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关键词： full-length sequence   HLA-B   next-generation sequencing   novel allele   south India  

摘要： One nucleotide change (C -> T) in intron 1 of HLA-B*13:01:01:01 results in the novel HLA allele HLA-B*13:01:01:12.

关键词： Benign prostatic hyperplasia   Elderly   Homocysteine   IL-6   Diagnosis  

摘要： Objective: To investigate the diagnostic value of serum metabolic markers such as HCY, sdLDLC, Crea, inflammatory factor IL-6 and prostate-specific antigen in elderly patients with prostatic hyperplasia (BPH). Methods: 150 senile patients with hyperplasia of prostate were selected as observation group and 169 healthy senile patients were selected as control group. The tPSA, fPSA, fPSA/tPSA and prostate size data of the two groups were collected, and serum samples of the subjects were collected for the detection of HCY, sdLDL, Crea, IL-6 and other indicators. Univariate analysis, correlation analysis and logistic regression analysis were conducted to analyze the relationship between each index and senility prostatic hyperplasia. The diagnostic efficiency of each serum metabolite was analyzed by receiver operating characteristic curve (ROC). Results: Serum levels of tPSA, fPSA, Crea, HCY, sdLDL-C and IL-6 were significantly increased, fPSA/tPSA ratio and HDL were significantly decreased, and TCHO, TG and LDL had no statistical significance. Serum tPSA and fPSA levels were positively correlated with prostate size, serum IL-6, Crea and HCY levels were positively correlated with tPSA and fPSA levels, and serum sdLDL-C levels were negatively correlated with fPSA levels. Logistic regression analysis showed that tPSA, fPSA, prostate size, HCY, Crea and IL-6 were risk factors for prostate hyperplasia. HDL and fPSA/tPSA are protective factors for benign prostatic hyperplasia. ROC curve analysis showed that the sensitivity and specificity of fPSA/tPSA and IL-6 were 82.7% and 72%, 83.4% and 80.5%, and the area under ROC curve were 0.840 and 0.825, respectively. tPSA and fPSA combined with HCY, IL-6 and Crea had the best diagnostic efficiency, with the area under ROC curve reaching 0.881, specificity and sensitivity reaching 84% and 77.3%, respectively. Conclusion: The combined detection of prostate-specific antigen, HCY, Crea and IL-6 can significantly improve the diagnostic ef

关键词： genomic full-length   HLA-DRB1*13:97:01   PacBio sequencing  

摘要： The complete genomic sequence of HLA-DRB1*13:97:01 was determined using a PacBio sequencing approach conducted in China.

关键词： Tumor-infiltrating lymphocytes   Cancer Immunotherapy   Combinatory therapy  

摘要： Background & Aim Tumor-infiltrating lymphocyte (TIL) therapy has shown limited efficacy in cold tumors due to impaired infiltration, suppressive microenvironment, and defective tumor antigen presentation. Recent advancements in expansion protocols and combination therapies offer promising strategies to address these challenges. Methodology TILs from renal cell carcinoma (RCC), glioblastoma (GBM), prostate cancer (PRC) and pancreatic cancer (PCA) were expanded with IL-2/IL-15/IL-21 in a closed perfusion bioreactor. TIL pharmacokinetics (PK) and tumor infiltration were analyzed using T-cell receptor (TCR) next-generation sequencing, while pharmacodynamics (PD) were assessed by FACS, RNA-seq and ELISA. Results Expanded TIL products exhibited high CD8/CD4 ratios, robust cytokine production, degranulation and autologous tumor-specific killing. Patients received a single cyclophosphamide dose one day before infusion, followed by IL-2 administrations. GBM patient demonstrated complete tumor regression 22 days after the second infusion, followed by increased IFN-γ levels and memory T-cell frequency in the blood. High tumor infiltration of TIL-derived clonotypes, enhanced immunological synapse and T-cell activation RNA signatures were observed in tumor samples after the infusions. CD4+ TILs displayed high TCR diversity but limited infiltration, while CD8+ TILs showed robust tumor infiltration and expansion in vivo . RCC patient evolved from stable disease (SD) after two infusions to partial response (PR) post-third infusion, with sustained good clinical condition. PCA and PRC patients transitioned from SD post-first infusion to PR after the second dose. Notably, PRC achieved a complete response exceeding five years, with undetectable PSA levels when the third infusion was combined with anti-PD-1. This combination expanded previously infused TIL-derived clonotypes in blood and tumor, resulting in sustained persistence and infiltration. Across all cases, high TIL infiltration

关键词： gene deletion   haplotypes   histocompatibility testing   HLA-B gene  

摘要： Targeted next generation sequencing-based HLA typing of a 17-year-old female transplant patient showed homozygosity for the HLA-B allele. The segregation analysis of HLA haplotypes of family members only allowed the conclusion that the B-allele was deleted in the haplotype inherited from the father and accordingly paternal grandfather, resulting in false homozygous genotyping. The subsequent whole-genome sequencing of the patient and her father confirmed an approximately 85 kb deletion at 6p21.33 from the 5 ' end of the HLA-B to the 3 ' end of the HLA-C gene extending telomeric to HLA-C.

关键词： haploidentical stem cell transplantation donors and patients   HLA   KIR   KIR genotype   transplantation  

摘要： There is limited information regarding the influence of KIR genotype, compared to the HLA system, in haploidentical haematopoietic stem cell transplantation (haplo-HSCT). This study aimed to determine the frequencies of KIR genotypes in Spanish haematologic patients undergoing haplo-HSCT. A study was conducted on 113 oncohaematological patients and their donors, treated across five centres that are members of the Spanish Working Group in Histocompatibility and Transplant Immunology (GETHIT) and the Spanish Haematopoietic Transplantation and Cell Therapy Group (GETH-TC). KIR typing was performed using PCR-rSSO or PCR-SSP. KIR genotypes were identified using the KIR Allele Frequency Net Database. Among donors, the most frequent KIR genotypes were Type 1 (28.3%), Type 2 (12.4%) and Type 4 (10.6%). In patients, Genotypes 1 (23.9%), 4 (23%) and 2 (14.2%) were most prevalent. Donors exhibited AA centromeric (46%) and telomeric (59.3%) types, while patients had a higher AB centromeric frequency (52.2%). Differences were observed in the BB centromeric type (3.5% patients;16.8% donors, p = 0.002). The AB KIR genotype was the most common (70.8% donors;75.2% patients). Most were classified as 'neutral' (61.9% donors;73.5% patients). B-content score1 was the most common (48.7% patients;33.6% donors). Notably, classification as best was rare (2.7% patients;16.8% donors, p = 0.002). The study highlights the distribution of KIR genotypes in haplo-HSCT patients and donors, with Genotypes 1, 2 and 4 being the most prevalent. AB KIR genotypes and B-content score 1 were dominant. Moreover, KIR genotypes ID may serve as criteria for future investigation about the immunogenetic predisposition to malignant haematological diseases.

关键词： bone marrow transplantation   C*01:285Q   HLA-C   NGS  

摘要： HLA-C*01:285Q differs from HLA-C*01:02:01:01 by a single nucleotide substitution in the start codon.

关键词： Coixol   Ulcerative colitis   IL17A signaling pathway   Mitophagy   Inflammation   Molecular docking  

摘要： Coicis Semen, a versatile food known for its nutraceutical properties, is valued for its edibility. Coixol, the principal bioactive component of Coicis Semen, exhibits potent anti-inflammatory effects, highlighting its potential in managing inflammatory diseases. This study investigates the efficacy of Coixol in alleviating ulcerative colitis (UC) and describes its underlying mechanisms. By integrating network pharmacology with transcriptome profiling, we demonstrate that Coixol modulates genes involved in interleukin (IL)17 A signaling pathway and autophagy. We also predict the binding potential of Coixol and its target proteins using molecular docking. We found that Coixol notably reduced weight loss, colonic injury, inflammatory cytokines, and mitochondrial damage in dextran sulfate sodium (DSS)-induced mice. Moreover, Coixol greatly inhibited the IL17A signaling pathway and boosted mitophagy-related gene and protein expressions in both DSS-induced mice and IL17Astimulated RAW264.7 cells. Molecular docking further revealed Coixol's ability to bind tightly and stably to IL17A, IL17RA, TNF receptor-associated factor 6 (TRAF6), nuclear factor kappa-B (NF-kappa B), and Inhibitor of Nuclear Factor kappa B alpha (IKB alpha). Taken together, these data suggest that Coixol's therapeutic potential in UC is mediated by its inhibition of the IL17A signaling pathway and interactions with relevant targets, thus promoting mitophagy. This positions Coixol as a functional food candidate for managing UC.

关键词： HLA   Haploidentical stem cell transplant   Donor-specific antibodies   Graft failure   Reduced-intensity conditioning  

摘要： Background: Donor-specific (DSA) anti-HLA antibodies can adversely influence outcomes of haploidentical hematopoietic stem cell transplantation (haplo-HSCT). Methods: Patients who received a haplo-HSCT from a sibling after reduced-intensity conditioning (RIC) and had a virtual cross match against donor's HLA typing performed and a positive single-antigen microspherebased immunoassay test were studied. DSA were considered positive with a mean fluorescence intensity (MFI) >= 1000. Results: Anti-HLA DSA >= 1000, median 2623 (range 1000-13,235) MFI were documented in 27/65 (42 %) patients. In 14 (21.5 %) patients, antibodies were anti-HLA class I, in 18 (27.7 %) anti-HLA class II, and in 6 (9.2 %) against both. Overall (OS) and event-free survival (EFS) were lower in patients with anti-HLA Class I DSA (p = 0.026 and p = 0.037, respectively). One-year mortality was higher with anti-HLA DSA of any class (p = 0.009). Nine (64.3 %) of 14 patients with DSA anti-HLA class I died, vs. 11/18 (61 %) with class II DSA (p = 0.238). Anti-HLA DSA were not associated with graft failure (GF) in the cohort. There was no difference in relapse or acute or chronic GVHD in patients with and without DSA. Conclusion: Anti-HLA Class I DSA > 1000 MFI after haplo-HSCT was associated with lower OS and EFS and higher one-year mortality, but no with GF, acute or chronic GVHD, or relapse.