International Journal of Immunogenetics最新文献

The strong linkage between HLA-DRB1*15:03 and DRB5*01:01 is well established globally, yet its expression patterns in Saudi donors remain underexplored. In this study, we analysed high-resolution HLA genotypes derived from next-generation sequencing of 28,927 stem cell donors of Saudi ethnicity registered in the Saudi Stem Cell Donor Registry. We identified carriers of DRB1*15:03 and recorded their DRB5 status. Descriptive statistics were used to summarise allele frequencies and haplotype configurations. We found DRB1*15:03 in 931 donors (3.22%). Of these, 926 individuals (99.46%) co-expressed DRB5*01:01, four (0.43%) carried DRB5*02:02 and one (0.11%) had no detectable DRB5 alleles. This study indicates a nearly universal linkage disequilibrium between DRB1*15:03 and DRB5*01:01 in the Saudi population, with the absence of DRB5 being infrequent. These findings confirm the infrequency of DRB5 absence and the importance of complete DRB3/4/5 typing to optimise donor matching and minimise immunogenic risk.

The etiology of ankylosing spondylitis (AS) is complex and not yet fully understood. Interleukin-6 (IL-6), vitamin D and the vitamin D receptor (VDR) play an important role in modulating immune response, and Torque teno virus is considered a marker of immune status. This case-control study aimed to investigate the predisposition to AS. A total of 85 patients with AS and 100 clinically healthy individuals were included. VDR polymorphisms (rs2228570, rs1544410, rs7975232, rs731236) were genotyped using the PCR-RFLP technique, while for the IL-6 -174 G>C (rs1800795) polymorphism the tetra-primer ARMS-PCR technique was used. The presence of TTV was detected using the hemi-nested PCR technique. Our findings indicate a statistically significant association between TTV and AS (p = 0.035). C allele of both rs1800795 polymorphism in main groups (p = 0.027) and rs731236 polymorphism in women subgroups (p = 0.036) may be linked to an increased susceptibility to AS. However, none of these associations reach statistical significance after Bonferroni correction. Furthermore, within female subgroups, a significant association was found between the T allele of rs1544410 polymorphism and AS (p = 0.000038, corrected p = 0.00076). A significant association was also observed between the TT genotype of rs2228570 polymorphism, TTV and AS (p = 0.029). Haplotype analysis revealed that certain VDR haplotypes may confer either a protective effect against AS or an increased risk of developing the condition. Notably, rs1544410 polymorphism or a linked polymorphism may influence AS susceptibility. In conclusion, our data suggest that TTV and VDR polymorphisms may be associated with an increased risk of developing AS, indicating that these markers could potentially be used in the future for earlier diagnosis and more targeted treatment of the disease.

Antibodies directed to mismatched donor human leucocyte antigen (HLA-DSA) play a well-established role in antibody mediated rejection (AMR) and graft failure in kidney transplantation, with their presence being correlated with poorer transplant outcomes. The diagnosis of AMR is based on three criteria: Histologic evidence of acute tissue injury, evidence of current/recent antibody interaction with the donor endothelium and serologic evidence of circulating donor-specific antibody (DSA), HLA and non-HLA. Whilst there is significant evidence around the role of HLA-DSA, there is limited evidence of the role of the latter and the elucidation of these targets is still in its infancy, but it is clear that these may play a significant role in the immune response to a transplanted organ. This literature review aims to summarise what is currently known about the role of non-HLA antibody in renal transplantation.

Peri-implantitis is a pathological condition occurring in tissues around dental implants. This study aims to analyse the effect of TGF-β1 rs1800470 polymorphism on peri-implantitis. A total of 160 patients with implants without peri-implantitis and 160 patients with peri-implantitis were recruited from the clinic for this study. The genotype of TGF-β1 rs1800470 and TGF-β1 expression were detected by TaqMan-qPCR and RT-qPCR, respectively. Distributions of genotypes and allele frequencies were analysed by the chi-square test. A Hardy-Weinberg equilibrium (HWE) test was performed to detect whether the gene distribution was established. The diagnostic value of TGF-β1 for peri-implantitis was analysed by the ROC curve. TGF-β1 expression was significantly lower in peri-implantitis patients, which has diagnostic significance for peri-implantitis. TGF-β1 rs1800470 genotypic distribution conformed to the Hardy-Weinberg equilibrium test. CT and TT genotypes were significantly correlated with the development of peri-implantitis (p = 0.004, OR = 2.107, 95% CI = 1.259-3.527). CT and TT genotypes were validated as causative genotypes for peri-implantitis. Polymorphisms at the TGF-β1 rs1800470 locus have an impact on the development of peri-implantitis, and CT and TT genotypes increase the risk of developing peri-implantitis.

The MYH9 gene encodes the heavy chain of non-muscle myosin IIA (NMIIA), which converts chemical energy into mechanical energy and provides power for the contraction of the actin cytoskeleton. This is necessary for many important physiological processes such as cell morphology maintenance, migration, adhesion, division and individual development. Patients with autosomal dominant genetic diseases caused by MYH9 mutation show macrothrombocytopenia and complications such as renal failure, deafness and cataracts. However, in recent years, more and more studies have found that the activity of NMIIA is also related to various other diseases, including cancer, neurological diseases and infectious disorders. This article introduces the characteristics of myosin superfamily members and systematically reviews the structure, regulation and physiological functions of MYH9 and NMIIA, as well as MYH9-related disorders (MYH9-RD) caused by MYH9 mutations, focusing on the role of NMIIA in the pathogenesis of various cancers, and summarizes the therapeutic mechanisms of its targeted drugs. Besides, the effects of NMIIA in neurological diseases and infectious diseases are discussed to provide a comprehensive theoretical basis and insights for MYH9 and NMIIA as a therapeutic target for multiple diseases.

This meta-analysis aims to evaluate the association between interleukin-10 (IL-10) -819 C/T (rs1800871), -592 C/A (rs1800872) and -1082 A/G (rs1800896) polymorphisms and leprosy susceptibility by analyzing multiple genetic models in the Asian and Caucasian populations. A systematic literature search was conducted in PubMed, Web of Science, Google Scholar and Embase (January 2001 to February 2025) following PRISMA guidelines. Case-control studies reporting genotype distributions for IL-10 polymorphisms in leprosy cases and controls were included. Pooled odds ratios (ORs) and 95% confidence intervals (CIs) were calculated under allelic, recessive, dominant and over-dominant models. Heterogeneity was assessed using Cochran's Q test and the I² statistic. Publication bias was evaluated using Egger's test and funnel plots. A total of 13 studies were included, comprising 5509 leprosy cases and 8135 controls. The -1082 A/G variant exhibited a significant protective effect across allelic (A vs. G OR = 0.73, 95% CI 0.59-0.91, p = 0.005), dominant (AA+AG vs. GG OR = 0.45, 95% CI 0.25-0.80, p = 0.006) and the over-dominant models (AG vs. AA+ GG OR = 0.45, 95% CI 0.25-0.80, p = 0.006). Under the dominant model, the -819 C/T (CC+CT vs. TT OR = 0.76, 95% CI 0.61-0.96, p = 0.02) and -592 C/A (CC+CA vs. AA OR = 0.71, 95% CI 0.52-0.97, p = 0.03) polymorphisms also showed significant protective effects, suggesting a potential role of heterozygosity in reducing leprosy susceptibility. Subgroup analysis indicated stronger protective effects in Asians. Power analysis confirmed that the included studies had sufficient sample sizes to detect significant associations (α error probability < 0.05). This meta-analysis supports the protective role of IL-10 polymorphisms, particularly the -1082 A (rs1800896) allele, in reducing leprosy susceptibility. These findings underscore the role of genetic variation in disease susceptibility and suggest that IL-10 polymorphisms could serve as biomarkers for leprosy susceptibility.

Preeclampsia (PE) is a major pregnancy complication with considerable maternal and fetal morbidities. The recent evidence indicates that immunological factors have critical roles in PE pathogenesis. This study assessed the association between genetic variations in IL-35 components, specifically IL-12A (rs568408) and EBI3 (rs4740) polymorphisms, and PE susceptibility in an Iranian population. A case-control study with 470 participants was carried out, and polymorphism detection was achieved by the PCR-RFLP technique. Genetic analysis revealed distinct associations between IL-35 components polymorphisms and PE risk. For IL-12A rs568408, the AA mutant genotype significantly increased PE susceptibility (OR = 3.350, p = 0.007), with stronger associations in severe PE cases (OR = 5.048, p < 0.001). Similarly, the mutant allele showed risky effects in total group and severe subgroup (OR = 1.743, p = 0.001; OR = 2.307, p < 0.001). The EBI3 rs4740 polymorphism analysis showed that AA genotype carriers had a protective effect (OR = 0.495, p = 0.036), particularly noticeable in severe cases (OR = 0.409, p = 0.037). In addition, the mutant allele demonstrated protective effects in the total PE, severe and particularly in early-onset manifestations (OR = 0.651, OR = 0.559, OR = 0.478, respectively). Combined genotype analysis showed that IL-12A AA/EBI3 GA carriers had the highest risk of severe, early-onset PE (OR = 5.280, p = 0.046, OR = 5.945, p = 0.038). This study provides a better understanding of the causes of PE and points out possible genetic markers to be used in its risk assessment.

Background/objectives: The human major histocompatibility complex (MHC) is characterized by extreme polymorphism, with HLA-C contributing to pathogen defence, disease susceptibility, and transplantation outcomes. Beyond allelic diversity, and variation, the evolutionary restructuring of haplotypes influences functional diversity across the region. This study analysed HLA-C haplotypes in the context of transposable element (TE) architecture and single-nucleotide polymorphism (SNP) patterns to identify conserved modules and ancestral recombination boundaries.

Methods: Paired genomic alignments of fully phased homozygous lymphoblastoid cell lines carrying 36 haplotypes of HLA-C*01-C*07, C*12, and C*16 allelic groups were performed using Mauve to define locally co-linear blocks. SNP density plots were generated to visualize transitions between SNP-rich and SNP-poor regions. Six diverse HLA-C*07 haplotypes (linked to HLA-B*07, *08, *18, *49, *57 and *58) were examined as a primary case study. Particular focus was placed on crossover zones where SNP transitions coincided with TE boundaries, indicating putative ancestral recombination breakpoints.

Results: Comparative analyses revealed extensive structural variation among C*07 haplotypes and across the broader C*01-C*16 series. The C*07:02 homologs exhibited significantly higher SNP density (mean = 1.87 ± 0.44 SNPs/kb, n = 10) than C*07:01 and C*07:18 homologs (mean = 0.29 ± 0.21 SNPs/kb, n = 20; p < 0.001). Abrupt SNP transitions frequently aligned with SINE, LINE, and LTR elements (e.g., Alu, L1, L2, HERV), marking recurrent TE-associated junctions. These breakpoints defined shared homozygous HLA-C segments spanning ∼4 kb to ∼4 Mb, consistent with mosaic haplotype evolution through recombination of conserved modules.

Conclusions: HLA-C haplotypes exhibit modular mosaic structures shaped by recurrent recombination at TE-associated crossover zones. Thus, MHC haplotypes may share the same HLA-C allele, yet differ in the surrounding HLA-B and class I genomic organization, preserving or disrupting co-adapted functional units. Incorporating haplotypic mosaicism, rather than focusing solely on allelic polymorphism, may improve models of immune variation, disease risk, and translation matching.