CRC.

关键词： adoptive cell therapy   degron   drug-responsive domain   membrane-bound interleukin-15   regulation   synthetic biology   TIL   tumor-infiltrating lymphocytes  

摘要： Adoptive cell therapy using tumor-infiltrating lymphocytes (TIL) has demonstrated great potential for patients with treatment-refractory metastatic melanoma. However, the need for interleukin-2 (IL-2) co-administration during TIL cell therapy limits patient eligibility and restricts treatment to intensive care units due to the risk of severe side effects. Instead, engineering TIL with membrane-bound interleukin-15 (mbIL15) has the potential to promote TIL expansion, antitumor activity, and persistence of CD8+ T cells, without the use of IL-2. cytoTIL15 cells express mbIL15 fused to a drug-responsive domain (DRD) that is regulated by the Food and Drug Administrationapproved small-molecule drug acetazolamide (ACZ). As such, cytoTIL15 cells are manufactured with ACZ instead of IL-2, in the presence of engineered feeder cells. The cytoTIL15 cell product exhibits ACZ dose-dependent expansion and persistence in vitro and in vivo and potent tumor-killing activity in human melanoma models in the absence of IL-2. In patientinfiltrating cytoTIL15 cells to be highly cytotoxic and less exhausted than non-engineered TIL. This novel platform creates a powerful, IL-2-free TIL cell therapy with a potentially improved tolerability and safety profile, while allowing individualized pharmacologic regulation of the TIL product.

关键词： antitumor immunity   antiviral immunity   CD8+ T cells   dendritic cells   galectin-4  

摘要： Galectin-4 (Gal-4), a member of the beta-galactoside-binding galectin family, plays a role in various physiological processes, including tumor progression and intestinal disorders. However, its contribution to adaptive immunity remains poorly understood. In this study, Gal-4 is identified as a critical factor for effective generation of CD8+ T cell responses against tumors and viral infections. Gal-4-deficient mice exhibit significantly enhanced tumor growth in syngeneic mouse cancer models, attributed to impaired CD8+ T cell responses. Similarly, antiviral CD8+ T cell responses against lymphocytic choriomeningitis virus (LCMV) are profoundly diminished in Gal-4-deficient mice. This is not due to CD8+ T cell-intrinsic defects but instead linked to decreased surface expression of antigen-MHC-I complexes on dendritic cells. Building on these findings, the therapeutic potential of Gal-4 is investigated. Administration of Gal-4 enhances the efficacy of cancer vaccines and PD-1 blockade cancer therapy to improve outcomes in tumor-bearing mice. Additionally, systemic administration of Gal-4 markedly amplifies antiviral CD8+ T cell responses against LCMV. Collectively, these results underscore the pivotal role of Gal-4 in modulating CD8+ T cell immunity and highlight its promise as a therapeutic target for the development of novel immunotherapeutics against cancer and viral diseases.

关键词： kidney transplant   antibody-mediated rejection   donor-specific antibodies   graft outcomes   HLA screening  

摘要： Donor-specific HLA antibodies (DSA) are related to antibody-mediated rejection (ABMR) and graft failure. The rationale and frequency of screening for anti-HLA antibodies in stable patients are not established. The aim of our study is to evaluate the impact of early DSA appearance in the first month post-transplant on graft outcomes. All kidney transplant recipients between 1/1/2012-12/31/2022 with anti-HLA antibody screening by Luminex during the first month post-transplant were included. Patients with preformed or historical DSA and those with DSA detection after graft loss were excluded. The mean fluorescence intensity cut-off was 1,500. Three hundred fifty-three patients were included and the median time from transplant to first antibody sample was 30.0 days. During 3.8 years of follow-up, graft loss occurred in 9.1% and 19.5% had ABMR. A total of 8.5% developed early-DSA in the first month. Patients with early-DSA detection had more HLA sensitization at the time of transplant (p < 0.001). Multivariable analysis showed that the presence of early-DSA was an independent risk factor for ABMR. In conclusion, sensitized patients at the time of transplant have a higher risk of DSA formation in the first month, probably reflecting alloimmune memory, therefore early HLA antibody screening should be performed in this high-risk population.

关键词： spondyloarthritis   HLA-B*27-negative   immunogenetics   Romanian cohort   cross-reactivity  

摘要： This study examined the distribution and disease associations of non-HLA-B*27 HLA-B alleles in Romanian spondyloarthritis (SpA) patients, aiming to address the underrepresentation of Eastern European populations in immunogenetic research. Methods: We analyzed 263 HLA-B*27-negative patients from Northeastern Romania fulfilling ASAS criteria. HLA-B genotyping was performed at two-digit resolution, and allele distributions were compared with two Romanian HLA-B*27-negative control groups (n = 335 and n = 1705 cases), using chi-square testing and logistic regression. Compared to controls, HLA-B*47 (p = 0.0007) and HLA-B*54 (p = 0.0013) were significantly enriched, while HLA-B*40 was underrepresented (p = 0.0287). Notably, HLA-B*54 was observed exclusively in axial SpA. Within the cohort, both HLA-B*13 and HLA-B*57 alleles were associated with psoriasis, while HLA-B*37 and HLA-B*41 alleles were clustered within the reactive arthritis group. The HLA-B*35 and HLA-B*18 alleles were the most frequently observed alleles across most clinical phenotypes. When comparing the frequency of HLA-B associations, the most common genotypes among SpA patients were B*08-B*18, B*13-B*35, and B*35-B*51. Notably, B*08-B*18 was more frequent in patients with radiographic sacroiliitis grade >= 2, while B*35-B*51 was more frequent in those with confirmed systemic inflammation, as indicated by elevated CRP or ESR levels. Analysis of peptide-binding patterns revealed a cluster of risk alleles, HLA-B*08, B*18, B*35, B*40, and B*54, sharing similar features, distinct from the canonical profile of B*27. These findings highlight the contribution of non-B*27 HLA-B alleles to SpA susceptibility in an Eastern European population and support the notion that HLA-B*27-negative SpA may represent a distinct clinical and immunological entity, driven by alternative pathogenic mechanisms. They also emphasize the importance of population-specific immunogenetic profiling and support expanding genetic characterizat

关键词： advanced cardiac imaging   Castleman disease   giant coronary artery aneurysm   interleukin-6   AAA   abdominal aortic aneurysm   CAA   coronary artery aneurysm   CD   CMR   cardiac magnetic resonance   CT   computed tomography   ECG   electrocardiogram   ECM   extracellular matrix   IL   interleukin   MMP   matrix metalloproteinase   RCA   right coronary artery   TAA   thoracic aortic aneurysm  

摘要：

关键词： 天麻钩藤饮   血管性痴呆   星型胶质细胞   TNF-α/STAT3/α1ACT通路  

摘要： 目的：探究天麻钩藤饮对血管性痴呆模型大瘤坏死因子-α（TNF-α）/信号转导与转录激活因子3（STAT3）/α1-抗胰蛋白酶C末端尾片段?（α1ACT）通路及A1星型胶质细胞的影响。方法：将72只雄性SD大鼠随机分为假手术组，模型组，天麻钩藤饮高、中、低剂量组（5.13、10.26、20.52 g·kg?1）及尼莫地平西药组（8.1 mg·kg?1），每组12只。采用永久性双侧颈总动脉闭塞法造模后干预4周。通过新物体识别实验评估学习记忆能力；强迫游泳实验观察行为症状；酶联免疫吸附测定?检测海马组织白细胞介素6（IL-6）、CC趋化因子配体2（CCL2）水平；尼氏染色观察海马神经元形态；TUNEL染色检测细胞凋亡；免疫组化检测脑源性神经营养因子（BDNF）、胶质纤维酸性蛋白（GFAP）、髓鞘碱性蛋白（MBP）阳性表达；蛋白免疫印迹法测海马组织TNF-α、TNF受体1（TNFR1）、磷酸化STAT3（p-STAT3）、α1ACT、IL-6、补体C3（Complement Component 3）、BDNF、S100钙结合蛋白A10（S100A10）、GFAP蛋白表达。结果：与假手术组比较，模型组大鼠新物体相对识别指数显著降低（P<0.01），被动漂浮时间延长、次数增多（P<0.01）；海马组织IL-6、CCL2表达升高（P<0.01），尼氏染色显示神经元数量减少、尼氏小体丢失（P<0.01），MBP阳性表达降低（P<0.01），细胞凋亡增多（P<0.01），BDNF阳性表达减少（P<0.05），GFAP阳性表达升高（P<0.01），TNF-α、TNFR1、p-STAT3、α1ACT、IL-6、C3蛋白表达升高（P<0.01），BDNF、S100A10降低（P<0.01）。与模型组比较，天麻钩藤饮各剂量组新物体相对识别指数显著升高（P<0.05），被动漂浮时间缩短、次数减少（P<0.01，P<0.05），IL-6、CCL2表达降低（P<0.01），神经元数量增加（P<0.01，P<0.05），MBP阳性表达增加（P<0.01），细胞凋亡减少（P<0.01），BDNF阳性表达增加（P<0.05），GFAP阳性表达降低（P<0.01），TNF-α、TNFR1、p-STAT3、α1ACT、IL-6、C3蛋白表达降低（P<0.01），BDNF、S100A10蛋白表达升高（P<0.01）。结论：天麻钩藤饮治疗可以通过TNF-α/STAT3/α1ACT通路抑制血管性痴呆大鼠A1型星型胶质细胞激活，减轻神经元凋亡，提高学习记忆能力。

关键词： HLA-DQB1*03:570   new allele   NGS  

摘要： HLA-DQB1*03:570 differs from HLA-DQB1*03:02:01:02 by a single nucleotide polymorphism in exon 4, codon 207.