We evaluated blood group typing in a cohort of deceased organ donors comparing serological and genotyping methodologies. Our objectives were to determine the frequency and characteristics of serological discrepancies, assess concordance between phenotypic and genotypic results, and determine the utility of genotyping in resolving typing challenges in both the pre- and post-transfusion settings. Specimens from over forty-four thousand deceased donors were collected by Organ Procurement Organizations and submitted for STAT testing. Gel column agglutination or test tube method was performed for serological typing. Genotyping was performed on 471 donors using real-time PCR. Serologic ABO typing results were indeterminate in 4% of samples. ABO genotyping demonstrated high concordance with serologic typing in evaluable cases and successfully resolved many otherwise indeterminate donor evaluations. ABO genotyping is a reliable adjunct to serologic testing in deceased donor evaluation and provides value in transfused donors and cases with serologic ambiguity. Integration of genotyping methods into donor testing workflows may improve the safety, accuracy, and efficiency of organ allocation practices.

The human leukocyte antigen (HLA) system is the most polymorphic gene complex in the human genome and plays a central role in susceptibility to autoimmune disease and drug hypersensitivity. HLA typing tools arcasHLA, T1K, HLA-HD and OptiType each emit a distinct output, creating a manual reformatting bottleneck. We present HLAnte, a Python command-line interface that parses all four formats, normalizes calls against a version-pinned IPD-IMGT/HLA database, and consolidates GWAS Catalog, PharmGKB, Clinical Pharmacogenetics Implementation Consortium (CPIC), and Allele Frequency Net Database (AFND) evidence in one provenance-tagged report. Across 2692 samples from the 1000 Genomes Project, parse rates were 99.8-99.9% and HLAnte matched 26,300 of 26,301 calls to an IPD-IMGT/HLA name; that is coverage, not specificity: only 0.75% of calls resolve to a single allele. We quantified annotation-retrieval fidelity, not clinical detection: CPIC Level 1A retrieval was 100% for four sentinel allele-drug pairs and disease-annotation retrieval 99.7-100% across seven allele-disease pairs. AFND coverage (the proportion of annotated calls with a population allele-frequency record for the sample's super-population) was 99.8-100% in every super-population with the full AFND snapshot. Three worked examples illustrate use: pharmacogenomic triage, population-referenced frequency reporting, and cohort disease-association screening. HLAnte is available under the MIT license (https://github.com/efe3506/HLAnte).

The human leukocyte antigen (HLA) allele and haplotype frequencies were calculated from 263,542 voluntary donors with medium- to high-resolution typing. This is the first study of a large sample with high-resolution HLA typing in the Thai population. The total numbers of two-field single alleles for HLA-A, -B, -C, -DRB1, and -DQB1 were 139, 198, 115, 80, and 24, respectively. The proportion of each HLA allele in Thais ranged from 1.54% to 3.45% of the total two-field HLA alleles in the IPD-IMGT/HLA database. The frequencies of alleles following common, intermediate, and well-documented (CIWD) groups for HLA-A, -B, -C,-DRB1, and -DQB1 were 69, 123, 55, 69, and 18, respectively. The CIWD percentages were 49.64%, 62.12%, 47.83%, 86.25%, and 75.0%, respectively. The alleles with a frequency greater than 5% were A*02:03, A*02:07, A*11:01, A*24:02, A*33:03, B*13:01, B*15:02, B*40:01, B*46:01, B*58:01, C*01:02, C*03:02, C*03:04, C*07:01, C*07:02, C*08:01, DRB1*03:01, DRB1*04:05, DRB1*07:01, DRB1*09:01, DRB1*12:02, DRB1*15:01, DRB1*15:02, DRB1*16:02, DQB1*02:01, DQB1*03:01, DQB1*03:02, DQB1*03:03, DQB1*05:01, DQB1*05:02, and DQB1*06:01. The haplotypes with a frequency greater than 2% were A*02:07 ∼ C*01:02 ∼ B*46:01 ∼ DRB1*09:01 ∼ DQB1*03:03, A*11:01 ∼ C*08:01 ∼ B*15:02 ∼ DRB1*12:02 ∼ DQB1*03:01, A*33:03 ∼ C*03:02 ∼ B*58:01 ∼ DRB1*03:01 ∼ DQB1*02:01,and A*33:03 ∼ C*07:01 ∼ B*44:03 ∼ DRB1*07:01 ∼ DQB1*02:01. These findings enable the registry to predict the opportunity to find well-matched organ and stem cell donors for patients with rare HLA typing.

Pro-inflammatory macrophage cell death is essential for resolving inflammation, yet the subtype-specific mechanisms governing this cell death remained unclear. Herein, THP-1-derived macrophages were polarized into pro-inflammatory (M1) or anti-inflammatory (M2) subtypes and exposed to lipopolysaccharide. M1 cells exhibited higher DNA fragmentation, caspase-3 cleavage, and lactate dehydrogenase release. Pharmacologic inhibition or genetic knockdown of caspase-2 effectively attenuated LPS-triggered M1 macrophage cell death. Mechanistic analyses excluded contributions of the mitochondrial apoptotic pathway, as no Bid cleavage, mitochondrial membrane potential dissipation, or rescue effect of cyclosporin A were detected. IFN-γ pretreatment enhanced caspase-8 cleavage, while caspase-2 deficiency consistently blocked caspase-8 activation under diverse death stimuli: LPS, etoposide, tumor necrosis factor-related apoptosis-inducing ligand, and hydrogen peroxide. IFN-γ priming alone triggered caspase-2 cleavage without inducing cell death, and this pre-activated caspase-2 pool strongly amplified subsequent LPS-mediated caspase-8 activation. Collectively, our work identifies a non-canonical, mitochondria-independent caspase-2/caspase-8 axis that selectively drives LPS-induced cell death in IFN-γ-primed THP-1 macrophages. This pathway acts as a self-regulatory feedback loop to eliminate hyper-inflammatory macrophages and maintain immune homeostasis, providing a novel mechanistic framework for understanding subtype-specific macrophage cell death.

Alopecia areata (AA) is a relapsing autoimmune disease characterized by non-scarring loss of hair following the collapse of immune privilege of the anagen hair follicles. This review summarizes recent molecular findings linking follicular stress to an atypical cytotoxic response, with special emphasis on the role of CD8 + NKG2D+ T cells, stress-induced ligands (MICA/ULBPs), and a Th1 cytokine circuit triggered by IFN-γ and IL-15, which communicates via the JAK/STAT pathway. We present new evidence that oxidative stress and mitochondrial dysfunction can enhance immune activation and may follow disease activity, generating the prospect of redox- and mitophagy-based adjunctive interventions. In addition to mechanisms, we discuss genetic susceptibility loci and high-throughput profiling, such as transcriptomics and proteomics, and describe how integrated multi-omics can be used to assist endotyping, prognostication, and biomarker-sensitive treatment selection. In treatment, AA is moving toward narrow-based agents rather than general immunosuppression and local agents. The efficacy standard is now set by JAK inhibitors, with baricitinib supported by landmark phase 3 studies demonstrating significantly increased scalp regrowth compared to placebo, and newer selective JAK inhibitors and IL-15-based or other immune checkpoint biologics are under development. Combination regimens based on immune signature, real-world safety surveillance, and strategies to achieve long-term immune tolerance and reestablish follicular immune privilege over short-term suppression are the key priorities in the future.

Human leukocyte antigen matched unrelated donor (URD) identification remains a major challenge for Indian patients due to high genetic diversity and endogamy. Utilizing a HLA high-resolution dataset of 30,027 umbilical cord blood (UCB) units, this study modeled 10/10 and 8/8 matching probabilities for five broad regions and nine sub-regional linguistic populations. Two statistical frameworks, the Formula Matching Method (FMM) and the Actual Measurement Method (AMM) were used to project match rates for registry sizes ranging from 5000 to 1000,000 donors. Using FMM, the probability of identifying a 10/10 and 8/8 matched donor in sub-regional cohorts was approximately 25% at a registry size of 30,000 and increased substantially with larger registry size, reaching approximately 40% at a registry size of 100,000. By relaxing the matching criteria to 9/10 or 7/8, 50% match probability was achieved with a registry size of 30,000. Conversely, AMM produced more conservative estimates, highlighting the effect of stochastic sampling and registry composition. Importantly, significant regional disparities were observed, with highly diverse populations requiring disproportionately larger registries. These findings are highly relevant for determining the optimal national registry size and planning a geographically targeted recruitment by prioritizing highly diverse regions.

Epidermal growth factor receptor (EGFR) is overexpressed in more than 90% of head and neck squamous cell carcinoma (HNSCC) cases and plays a critical role in tumor progression, metastasis, and therapeutic resistance, making it an attractive target for immunotherapy. This study aimed to design and comprehensively evaluate a multi-epitope peptide vaccine targeting the extracellular domain of EGFR using an integrated immunoinformatics approach. Linear B-cell, helper T lymphocyte (HTL), and cytotoxic T lymphocyte (CTL) epitopes were predicted and screened for antigenicity, immunogenicity, allergenicity, toxicity, HLA binding affinity, population coverage, and IFN-γ induction. Selected epitopes were assembled into a multi-epitope vaccine construct and evaluated through structural modeling, molecular docking, molecular dynamics simulation, immune simulation, and codon optimization. Epitope conservancy was assessed across reviewed EGFR isoforms, followed by structural and HNSCC somatic mutation mapping. The vaccine construct exhibited favorable antigenic, non-allergenic, and non-toxic properties with broad predicted population coverage. Among the HTL epitopes, CQGTSNKLTQLGTFE was predicted to induce IFN-γ. Molecular docking and dynamics simulations demonstrated stable receptor interactions, whereas immune simulation predicted robust humoral and cellular immune responses. Six of the ten selected epitopes were completely conserved across all reviewed EGFR isoforms, while the remaining epitopes retained 75% conservancy. Importantly, none of the recurrent extracellular EGFR mutations identified in 619 profiled HNSCC tumors overlapped with the selected epitopes. These findings support the proposed EGFR-targeted multi-epitope vaccine as a promising immunotherapeutic candidate for HNSCC and provide a strong computational foundation for future experimental validation.

To characterize the clinical and immunological features of DOCK8 deficiency and better define its disease spectrum, we retrospectively analyzed 11 patients diagnosed at our hospital between 2014 and 2025. All patients presented in early childhood, most commonly with eczema and recurrent infections, and a higher rate of Epstein-Barr virus infection. Severe systemic infections, including sepsis and purulent meningitis, were observed in two patients at disease onset. Multisystem involvement was identified, including gastrointestinal, urinary, and cardiovascular abnormalities. Immunological evaluation showed reduced CD3[+] and CD4[+] T cells, decreased naïve T cells, and increased terminal effector memory T cells (TEMRA), which progressively accumulated during disease course. Eight patients underwent hematopoietic stem cell transplantation (HSCT): five achieved favorable outcomes, while three experienced severe complications, leading to two deaths. These findings indicate that DOCK8 deficiency is characterized by allergic manifestations, recurrent infections, and multisystem involvement, likely related to T-cell dysfunction. Early recognition and genetic diagnosis may facilitate timely consideration of HSCT and improve clinical outcomes.