Objective To investigate the therapeutic efficacy of HLA-genotype matched platelet transfusion using a platelet donor database for severe platelet transfusion refractoriness (PTR) caused by HLA antigen-antibody incompatibility. Methods Using real-time quantitative PCR (qPCR) to identify he patient's HLA class I genotype, followed by searching the platelet donor database for matching donors, and selecting highly compatible donors for transfusion. Platelets with higher compatibility levels were prioritized for transfusion recommendations. Results Among the 19 patients studied, 7 patients identified donors with B2U or higher compatibility, 6 patients identified donors with BX or higher compatibility, and 6 patients did not find a suitable donor. The transfusion efficacy was evaluated by calculating the corrected count increment (CCI) 24 hours post-transfusion, and all transfusions were effective. Conclusion The optimal strategy to prevent and treat patients with severe platelet transfusion refractoriness is to ensure patients receive platelet transfusions that are matched to their HLA genes, and this approach significantly enhances transfusion efficacy.
Humans ; Platelet Transfusion/adverse effects* ; HLA Antigens/immunology* ; Male ; Middle Aged ; Female ; Adult ; Blood Platelets/immunology* ; Aged ; Genotype

Objective Analyze the human leukocyte antigen(HLA) class-I antibody specificity and antigenic determinants in patients with ineffective platelet transfusion, to provide theoretical basis for the establishment and application of platelet donor bank in Shandong Province. Methods 69 patients with ineffective platelet transfusion, the patients specimens were subjected to specific detection of HLA class-I antibody, and the possible antigenic determinants were analyzed using HLA Matchmaker software, and the relative immunogenicity of the antigen was calculated. Results A total of 113 specific antibodies were detected in 69 patient specimens. Among which 33 were antibodies to the HLA-A loci, with the highest frequency of HLA-A*69:01 (54%), 54 were antibodies to the HLA-B loci, and the highest frequency of HLA-B*15:12 (64%); 25 antibodies against Cw loci with low platelet expression were detected, with HLA-C*17:01 having the highest frequency (38%). Using HLA Matchmaker software, a total of 221 HLA class I epitopes were detected, among which 163LG and 163L had the highest probability, reaching 59.4%. Among the HLA-A loci, the allele HLA-A*02:03 has the highest relative immunogenicity at 137.157, while the allele HLA-A*02:05 has the lowest relative immunogenicity at 0.1450. In the HLA-B locus, the relative immunogenicity of HLA-B*73:01 allele is the highest, reaching 229.885, while the relative immunogenicity of HLA-B*13:02 allele is the lowest, reaching 0.121. Conclusion This study obtained the distribution characteristics of HLA class-I antibodies in PTR patients in Shandong population, providing theoretical basis for precise platelet transfusion, improving transfusion efficiency, and establishing and applying platelet supply banks.
Humans ; Platelet Transfusion ; Male ; Female ; Middle Aged ; Epitopes/genetics* ; China ; Adult ; Histocompatibility Antigens Class I/genetics* ; Antibodies/blood* ; Aged ; Young Adult ; HLA-A Antigens/genetics* ; Adolescent ; HLA-B Antigens/genetics*

OBJECTIVES: To study the clinical characteristics of pediatric Behçet syndrome (BS). METHODS: A retrospective review was conducted on the medical records of children hospitalized in the Department of Pediatrics at the Second Hospital of Hebei Medical University between December 2014 and December 2024 who met diagnostic criteria for BS. RESULTS: Among 45 children with BS, 26 (58%) were male. Oral aphthous ulcers were the most common manifestation (43/45, 96%), followed by genital ulcers (23/45, 51%) and gastrointestinal involvement (18/45, 40%). Genital ulcers were more frequent in girls, whereas ocular involvement was more common in boys (<i>Pi><0.05). The pathergy test was positive in 10 (22%), and HLA-B51 was positive in 13 (29%). Fecal calprotectin (FC) was elevated in 16 (36%); gastrointestinal involvement was more frequent in children with elevated FC than in those with normal FC (<i>Pi><0.05). According to the respective criteria, 17 (38%) patients met the International Study Group criteria (1990), 33 (73%) met the International Criteria for Behçet Disease (2014), and 13 (29%) met the Pediatric Behçet Disease criteria (2015). CONCLUSIONS Pediatric BS shows marked clinical heterogeneity. HLA-B51 is associated with disease susceptibility.
Humans ; Behcet Syndrome/genetics* ; Male ; Female ; Child ; Retrospective Studies ; Adolescent ; Child, Preschool ; Leukocyte L1 Antigen Complex/analysis* ; HLA-B51 Antigen

OBJECTIVE: To confirm the sequence of a null allele <i>HLA-C*08:127Ni> produced by a base insertion. METHODS: PCR sequence-specific oligonucleotide probe (SSOP) and PCR sequence-based typing (SBT) were used for HLA routine detection, which discovered abnormal sequence maps of <i>HLA-Ci> in one acute myeloid leukemia patient. The sequence of the above loci was confirmed by next generation sequencing (NGS) technology. RESULTS: The SSOP typing result showed that <i>HLA-Ci> locus was <i>C*03:04, C*08:01i>, while the sequence was suspected to be inserted or deleted in exon 3 by SBT, and finally confirmed by NGS as <i>C*03:04, C*08:127Ni>. CONCLUSION When base insertion produces HLA null alleles, SBT analysis software cannot provide correct results, but NGS technology can more intuitively obtain accurate HLA typing results.
Humans ; Alleles ; High-Throughput Nucleotide Sequencing ; HLA-C Antigens/genetics* ; Histocompatibility Testing ; Polymerase Chain Reaction ; Leukemia, Myeloid, Acute/genetics* ; Sequence Analysis, DNA ; Mutagenesis, Insertional ; Exons

OBJECTIVE: To distinguish the ambiguous genotyping results of human leukocyte antigen (HLA), identify a novel <i>HLA-Bi> allele and analyze the nucleotide sequence. METHODS: A total of 2 076 umbilical core blood samples from the Zhejiang Cord Blood Bank in 2022 were detected using the next generation sequencing technology (NGS) based on the Ion Torrent S5 platform. Among these a rare <i>HLA-Bi> allele with ambiguous combination result containing a base mutation was identified, and was further confimed by the third-generation sequencing (TGS) based on the nanopore technology. RESULTS: The NGS typing result of <i>HLA-Bi> locus showed <i>HLA-Bi>* 46:18, 54:06 or <i>HLA-Bi>*46:01, 54:XX (including a base mutation), and nanopore sequencing confirmed the typing as <i>HLA-Bi>*46:01, 54:XX (including a base mutation). Compared with <i>HLA-Bi>*54:01:01:01, the <i>HLA-Bi>*54:XX allele showed one single nucleotide substitution at position 1014 T>C in exon 6, with no amino acid change. The nucleotide sequence of the novel <i>HLA-Bi>*54:XX has been submitted to the GenBank nucleotide sequence database and the accession number OP853532 was assigned. CONCLUSION A ambiguous genotyping of the <i>HLA-Bi> Locus detected by NGS was distinguished by nanopore sequencing and a new <i>HLA-Bi> allele was successfully identified, which was officially named as <i>HLA-Bi>*54:01:11 by the World Health Organization Nomenclature Committee for Factors of the HLA System.
Humans ; High-Throughput Nucleotide Sequencing ; Alleles ; HLA-B Antigens/genetics* ; Genotype ; Mutation ; Sequence Analysis, DNA ; Base Sequence

OBJECTIVES: The major histocompatibility complex class I chain-related gene A (<i>MICAi>), a component of the human leukocyte antigen (<i>HLAi>) gene complex, is involved in the pathogenesis of various diseases including cancers and autoimmune disorders. Rosacea, a chronic inflammatory skin disease with a complex pathogenesis, potentially influenced by genetic and autoimmune factors. This study aims to investigate the relationship among <i>MICAi> gene polymorphisms, single nucleotide polymorphisms (SNPs), and susceptibility to rosacea, thereby offering new insights into the disease mechanism. METHODS: Peripheral blood DNA samples were collected from 84 patients with rosacea (rosacea group) and 223 healthy volunteers (control group) who visited the Dermatology Outpatient Department of Xiangya Hospital of Central South University between November 2017 and November 2019. <i>MICAi> genotyping was performed using polymerase chain reaction-sequencing-based typing (PCR-SBT) and the next-generation sequencing (NGS), and the accuracy of the 2 methods was compared. The frequency distributions of <i>MICAi> alleles between the 2 groups were analyzed. Amino acid clustering and SNP site analyses were conducted to identify haplotype-linked SNPs and to classify MICA polymorphic variants. Distribution differences of these classifications between groups were also examined. RESULTS: Blood tests in rosacea patients showed mildly elevated, with no significant changes in lymphocyte counts. Both PCR-SBT and NGS accurately identified <i>MICAi> alleles. The most common alleles in the rosacea group were <i>MICA*010:01i>, <i>MICA*008:04i>, and <i>MICA*019:01i>. The frequencies of <i>MICA*002:01i> and <i>MICA*027i> were significantly lower in the rosacea group compared to controls (6.55% vs 18.16% and 1.19% vs 5.38%, respectively), while and <i>MICA*010:01i> were significantly higher (7.74% vs 3.36% and 31.55% vs 18.61%, respectively; all <i>Pi><0.05). Five short tandem repeat (STR) alleles were identified. Frequencies of <i>MICA-A4i> and <i>MICA-A9i> were lower in the rosacea group than in the control group (16.07% vs 23.32% and 7.74% vs 17.26%, respectively), whereas <i>MICA-A6i> was higher (10.12% vs 4.03%; all <i>Pi><0.05). Clustering and SNP analysis identified 6 linked SNP sites, classifying MICA variants into Type I (C₃₆+M₁₂₉+K₁₇₃+G₂₀₆+W₂₁₀+S₂₁₅) and Type II (Y₃₆+V₁₂₉+E₁₇₃+S₂₀₆+R₂₁₀+T₂₁₅). Type I MICA variants were significantly associated with rosacea susceptibility. CONCLUSIONS <i>MICAi> gene polymorphisms are associated with susceptibility to rosacea, and there are 6 linked SNP sites within the <i>MICAi> gene. Based on this, MICA polymorphic variants are classified into Type I and Type II, with Type I being more closely associated with disease development of rosacea.
Humans ; Polymorphism, Single Nucleotide ; Histocompatibility Antigens Class I/genetics* ; Rosacea/genetics* ; Genetic Predisposition to Disease/genetics* ; Female ; Male ; Adult ; Middle Aged ; Genotype ; Alleles ; Gene Frequency ; Haplotypes ; Case-Control Studies ; Aged ; High-Throughput Nucleotide Sequencing

OBJECTIVES: To investigate the mechanism by which transforming growth factor‑β (TGF‑β) regulates major histocompatibility complex class I (MHC-I) expression in hepatocellular carcinoma (HCC) cells and its role in immune evasion of HCC. METHODS: HCC cells treated with TGF‑β alone or in combination with SB-431542 (a TGF-β type I receptor inhibitor) were examined for changes in MHC-I expression using RT-qPCR and Western blotting. A RNA interference experiment was used to explore the role of miR-23a-3p/IRF1 signaling in TGF‑β‑mediated regulation of MHC-I. HCC cells with different treatments were co-cultured with human peripheral blood mononuclear cells (PBMCs), and the changes in HCC cell proliferation was assessed using CCK-8 and colony formation assays. T-cell cytotoxicity in the co-culture systems was assessed with lactate dehydrogenase (LDH) release and JC-1 mitochondrial membrane potential assays, and T-cell activation was evaluated by flow cytometric analysis of CD69 cells and ELISA for TNF-α secretion. RESULTS: TGF‑β treatment significantly suppressed MHC-I expression in HCC cells and reduced T-cell activation, leading to increased tumor cell proliferation and decreased HCC cell death in the co-culture systems. Mechanistically, TGF-β upregulated miR-23a-3p, which directly targeted IRF1 to inhibit MHC-I transcription. Overexpression of miR-23a-3p phenocopied TGF‑β‑induced suppression of IRF1 and MHC-I. CONCLUSIONS We reveal a novel immune escape mechanism of HCC, in which TGF‑β attenuates T cell-mediated antitumor immunity by suppressing MHC-I expression through the miR-23a-3p/IRF1 signaling axis.
Humans ; MicroRNAs/genetics* ; Carcinoma, Hepatocellular/metabolism* ; Liver Neoplasms/metabolism* ; Interferon Regulatory Factor-1/metabolism* ; Transforming Growth Factor beta/metabolism* ; Signal Transduction ; Histocompatibility Antigens Class I/metabolism* ; Cell Line, Tumor ; Tumor Escape ; Coculture Techniques

The Qa-1 in mice is homologous to human leukocyte antigen E(HLA-E), and both of them belong to the non-classical major histocompatibility complex I b(MHC-I b) molecules. Qa-1 is capable of presenting self or exogenous antigen peptides to interact with two distinct receptors, namely T cell receptor (TCR) and natural killer cell group 2 member A (or C) (NKG2A/C), thus playing an important role in immune response and regulation. Qa-1-restricted regulatory CD8⁺ T cell (CD8⁺ Treg) is one of the most studied CD8⁺ Treg subgroups, which can maintain immune homeostasis and autoimmune tolerance by exerting immunosuppressive effects. Consequently, Qa-1-restricted CD8⁺Treg cells are closely associated with the occurrence and development of various clinical diseases, such as tumors, infections, autoimmune diseases, and transplant rejections. This paper provides a comprehensive review of the phenotypic characteristics, functional effects, regulatory mechanisms of Qa-1-restricted CD8⁺ Treg cells, as well as the latest research progresses of Qa-1-restricted CD8⁺ Treg cells involved in the pathogenesis of infectious diseases.
Humans ; Animals ; T-Lymphocytes, Regulatory/immunology* ; Histocompatibility Antigens Class I/immunology* ; CD8-Positive T-Lymphocytes/immunology* ; Communicable Diseases/immunology*

BACKGROUND: Although the need for consolidation chemotherapy after successful induction therapy is well established in patients with acute myeloid leukemia (AML) in first complete remission (CR1), the value of consolidation chemotherapy before allogeneic hematopoietic stem cell transplantation remains controversial. METHODS: We retrospectively compared the effect of the number of pre-transplant consolidation chemotherapies on outcomes of human leukocyte antigen-matched sibling stem cell transplantation (MSDT) for patients with AML in CR1 in multicenters across China. In our study, we analyzed data of 373 AML patients in CR1 from three centers across China. RESULTS: With a median follow-up of 969 days, patients with ≥ 3 courses of consolidation chemotherapy had higher probabilities of leukemia-free survival (LFS) (85.6% vs . 67.0%, P < 0.001) and overall survival (89.2% vs . 78.5%, P  = 0.007), and better cumulative incidences of relapse (10.5% vs . 19.6%, P  = 0.020) and non-relapse mortality (4.2% vs . 14.9%, P  = 0.001) than those with ≤ 2 courses of consolidation chemotherapy. Pre-transplantation minimal residual disease-negative patients with AML in CR1 who received MSDT with ≥ 3 courses of consolidation chemotherapy had a higher probability of LFS (85.9% vs . 67.7%, P  = 0.003) and a lower cumulative incidence of relapse (9.6% vs . 23.3%, P  = 0.013) than those with ≤ 2 courses. CONCLUSION Our results indicate that patients with AML in CR1 who received MSDT might benefit from pre-transplant consolidation chemotherapy.
Humans ; Retrospective Studies ; Consolidation Chemotherapy/methods* ; Siblings ; Hematopoietic Stem Cell Transplantation/methods* ; Leukemia, Myeloid, Acute/etiology* ; HLA Antigens ; Allografts

Objective To identify the potential long non-coding RNA (lncRNA) expressed in rheumatoid arthritis (RA) synovium key to RA onset and investigate its association with immune cell infiltration. Methods RA synovium data were downloaded from the GEO database and normalized. The lncRNAs key to RA onset were identified using multiple machine learning methods. Infiltration of 22 immune cell populations in RA synovium was measured by cell-type identification by estimating relative subsets of RNA transcripts (CIBER-SORT). The relationship between the key lncRNA and infiltrating immune cells was analyzed. Finally, real-time quantitative PCR was applied to validate the expression of the key lncRNA in RA synovial cells. Results lncRNA human leukocyte antigen complex P5(HCP5) was identified as the key lncRNA associated with RA onset. Infiltration analysis revealed increased abundance of CD8⁺ T cells, γδ T cells, and M1 macrophages while decreased abundance of M2 macrophages in RA synovial tissue. Correlation analysis demonstrated that the lncRNA HCP5 expression was positively associated with the infiltration abundance of CD8⁺ T cells, γδ T cells, and M1 macrophages in RA synovial tissue. Furthermore,the expression of lncRNA HCP5 in RA synovial cells was up-regulated. Conclusion lncRNA HCP5 expression is up-regulated in RA synovial tissue and potentially associated with immune cells infiltration.
Humans ; Arthritis, Rheumatoid ; CD8-Positive T-Lymphocytes ; HLA Antigens/metabolism* ; RNA, Long Noncoding/metabolism* ; Synovial Membrane/metabolism*