课程文献中心 更多>>

关键词： HLA-B   Indian   next generation sequencing   novel allele  

摘要： HLA-B*27:05:02:44 differs from HLA-B*27:05:02:01 by a single nucleotide in intron 1.

关键词： APC   antigen-presenting cell   BCLC   Barcelona Clinic Liver Cancer   EBRT   external-beam radiation therapy   HCC   hepatocellular carcinoma   ICI   immune checkpoint inhibitor   IFN   interferon   OS   overall survival   PD   programmed death protein   PD-L   programmed death ligand   RE   radioembolization   RT   radiation therapy   STING   immunogenic stimulator of interferon genes   TAA   tumor-associated antigen   TME   tumor immune microenvironment   90Y   yttrium-90  

摘要： Hepatocellular carcinoma is a leading and increasing contributor to cancer-related death worldwide. Recent advancements in both liver-directed therapies in the form of yttrium-90 (90Y) radioembolization (RE) and systemic therapy in the form of immune checkpoint inhibitors (ICI) have expanded treatment options for patients with an otherwise poor prognosis. Despite these gains, ICIs and 90Y-RE each have key limitations with low objective response rates and persistent hazard of out-offield recurrence, respectively, and overall survival remains low. However, each therapy's strength may mitigate the other's weakness, making them potentially ideal partners for combination treatment strategies. This review discusses the scientific and clinical rationale for combining 90Y-RE with ICIs, highlights early clinical trial data on its safety and effectiveness, and proposes key issues to be addressed in this emerging field. With optimal strategies, combination therapies can potentially result in increasing likelihood of durable and curative outcomes in later stage patients.

摘要： Background: Chronic inflammation is a well-recognized contributor to hypertension pathogenesis. However, the role of targeting inflammation in hypertension treatment, particularly through modulation of inflammatory markers like interleukin-6 (IL-6), remains less understood. We investigated the effects of antihypertensive medications with and without IL-6-lowering properties on long-term blood pressure (BP) control in a multiethnic cohort in the Netherlands. Methods: Participants from HELIUS cohort receiving hypertension treatment were followed over six years. BP control at follow-up was determined using WHO criteria. Due to unavailability of IL-6 data, a literature review was conducted to classify antihypertensives based on their IL-6-lowering properties - a proxy approach. Logistic regression models were used to assess associations between the IL-6-lowering potential of antihypertensives and BP control, both within and between antihypertensive classes. Effect modification by ethnicity was explored. Results: A total of 1510 participants were included (mean age 57 years, 62 % women). Within the calcium channel blocker (CCB) class, medications with IL-6-lowering properties (amlodipine and barnidipine) were associated with superior BP control (aOR 1.41, 95 % confidence interval 1.05-1.90) compared to other CCBs (lercanidipine, nifedipine, verapamil, clevidipine, diltiazem). No significant associations were observed within angiotensin receptor blockers (ARBs) or angiotensin-converting enzyme inhibitors (ACEIs), between different antihypertensive drug classes, nor across ethnic groups. Conclusion: Amlodipine and barnidipine were associated with better BP control compared to other CCBs. Our findings provide an important starting point for understanding the role of IL-6 in hypertension management. Further studies are warranted to confirm these observations by directly measuring IL-6 levels and investigating underlying mechanisms.

关键词： HLA-A*31:01:58   novel allele   sequence-based typing  

摘要： The HLA-A*31:01:58 allele differs from HLA-A*31:01:02:01 by one nucleotide substitution in codon 130 in exon 3.

关键词： HLA-B*51:385   novel allele   sequencing-based typing  

摘要： The HLA-B*51:385 allele differs from HLA-B*51:285 by a single non-synonymous nucleotide change in exon 3.

关键词： Paralichthys olivaceus   Interleukin-12   Interleukin-12 receptor subunit beta-2   Th1 cells differentiation   Adjuvant  

摘要： Interleukin-12 (IL-12) regulates the differentiation of CD4+ T lymphocytes into Th1 cells by binding to its receptor, thereby promoting cellular immunity. This study characterized IL-12 and its receptor (32 (IL-12R(32) in flounder (Paralichthys olivaceus) and investigated their interaction, effects on T cell proliferation and differentiation, and the adjuvant effects of IL-12. The recombinant IL-12 was successfully expressed, and the IL-12R(32 antibody was confirmed to specifically recognize IL-12R(32. IL-12 bound to IL-12R(32 at the cellular level. IL-12 stimulation increased leukocyte proliferation and the proportion of CD4+/IL-12R(32+ cells. Moreover, blocking IL-12R(32 with antibody reduced Th1 markers (STAT4, T-bet, IFN-y) and increased Th2 markers (JAK3, STAT6, GATA3). Immunization with rOmpV+IL-12 significantly upregulated CD4+/IFN-y+ cells on day seven, peaked the sIgM+ B lymphocyte response in the fourth week, and enhanced survival after Edwardsiella tarda challenge. In conclusion, IL-12 signaling effectively facilitates the differentiation of Th1 cells and negatively impacts the function of Th2 cells in flounder. This study provides new insights into the immune regulation of CD4+ T cells in teleosts and lays the foundation for understanding the cellular immune mechanisms of vaccines in aquaculture.

关键词： HLA   HLA-B*58:01:50   novel allele   sequence-based typing   Taiwanese  

摘要： Nucleotide substitution in codon 164 of HLA-B*58:01:01:01 results in the novel allele, HLA-B*58:01:50.

关键词： Anti-TNF   antibody formation   inflammatory bowel disease   loss of response   Saudi Arabia  

摘要： Background: The emergence of tumor necrosis factor inhibitors (anti-TNF) has considerably changed the management of inflammatory bowel disease (IBD) in patients who do not respond to traditional therapies. This study assesses the prevalence of anti-TNF drug levels (DLs) and antibodies (ATAbs) in patients with IBD in Saudi Arabia and explores their associations with IBD type and prior anti-TNF failure. Methods: This cross-sectional study included patients aged 14-75 years diagnosed with Crohn's disease (CD) or ulcerative colitis (UC), treated with anti-TNF medications at King Fahad Medical City over January 2016 to December 2022. Data were analyzed using descriptive statistics, Mann-Whitney U test, Kruskal-Wallis test, Pearson's Chi-squared test, and multinomial logistic regression. Results: Among 392 patients with IBD (median age, 31 years), 75.8% were diagnosed with CD and 24.2% with UC. Anti-TNF levels were subtherapeutic in 27.0% patients, therapeutic in 21.5%, and supratherapeutic in 51.5%. ATAbs were negative in 73.1% patients, weakly positive in 9.8%, and positive in 17.1%. Subtherapeutic anti-TNF levels were significantly associated with positive ATAbs (P < 0.001). Prior anti-TNF therapy failure was observed in 37.2% cases, with 15.3% showing immunogenicity. No significant demographic differences were noted across ATAbs groups. Conclusion: We highlight the prevalence of subtherapeutic and supratherapeutic anti-TNF levels among patients with IBD in Saudi Arabia and their association with ATAbs. The findings underscore the importance of monitoring anti-TNF DLs and ATAbs to optimize treatment outcomes in IBD management. Future research should focus on the longitudinal impact of these factors and explore genetic predictors of treatment response.

关键词： Brazil   HLA   HLA-C   new allele   next-generation sequencing   Rio de Janeiro  

摘要： The novel HLA-C*15:02:01:65Q allele was first described in a potential bone marrow donor from Brazil.

摘要： Background. The development of de novo donor-specific antibodies (dnDSA) and antibody-mediated rejection (AMR) remains a barrier to long-term graft and patient survival. Most dnDSA are directed against mismatched donor HLA-DQ antigens. Here, we describe a novel algorithm, which we have termed categorical amino acid mismatched epitope, to evaluate HLA-DQ mismatches. Methods. In this algorithm, amino acid residues of HLA-DQ protein were categorized into 4 groups based on their chemical characteristics. The likelihood of categorically mismatched peptides presented by the recipient's HLA-DRB1 was expressed as a normalized value, %Rank score. Categorical HLA-DQ mismatches were analyzed in 386 heart transplant recipients who were mismatched with their donors at the HLA-DQB1 locus. Results. We found that the presence of DQB1 mismatches with %Rank score <= 1 was associated with the development of dnDSA (P = 0.002). Furthermore, dnDSA increased the risk of AMR only in recipients who had DQ mismatches with %Rank score <= 1 (hazard ratio = 5.8), but the freedom from AMR was comparable between recipients with dnDSA and those without dnDSA if %Rank scores of DQ mismatching were >1. Conclusions. These results suggest that HLA-DQ mismatches evaluated by the categorical amino acid mismatched epitope algorithm can stratify the risk of development of dnDSA and AMR in heart transplant recipients.