Antibody-mediated rejection (AMR) is a serious post-transplant complication that is associated with a worse prognosis of survival of transplanted organs. The diagnosis of AMR is based on clinical, pathological characteristics and on the detection of antibodies specific to the organ donors' mismatched human leukocyte antigens (HLA) antigens. Accumulating evidence in recent years however suggests that antibodies against antigens encoded by genes outside the HLA complex can play a role in the development of AMR. Non-HLA antigens are mostly expressed on the surface of endothelial and epithelial cells but can also be localized intracellularly and released in the bloodstream or lymph in case of cell lysis. Among these are major histocompatibility complex (MHC) Class I-related chain MICA, MICB, angiotensin II-R1 receptor (ATR1), collagen, K-α1 tubulin, cardiac myosin, vimentin and other molecules. Antibodies to non-HLA antigens can occur before transplantation but may be also produced de novo. The detection of non-HLA antibodies is carried out using the xMap (Luminex) technology, the so-called endothelial crossmatch and other techniques; however, these methodologies and interpretation of results have their pitfalls. In this short review, we briefly discuss the recent literature on the clinical role of non-HLA antibodies in organ transplant rejection and survival.
The Saudi stem cell donor registry (SSCDR) has successfully recruited over 92,000 unrelated potential stem cell donors through nationwide campaigns. The Western region of Saudi Arabia is characterized by its unique ethnic diversity, shaped by centuries of immigration and pilgrimage. This study aimed to determine the distribution of HLA alleles and haplotypes among donors from this region. A total of 1112 donors registered with SSCDR were included, all recruited during campaigns conducted in the Western region between 2019 and 2021. Participants provided ancestry information to confirm their city of origin. High-resolution HLA typing for loci A, B, C, DRB1 and DQB1 was performed using sequence-based typing (SBT). Allele and haplotype frequencies were estimated for each subgroup using Arlequin 3.5 software. Distinct haplotype patterns were observed across cities. The most common haplotypes in the 1112 potential stem cell donors in the Western Region of Saudi Arabia were HLA-A*02:01∼C*07:02∼B*07:02∼DRB1*15:01∼DQB1*06:02 and HLA-A*02:01∼C*06:02∼B*50:01∼DRB1*07:01∼DQB1*02:01 in Jeddah; A*23:01∼C*06:02∼B*50:01∼DRB1*07:01∼DQB1*02:01 in Al-Madinah; HLA-A*26:01∼C*07:02∼B*08:01∼DRB1*03:01∼DQB1*02:01, HLA-A*30:01∼C*06:02∼B*13:02∼DRB1*07:01∼DQB1*02:01 and HLA-A*02:01∼C*06:02∼B*50:01∼DRB1*07:01∼DQB1*02:01 in Makkah; HLA-A*02:01∼C*15:02∼B*51:01∼DRB1*13:01∼DQB1*06:03 and HLA-A*02:01∼C*07:02∼B*07:02∼DRB1*15:01∼DQB1*06:02 in Al-Baha; and HLA-A*31:01∼C*15:02∼B*51:01∼DRB1*13:01∼DQB1*06:03 in Taif. HLA data are available in the Allele Frequencies Net Database (AFND: 3854, 3855, 3856, 3857 and 3858) under the population name 'Saudi Western Region'. In western Saudi Arabia, HLA allele and haplotype distributions demonstrate marked city-specific variation. Our research identifies DR7-, DR13- and DR15-based haplotypes as the most prevalent across the region. These findings are critical for optimizing unrelated donor searches for patients lacking compatible familial matches. Understanding these local frequencies allows for more targeted recruitment and better matching probabilities in stem cell registries.
There is considerable variability in the clinical presentation of COVID-19 among patients infected with SARS-CoV-2. Genome-wide association studies (GWASs) have identified the 12q24.13 and 3p21.31 regions, derived from Neanderthal DNA, as the human genetic loci most strongly associated with COVID-19 severity. We examined in this study the 3p locus in the Moroccan population by analysing allele and haplotype frequencies at the LZTFL1 gene and their associations with COVID-19 outcomes. Three SNPs at LZTFL1, tagging the Neanderthal-derived COVID-19 risk haplotype, were sequenced by Sanger's method in 102 ambulatory participants and 105 hospitalized patients and have been compared to 118 controls negative for SARS-CoV-2 infection using logistic regression analysis. Results showed that the prevalence of the lead variant rs11385942 in this locus was 8.9%, whereas the variants rs35044562 and rs13078854, which tag the Neanderthal haplotype, were present in only 6.3%. Our study showed that only the rs35044562-T and rs13078854-A alleles were associated with a 2.5-fold increased risk of severe COVID-19 (p = 0.028). These two alleles, in LD with the rs11385942-AA one, form the haplotype inherited from the Neanderthal, the only haplotype associated with COVID-19 severity in the Moroccan population (p = 0.030), whereas sub-Saharan African and the rare local haplotype also containing the rs11385942 variant do not influence the COVID-19 outcomes 19 (p > 0.05). Furthermore, our study showed that the Neanderthal haplotype at 3p21 locus exists in the inhabitants of Morocco at a frequency close to that of Europeans and suggests a close connection between North Africa and Eurasia.
Prior studies have shown that donor-derived cell-free DNA (dd-cfDNA) predicts renal biopsy-defined transplant rejection with a high negative predictive value (NPV). However, these studies were not in UK-based cohorts. The KORAD study aimed to assess relationships between dd-cfDNA levels and biopsy-defined rejection in a UK kidney transplant cohort, along with relationships with DSA and creatinine levels. dd-cfDNA was determined using AlloSeq cfDNA (CareDx) and DSA was identified with LABScreen single-antigen beads (Thermo Fisher Scientific). Eighty samples from 78 transplant patients had concomitant dd-cfDNA, DSA and creatinine results. The median percentage of dd-cfDNA in plasma samples with concomitant DSA negative results was significantly less than in DSA positive samples (0.37% vs. 3.15%, p = 0.002). There was no significant difference in the median percentage of dd-cfDNA in plasma samples with concomitant samples with elevated creatinine levels (0.41% vs. 0.36%, p = 0.779). Thirty-nine of these plasma samples had concomitant renal biopsy results. Thirty-two biopsies were negative for rejection and seven were positive for rejection. A receiver operating characteristic curve analysis showed that dd-cfDNA levels distinguished biopsy-defined rejection from no rejection with an acceptable AUC of 0.737 (95% CI, 0.485-0.987). The %dd-cfDNA threshold maximising overall correct classification was 0.7%. Using this threshold might have prevented 26 patients from undergoing renal biopsy unnecessarily, with two patients directed not to have a biopsy incorrectly (26 dd-cfDNA values being true negatives and two false negatives; NPV: 93% (95% CI, 83%-100%)), which outperformed the NPV for DSA: 88% (95% CI, 77%-99%) and creatinine 85% (95% CI, 69%-100%). We showed that the optimal dd-cfDNA threshold (0.7%) in this study was lower than the 1% threshold identified in non-UK studies. AlloSeq cfDNA (CareDx) with the optimal threshold showed an acceptable level of discrimination of biopsy-proven rejection and a potential to reduce the number of biopsies performed.
Systemic lupus erythematosus (SLE) is a multifactorial autoimmune disease in which genetic and environmental factors play important role in SLE pathogenesis. Recently, cytoplasmic phosphatidylinositol transfer protein 1 (PITPNC1) was reported to be capable of enhancing vesicular secretion, which was correlated with autoimmune disorders contributing to SLE. Here, we aimed to explore the genetic association between PITPNC1 polymorphisms and SLE susceptibility. The genetic association analysis included two cohorts: a discovery cohort (490 SLE cases vs. 493 healthy controls) and replication cohort (1003 SLE cases and 815 healthy controls). rSNPBASE, RegulomeDB databases, and Three-dimensional (3D) chromatin looping data were used for functional annotation, and luciferase reporter assay was performed for validation. The expression data from ArrayExpress were used for PITPNC1 gene expression analysis. Three variants (rs4239092, p = 3.04×10-2; rs6504516, p = 3×10-2; rs2706682, p = 3.88×10-4) were significantly associated with the increased susceptibility to SLE in a previous GWAS cohort. The prominent rs2706682 was successfully replicated (p = 1.44×10-3), and the significance of genetic association was reinforced reaching 6.21×10-6 (OR 2.36, 95% CI 1.63-3.42). Functional analysis showed that rs2706682 is a regulatory SNP located within the strong transcription and enhancer chromatin state region. Further, dual-luciferase reporter gene assay demonstrated that the risk G allele correlated with increased expression. Finally, the gene expression analysis showed that the level of PITPNC1 expression was significantly higher in patients with SLE. Our study identified that the variant rs2706682 in PITPNC1, encoding an important player in enhancing extracellular vesicles, was associated with SLE susceptibility.
Analytical ambiguity is an inherent and expected feature of reverse sequence-specific oligonucleotide (rSSO)-based HLA genotyping and reflects the size of the candidate allele space compatible with a given probe pattern at the analytical interpretation level. However, ambiguity is often treated as a binary attribute, which may obscure differences in its magnitude across platforms. We conducted a between-subject comparison of two commercial rSSO HLA typing platforms, One Lambda (386 patients; 6176 allele-level observations) and Immucor GTI (1003 patients; 16,048 allele-level observations). Analytical ambiguity was quantified as candidate allele count (CandidateCount) across eight HLA loci (A, B, C, DRB1, DQB1, DQA1, DPB1 and DPA1). Generalized estimating equations with a negative binomial family were used to account for within-patient clustering, with rate ratios estimated using Immucor GTI as the reference and p-values adjusted for multiple testing. Four loci showed significantly larger analytical candidate allele spaces on One Lambda than on Immucor GTI after Benjamini-Hochberg correction, with the largest effect observed at DPA1, where mean CandidateCount values were more than doubled (18.3 vs. 8.3). Moderate but significant differences were also observed at HLA-A, DQB1 and DPB1, whereas no significant platform differences were detected at HLA-B, HLA-C, DRB1 or DQA1. These findings demonstrate that analytical ambiguity differs between commercial rSSO HLA typing platforms in a locus-specific manner. Quantitative characterization of ambiguity at the raw interpretation level may help set expectations regarding locus-specific resolution burden and support workflow planning in laboratories using rSSO as a first-line typing approach.
The use of umbilical cord blood (UCB) as a stem cell source in haematopoietic stem cell transplant (HSCT) has greatly declined in recent years. It has largely been replaced by mismatched unrelated and family donors, facilitated by advances in transplant technologies, including post-transplant cyclophosphamide to prevent graft-versus-host disease (GVHD). UCB remains a distinctive source of haematopoietic stem cells (HSCs) with unique immunologic and practical advantages, including for those with malignant and non-malignant diseases. Compared to other cell sources, UCB transplantation (UCBT) offers comparable survival with reduced chronic GVHD (cGVHD) and with a potent graft-versus-leukaemia (GVL) effect. These outcomes likely reflect the biology of cord-derived lymphocytes-particularly naïve, adaptable CD8+ T-cells capable of rapid differentiation and tumour-directed cytotoxicity without sustained alloreactivity. UCB permits greater human leukocyte antigen (HLA) mismatch tolerance, especially when transplant is performed T-cell replete and can be accessed immediately, reducing time to transplant for high-risk leukaemia. In addition, recent advances in ex vivo expansion technologies have overcome historical limitations of low cell dose and delayed engraftment, expanding UCB's applicability to older paediatric and adult recipients. This review discusses the evidence of using UCB as a preferred stem cell source in patients with relapsed/refractory haematological malignancies and how we may interrogate the properties of UCB to improve outcomes in these high-risk cohorts.
Human leucocyte antigen (HLA) class I and human platelet antigens (HPAs) can elicit immune responses, leading to platelet transfusion refractoriness (PTRs). To support the clinical management of patients with PTR, transfusion of HLA class I and sometimes HPA-selected apheresis platelets is recommended. To facilitate this service, the HLA class I and HPA genotypes of platelet donors must be defined so that appropriate platelet units may be selected. Currently, National Health Service Blood and Transplant (NHSBT) utilises two separate assays for genotyping HLA class I and HPAs. In this study, a simple, single-well, multiplex PCR assay has been developed to genotype classical HLA class I genes (HLA-A, -B and -C) and 27/35 currently described HPAs, including all clinically relevant HPAs. Genomic DNA from 90 consented English apheresis platelet donors and 17 reference samples provided by the Australian Red Cross were amplified with the custom PCR protocol. Sequencing libraries were prepared using Oxford Nanopore Technologies (ONTs) native barcoding kit v14 (SQK-NBD114.96) and sequenced on MinION R10.4.1 flow cell. Base calling was performed live in MinKNOW v24.02.16, and sequence alignment, variant calling and genotype assignment of HPA were performed by a bespoke bioinformatics pipeline. Analysis of HLA class I genes was carried out using NGSengine v4.0.0. English apheresis platelet donors successfully genotyped (89/90) using the described assay showed 100% concordance with historic results for both HLA and clinically relevant HPAs. Further testing with reference samples from the Australian Red Cross samples showed 100% concordance with externally provided HPA results. This assay offers a simplified workflow for simultaneous HLA class I and HPA genotyping of apheresis platelet donors, permitting automation and significant expansion to include more HPA specificities. This assay provides accurate HLA class I genotyping and HPA genotyping in a single assay, requiring a minimal laboratory footprint and less maintenance than current in-use assays.
The study aims to investigate the expression characteristics and functions of miR-148a-3p in atopic dermatitis (AD), as well as its association with inflammation. A total of 150 skin tissue samples from patients with AD and 146 samples from healthy individuals were collected in this study. The expression level of miR-148a-3p was detected by RT-qPCR. An in vitro inflammatory model was established by treating HaCaT cells with TNF-α/IFN-γ. Cell proliferation and apoptosis were detected by the CCK-8 assay and flow cytometry, respectively. The levels of inflammatory factors were detected by ELISA and RT-qPCR. The targeting relationship between miR-148a-3p and PTEN was verified by dual-luciferase reporter assay. The expression of miR-148a-3p was significantly upregulated in the skin tissues of patients with AD and in TNF-α/IFN-γ-treated HaCaT cells. Inhibition of miR-148a-3p could promote cell proliferation, inhibit apoptosis, and significantly reduce the expression of inflammatory factors. PTEN was identified as a direct target of miR-148a-3p. Knockdown of PTEN reversed the protective effect of miR-148a-3p inhibitor on HaCaT cells. Under the context of AD, miR-148a-3p promotes the maintenance of inflammation and cell apoptosis in epidermal keratinocytes by inhibiting PTEN, which may exacerbate the disruption of the skin barrier.
Celiac disease (CD) risk conferred by HLA-DQ2 and DQ8 varies significantly across populations. In north India, where CD is as prevalent as in European populations, reports on the association of HLA-DQ2 and DQ8 with CD are limited. In a north Indian CD case-control cohort (459 CD and 450 controls), known CD-associated risk HLA-DQ alleles, HLA-DQA1*05:01/02:01/03:01 and HLA-DQB1*02/*03:02, were genotyped using SSP-PCR to uncover their frequency and association with CD. Published dense Illumina_Immunochip genotyping data of the study cohort were used to identify proxy-SNPs for HLA-DQ genotypes and their alleles. We also investigated the correlation between common CD phenotypes and DQ2/8 genotypes. Ninety-nine percent of the CD patients were found to carry HLA-DQ2.5, DQ2.2 or 8. HLA-DQA1*05:01 (OR = 5.86 [4.39-7.81], p < 0.0001) and HLA-DQB1*02 (OR = 16.61 [11.37-24.25], p < 0.0001) were identified as the strongest susceptibility alleles. HLA-DQ2.5 was present in 92% of patients and conferred the highest CD risk (OR = 29.01 [19.56-43.00], p < 0.00001), while DQ8 appeared protective (OR = 0.42 [0.25-0.70], p < 0.0001). HLA-DQ2.5/8 and HLA-DQ2.5/2.2 were found significantly associated with serum anti-tTG-IgA and skin conditions, respectively, among CD patients. rs1129740, rs9273012 and rs7744001 were identified as proxy-SNPs to efficiently predict the presence/absence of DQ2.5, DQ2.2, DQ8 and its alleles. This was the first well-powered study to evaluate the susceptibility of HLA-DQ in CD among the north Indian population. HLA-DQ2.5 showed a strong association with CD, conferring a higher disease risk, while DQ8 appeared protective, and the contribution of DQ2.2 was inconclusive. Three proxy-SNPs, rs1129740, rs9273012 and rs7744001, could be utilized to predict HLA-DQ genotypes as a cost-effective alternative for CD risk assessment.
INTRODUCTION:Accurate HLA allele identification is essential to ensure graft-recipient compatibility. Advances in next-generation sequencing (NGS), such as those provided by Illumina and Oxford Nanopore Technologies, have improved resolution of HLA-typing. METHODS AND RESULTS:Here, a novel HLA-C*12 allele with a silent mutation (G to A) was identified in a bone marrow donor homozygous for HLA-C*12. The allele was initially linked to HLA-C*12:03:01 by short-read NGS, but further investigation by long-read sequencing revealed the mutation to be associated with HLA-C*12:02:02. Phasing limitations of short-read NGS made accurate allele assignment difficult, but precise differentiation became possible with longer reads. The origin of the mutation was subsequently confirmed by sequencing parental samples. CONCLUSION:This case highlights the ability of long-read sequencing to resolve cis-trans ambiguities and improve allele phasing, and to enhance accuracy for new HLA allele identification.
Pancreatic beta cell destruction in Type 1 diabetes (T1D) is a possible consequence of an intricate autoimmune crosstalk between environmental factors and genetic elements. The vitamin D receptor (VDR) gene apart from regulating insulin secretion from the pancreas, also functions as a mediator of immune response through vitamin D. These interplay mechanisms vary across studies and population groups. Therefore, the aim of this study is to explore the association between VDR gene polymorphisms and T1D among South Indian subjects. This was a single-centre, prospective, case-control study that included 150 T1D and 155 non-diabetic control participants. All the participants' blood samples were analysed for vitamin D levels. TaqMan real-time assays were used to analyse the FokI (rs2228570), BsmI (rs1544410) and TaqI (rs731236) polymorphisms. The levels of vitamin D were significantly lower in the T1D group than in the control group. A statistically significant variation in the genotype of VDR polymorphism BsmI was noted between T1D and controls, with the homozygous variant (AA) of BsmI rs 1544410 present more frequently in the T1D group (44%) compared to the control group (23.2%) (odds ratio [OR] = 2.265, 95% confidence interval [CI]: 1.380-3.719, p < 0.001). The frequency of the A allele of the BsmI polymorphism was also significantly higher in the T1D (p < 0.002). Analysis of haplotype showed that combinations T-A-T and C-A-T were statistically linked with susceptibility to T1D (p < 0.008 and p < 0.005, respectively). High linkage disequilibrium (LD) was found between TaqI and BsmI (D' = 0.71). Statistically significant differences were not encountered in genotype and allelic frequencies of VDR polymorphism of either FokI or TaqI. This study findings revealed that BsmI polymorphism in the VDR gene and particular haplotypes are possibly associated with susceptibility to T1D in the South Indian population.
Multiple sclerosis (MS) is a chronic central nervous system inflammatory disease of autoimmune aetiology. The disease is mostly considered due to a complex interaction between different genetic and environmental factors. DNA methylation is an epigenetic mechanism that can influence gene expression and has the potential to mediate the effects of environmental factors on MS. This study aimed to identify MS risk methylation haplotypes (meplotypes) and their associated genes by integrating epigenome-wide meplotype association analysis with gene optimisation. We conducted the first epigenome-wide meplotype association study for MS using methylation data from peripheral blood lymphocytes (PBLs) of 140 MS patients and 139 normal controls. The analytical procedure comprised the following steps: (1) conversion of DNA methylation level into menotypes; (2) identification of methylation disequilibrium (MD) block and performance of meplotype association analysis; (3) screening of risk meplotypes and their mapping to genes; (4) conducting functional analysis of the candidate genes; and (5) final identification of MS risk genes through gene optimisation. Our analysis identified 286 meplotypes across 191 MD blocks that were significantly associated with MS (p value < 0.05). Of these, 120 meplotypes were found to confer increased risk for MS susceptibility and were mapped to 134 candidate genes. Gene optimisation identified four MS risk meplotypes on three key genes: HLA-DQA1, HLA-DRB5 and HLA-DRB1. These results not only confirm the pivotal role of HLA-DRB1 in MS but also report, for the first time, an association between MS and DNA methylation patterns in HLA-DQA1 and HLA-DRB5. This study demonstrates that epigenome-wide methylation haplotype analysis offers a powerful and novel perspective for identifying MS-related genes.
Systemic lupus erythematosus (SLE) is a heterogeneous autoimmune disorder influenced by genetic and environmental factors. Vitamin D deficiency and vitamin D receptor (VDR) gene polymorphisms are suggested to modulate immune dysregulation in SLE. This study aimed to investigate the association of VDR polymorphisms (BsmI, ApaI, TaqI and FokI), serum 25-hydroxyvitamin D [25-OH vitamin D] levels and clinical phenotypes in Indian SLE patients. A hospital-based case-control study was conducted on clinically diagnosed SLE patients (n = 297) fulfilling American College of Rheumatology (ACR) criteria and healthy controls (n = 100). Serum 25-OH vitamin D levels, autoantibody profile and complement components were evaluated by immunofluorescence, enzyme-linked immunosorbent assay (ELISA) and nephelometry. Genotyping for VDR polymorphisms BsmI (rs1544410) B/b, ApaI (rs7975232) A/a, TaqI (rs731236) T/t and FokI (rs2228570) F/f was performed using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Data were statistically analysed using chi-square tests, logistic regression and correlation analysis. The median age at evaluation in SLE patients was 29 years, with a female predominance (91.9%). Median serum 25-OH vitamin D levels were 30.4 ng/mL, with lower levels observed in patients with arthritis (p = 0.012), neurological involvement (p = 0.015) and active disease (p = 0.025). Serum 25-OH vitamin D inversely correlated with disease activity (r = -0.127, p = 0.032), anti-cardiolipin antibody (ACLA) immunoglobulin G (IgG) (p < 0.001) and anti-phospholipid antibody (APLA) IgG (p = 0.030). Among VDR polymorphisms, BsmI b allele conferred reduced disease risk (odds ratio [OR] = 1.85, p < 0.001). TaqI genotypes (Tt: OR = 2.29 and tt: OR = 6.48, p < 0.05) and t allele (OR = 2.15, p < 0.001) and FokI genotypes (Ff: OR = 4.13 and ff: OR = 3.14, p <0.05) were strongly associated with increased susceptibility to SLE. ApaI variants were significantly associated with alopecia, haematological manifestations, disease activity and low complement component 3 (C3) levels, whereas BsmI and FokI polymorphisms were associated with neurological manifestations (p < 0.05). Vitamin D receptor gene (VDR gene) polymorphisms may contribute to phenotypic variability and immune dysregulation in Indian SLE patients, suggesting that gene-environment interactions between vitamin D status and VDR variants may influence SLE susceptibility and clinical heterogeneity.
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.
