BACKGROUND: In KhMAO-Yugra, every year there is an increase in the number of cases of type 1 diabetes mellitus (DM1) among residents of the district. The preservation of small indigenous peoples is an important demographic problem that requires an integrated approach. HLA-typing makes it possible to identify genetic markers of predisposition to type 1 diabetes mellitus (DM1) in the early stages of the disease and to ensure its prevention.AIM: Identification of the frequency of carriage of polymorphic alleles and haplotypes in the loci of the HLA-DQA1, HLA-DQB1 and HLA-DRB1 genes of the HLA class II system in samples of the indigenous khanty population and the alien population permanently residing in the territory of KhMAO-Yugra.MATERIALS AND METHODS. Low-resolution HLA typing was performed in 60 representatives of the khanty indigenous people, 54 conditionally healthy people of the alien population and 45 patients with type 1 diabetes mellitus (alien population) permanently residing in the territory of the Khanty-Mansiysk Autonomous Okrug.RESULTS: The analysis of the frequency of occurrence of class II HLA alleles in the khanty cohort revealed statistically significant differences in the alleles DQA1*01:02/03; DQB1*02; *03:02; *05:02/04; *06:01; *06:02-8; DRB1*03; *04; *12; *13; *15; *16 in comparison with the cohort of the conditionally healthy alien population. A similar comparison of the frequencies of DQA1, DQB1, DRB1 alleles, haplotypes and their combinations between representatives of the alien population of conditionally healthy and patients with DM1 revealed significant differences in loci DQA1*01:02/03; *03:01; DQB1*06:02-8; DRB1*07, characteristic of Caucasians. When comparing the frequencies of haplotypes in Hunts with a cohort of conditionally healthy newcomers, a statistically significant low frequency of haplotypes associated with a high and moderate risk of developing DM1 (DR4~DQ8, DR3~DQ2) and a high frequency of «protective» haplotypes DQ6~DR15, DQ6~DR13 were noted.CONCLUSION: In the khanty cohort, the frequency of occurrence of three haplotypes predisposing to the development of DM1 was reduced, and two protective haplotypes were increased, in comparison with the cohort of a conditionally healthy alien population. This determines the significant role of genetic factors in the observed low predisposition to the development of type 1 diabetes in the khanty population.

BackgroundGestational diabetes mellitus (GDM) is an endocrine disorder that occurs easily in women during pregnancy. HLA-DQA1/DQB1 genes play a crucial role in the regulation of the human immune and endocrine systems, potentially influencing the pathogenesis of GDM.ObjectiveTo explore the associations between single nucleotide polymorphisms (SNPs) in HLA-DQA1/DQB1 genes and the risk of GDM.MethodsSeven functional SNPs of HLA-DQA1/DQB1 genes were selected and genotyped in 523 GDM patients and 638 normal pregnant women. The odds ratio (OR) and its corresponding 95% confidence interval (CI) were utilized to assess the association between candidate SNPs and the risk of GDM. And then, false positive report probability (FPRP), multifactor dimensionality reduction (MDR) and haplotype analysis were employed to validate the statistically significant associations between studied SNPs and GDM risk.ResultsCompared to those with 0–1 risk genotypes, individuals with 2–7 unfavorable genotypes presented an increased risk of GDM (adjusted OR = 1.54, 95% CI=1.04-2.28, P=0.033). A dose- accumulation effect was detected between the number of unfavorable genotypes and GDM risk (Ptrend=0.024). Furthermore, stratified analysis revealed that the increased GDM risk was more likely to occur in individuals with higher blood pressure and TG, and lower HDL-c levels (P<0.05). Multifactor dimensionality reduction (MDR) analysis revealed that rs9274666 was the best single locus model, whereas the 7-loci model was the best multifactor interaction model for predicting GDM risk (χ²=134.28, P<0.0001). Finally, haplotype analysis revealed that the ACGAGTA and ACGGATA haplotypes were significantly associated with the increased GDM risk. HLA-DQA1/DQB1 SNPs can significantly alter individuals’ genetic susceptibility to GDM.ConclusionsThe genetic variations in the HLA-DQA1 and HLA-DQB1 genes may collectively contribute to the susceptibility to gestational diabetes mellitus. These findings suggest that these genetic markers could be useful for early prediction of GDM, and further validation in larger cohorts is warranted.

HLA allelic polymorphisms are associated with a variety of kidney-related traits in different populations. Although Taiwanese-specific genetic variants associated with kidney function have been reported, the role of HLA alleles is unclear. In this study, the associationbetween eGFR and genetic variations in the HLA region was explored in a cohort of 59,448 Taiwanese subjects. A total of 448 genetic variations in the HLA region are significantly associated with eGFR. HLA-C*03 is associated with decreased eGFR, while HLA-DQA1*03, HLA-DQB1*03:03 and HLA-DQB1*03:03:02 demonstrated protective effects. Moreover, amino acid changes on HLA-C and HLA-DRB1 are significantly associated with eGFR. Finally, the eGFR-associated single nucleotide variations (SNVs) and insertions and deletions (indels) are enriched in the HLA-DQB1 gene. After conditional analysis, we identified two independent signals, including rs2853941, rs3830060. In summary, this study highlights the role of HLA-C, HLA-DQA1, HLA-DQB1 and HLA-DRB1 variations in kidney function in the Taiwan Han Chinese population.

Abstract Introduction Narcolepsy is an uncommon sleep disorder characterized by excessive daytime sleepiness, cataplexy, hypnagogic hallucinations, sleep paralysis, low levels of hypocretin-1 in the CSF, and a strong association with the HLA DQB1*0602 allele. Secondary narcolepsy has been associated with infections including Streptococcus Pyogenes, COVID-19, influenza H1N1 and the H1N1 vaccination. To date, there is one reported case of narcolepsy type 1 (NT1) associated with M. Pneumonia infection in a pediatric patient. We report a case of narcolepsy type 2 (NT2) following M. pneumonia infection in an adult. Report of case A 33-year-old female with a history of severe persistent asthma, obesity, depression and PTSD who presented to sleep clinic with excessive daytime sleepiness for the past 8 months. She was initially hospitalized for an asthma exacerbation and found to have positive mycoplasma pneumonia IgM antibodies. Two weeks after discharge, she reports increased sleep requirements of 20 hours per day, auditory hypnogogic hallucinations, and infrequent episodes of sleep paralysis. Two months before her clinic visit, she fell asleep while driving, causing a motor vehicle accident. She denied symptoms of cataplexy. Her ESS was 19. Given an unremarkable physical exam, cranial imaging was deferred. Overnight polysomnogram showed positional sleep apnea with an overall AHI of 7. The five naps MSLT showed mean sleep latency of 4.4 minutes, 2 SOREMs, and negative urine drug screen. HLA DQB1*0602 was positive but she declined CSF analysis for hypocretin levels. She was treated with Modafinil 200 mg twice daily. However, due to persistent sleepiness she is awaiting approval to start Pitolisant. Conclusion NT1 is believed to be autoimmune mediated given the strong genetic association with HLA DQB1*0602 which regulates T-cell immunity. Several articles have reported the development of NT1 following infections, especially streptococcal infections, influenza, and most recently, COVID-19. This case highlights the development of NT2 following mycoplasma pneumonia infection and suggests a similar pathophysiology mechanism resulting in a partial loss of hypocretin producing cells. The hypothesized mechanisms include cytokine storm, hyper-activation of the immune system and molecular mimicry. Support (if any)

Abstract Introduction Efficient screening methods with high specificity which can be applied to large sample sizes are needed to improve significantly underdiagnosed people with narcolepsy type 1 (NT1). To address this unmet need, we combined polygenetic risk scores (PRS), HLA typing, and nocturnal polysomnography (PSG) data. These methods are developed and validated using a dataset significantly larger than those used in previous studies, ensuring their reliability and generalizability. Methods People with diagnosed narcolepsy were studied across 7 different global locations, involving multiple collaborators (coauthors limited by guidelines). We developed a custom U-Sleep model for variable-resolution sleep staging using electroencephalography, electrooculography, and electromyography data from 19,381 PSG recordings from the National Sleep Research Resource and the Stanford Sleep Clinic. Sleep staging was performed across epochs from 0.25 to 3600 seconds, leveraging novel multiscale transition matrix (MTM) features to capture NT1-specific transitions and overlapping sleep stages. Next, a Gaussian processes classifier was trained on features from 21,846 PSGs across 14 cohorts (NT1: n=327; controls: n=21519) and tested on 634 separate PSGs (NT1: n=317; controls: n=317). An ensemble model combined multiple time resolutions, weighted by prediction accuracy. Classifier performance was evaluated using 5-fold cross-validation. We developed a multi-information model integrating new PRS scores with HLA DQB1*06:02 typing, where HLA- and PRS+ conditions map to control and NT1 prediction, respectively, with PSG used when neither applies. Results Adding PRS to HLA increased the specificity from 81.9% to 100.0%, with a sensitivity of 25.9%, enabling potential screening of NT1 using genetics alone. When combining PSG with HLA, our approach yielded 99.4% specificity and 94.6% sensitivity, surpassing State-of-the-Art (SOTA). Adding PRS further rescued HLA+ cases missed based off PSG, and increased sensitivity to 95.9% while maintaining 99.4% specificity. MTM features meaningfully boosted classification performance (approximately 1% gain) compared to SOTA features, which themselves significantly outperformed standard clinical PSG measures. Ensemble models showed that combining multiple resolutions improved performance, notably specificity. Additionally, post-hoc analyses show that genetic information noticeably improved model robustness. Conclusion These findings suggest that the proposed multimodal model is a robust framework for NT1 classification, providing more specific and sensitive screening methods. Support (if any) Funded by Takeda Development Center Americas, Inc.

Background. Celiac Disease (CD) is an autoimmune disorder triggered by gluten ingestion, leading to small intestine damage and potential malnutrition. CD has a strong genetic basis, primarily linked to specific Human Leukocyte Antigen (HLA) gene variants, especially HLA-DQ2 and HLA-DQ8, essential in presenting gluten peptides to immune cells. Objective. The study aims to evaluate the molecular detection of HLA-DQA1, HLA-DQB1, and Tissue Transglutaminase (TGM2) genes by using conventional PCR technique with specific primers in CD patients. Additionally, DNA sequencing of these genes was performed to compare them with standard genes to detect Single Nucleotide Polymorphisms (SNPs) occurring in the studied genes. Methodology. This study used a case-control design with 118 total participants, of whom 68 were newly diagnosed CD patients, while 50 comprised the control group. Participants were recruited from various teaching hospitals in Al-Basrah, Iraq, from December 2023 to June 2024. Fifteen samples were analyzed, with five for each primer used for DNA sequencing. PCR and Sanger sequencing were performed to detect genetic polymorphisms, and the novel DNA sequences were aligned with the NCBI reference sequences to verify the presence of SNPs. Results. The study identified ten SNPs in the HLA-DQA1 gene, one SNP in the HLA-DQB1 gene, and four SNPs in the TGM2 gene. These SNPs exhibited different zygosity states, with HLA-DQA1 showing both homozygous and heterozygous forms. Conclusion. The dbSNP database confirmed these detected polymorphisms, enhancing the understanding of genetic variation in CD-associated genes. This research supports the necessity of genetic testing for identifying CD predisposition and contributes to further genomic and clinical investigations of autoimmune diseases.

The co-infection of tuberculosis (TB) and human immunodeficiency virus (HIV) poses a major global health challenge. Human leukocyte antigen (HLA) plays a significant role in influencing the outcome of the disease. Several studies have revealed that HLA class II genes, specifically HLA-DRB1 and HLA-DQB1, are linked to TB and HIV infections. Only a few studies have investigated the genotype or allelic frequencies of HLA genes in the co-infection of HIV/TB. In this study, the mRNA expression of DRB1*15:01:01, DQB1*06:02:01:01, CD4, and IFNγ was determined in participants with mono-infection of HIV-1 (n = 28), mono-infection of TB (n = 31), and co-infection of HIV-1/TB (n = 21) and compared with healthy controls (n = 20). The relative quantification of the transcripts was determined using an RT2-Profiler PCR array. The findings revealed a significantly higher expression of the HLA-DRB1 gene, with a fold change of 3.7 (p = 0.005), in individuals with TB infection alone. In contrast, expression of the HLA-DQB1 gene was significantly decreased by 1.3-fold change (p = 0.008) in individuals with HIV-1/TB co-infection. Additionally, the mRNA expression of CD4 was elevated (fc: 1.2, p = 0.94) in the TB group, whereas in the HIV-1 and HIV-1/TB groups, there was a decrease in CD4 mRNA expression (HIV: fc −1.3, p = 0.045) (HIV-1/TB: fc −1.15, p = 0.191). In contrast, IFNγ mRNA expression was decreased in TB but relatively higher in individuals with HIV-1 and HIV-1/TB co-infection. We further evaluated the correlation between CD4 and IFNγ mRNA expression in all three groups. We found a significant negative correlation (TB: r = −0.386, HIV-1: r = −0.498, p &lt; 0.05) between CD4 and IFNγ in the TB and HIV-1 groups, while a positive correlation was observed in the HIV-1/TB group (r = 0.330, p &gt; 0.05). A decrease in HLA-DQB1 and CD4 mRNA expression and an increase in IFNγ in HIV/TB co-infection suggests that these markers are involved in the immunopathogenesis and progression of the disease.

Although numerous candidate genes have been identified in studies investigating the role of genetics in sarcoidosis, the strongest association has been reported with the Major Histocompatibility Complex/Human Leucocyte Antigen (MHC/HLA) region. This study aimed to evaluate HLA polymorphism and assess its association with cardiac and other extrapulmonary involvement in sarcoidosis patients. The study included 67 patients diagnosed with sarcoidosis. A control group of 100 bone marrow donors, who had undergone HLA genotyping previously, was also included. Blood samples were collected from all participants for HLA gene polymorphism analysis. The differences in HLA genotypes were investigated between patients with and without cardiac and other extrapulmonary involvement, and between these groups and the control group. Cardiac involvement, was present in 17.9% of the patients. The most frequently affected extrapulmonary organ was the skin (23.8%). HLA DQB103 and HLA DQB106 alleles were expressed more frequently in patients with only pulmonary involvement compared to those with extrapulmonary involvement. Conversely, HLA DQA101 was expressed more frequently in patients with extrapulmonary involvement. No statistically significant difference in the expression of HLA DRB1, HLA DQB1, and HLA DQA1 alleles was observed between sarcoidosis patients with and without cardiac involvement. Our findings suggest that HLA DQB103 and HLA DQB106 alleles might be protective against extrapulmonary organ involvement, while HLA DQA101 could be a risk factor. These findings may contribute to the prediction of treatment response and prognosis in sarcoidosis patients.

Multiple sclerosis (MS) is an inflammatory autoimmune disease affecting the central nervous system (CNS). The pathogenesis of MS is characterized by neuronal axonal degeneration and demyelination. Among the genes that raises MS risk are the HLA-class II genes. The goals of this study were to investigate the role of the HLA-DRB1 and HLA-DQB1 genes (for the first time) in Jordanian MS patients and their association with MS disease. The association of these genes with other clinical features, such as optic neuritis, sensory impairment, and brainstem symptoms in MS patients was investigated as well using PCR-SSP techniques. Our findings indicated an association between HLA-DRB1 * 03:01 (Pc = 0.01) and HLA-DRB1 * 04:01 (Pc = 0.004) alleles with Jordanian MS patients. In addition, a significant linkage between HLA-DRB1 * 15:01 and HLA-DQB1 * 06:01 alleles (Pc ≤ 0.001 and Pc = 0.012, respectively) were presented among Jordanian MS patients with optic neuritis compared to Jordanian MS patients without optic neuritis. Moreover, HLA-DQB1 * 05:01 and HLA-DQB1 * 06:02 alleles (Pc ≤ 0.001 and Pc = 0.006, respectively) was found to be related with sensory impairment in MS patients. Additionally, HLA-DRB1 * 07:01 allele indicates a positive correlation in MS patients with brainstem symptoms (Pc < 0.001). Moreover, our results indicated that there is no association on the HLA-DRB1 ~ HLA-DQB1 haplotype level and MS disease. Knowing the genes that are linked to MS, they may facilitate MS diagnosis, prevention, and treatment at earlier stage. Also, these results may serve in the development of more potent therapeutic regimens for MS and its related complications, such as optic neuritis, sensory impairment, and brainstem symptoms.

Endometriosis is a complex disease with diverse etiologies, including hormonal, immunological, and environmental factors; however, its exact pathogenesis remains unknown. While surgical approaches are the diagnostic and therapeutic gold standard, identifying endometriosis-associated genes is a crucial first step. Five endometriosis-related gene expression studies were selected from the available datasets. Approximately, 14,167 genes common to these 5 datasets were analyzed for differential expression. Meta-analyses utilized fold-change values and standard errors obtained from each analysis, with the binomial and continuous datasets contributing to endometriosis presence and endometriosis severity meta-analysis, respectively. Approximately 160 genes showed significant results in both meta-analyses. For Bayesian analysis, endometriosis-related single nucleotide polymorphisms (SNPs), the human transcription factor catalog, uterine SNP-related gene expression, disease-gene databases, and interactome databases were utilized. Twenty-four genes, present in at least three or more databases, were identified. Network analysis based on Pearson's correlation coefficients revealed the HLA-DQB1 gene with both a high score in the Bayesian analysis and a central position in the network. Although ZNF24 had a lower score, it occupied a central position in the network, followed by other ZNF family members. Bayesian analysis identified genes with high confidence that could support discovering key diagnostic biomarkers and therapeutic targets for endometriosis.

The development of accessible and sensitive methods for mutations analysis leading to tumor and for evaluation of patients’ individual genetic characteristics is essential for molecular genetic studies both in clinical and epidemiological research. The Central Research Institute of Epidemiology has developed a set of techniques for the qualitative detection of germinal mutations and single nucleotide polymorphisms, as well as for the quantification of the mutant alleles of somatic mutations using pyrosequencing and real-time PCR. The methods allow identifying the most common mutations in the Russian Federation in the BRCA1, BRCA2, NBN, and CHEK2 genes, responsible for hereditary tumor syndromes, and polymorphisms in the TTC34, MIR146A, CYP1A1, MICA, PAX8, MTHFR, HLA-DQB1, and HLA-DQA1 genes associated with an increased risk of cervical cancer, and in genes involved in drug biotransformation. Quantitative methods are designed to determine somatic mutations in the BRAF, KRAS, HRAS, NRAS, JAK2, MPL and CALR genes in the solid tumors and in hematology. The developed set of scientific and diagnostic techniques is being employed for analysis of genetic polymorphisms and mutations in Russian population. Some of the techniques are available as reagent kits and are used in practice.

Diabetes mellitus (DM) is a complex and multifactorial metabolic disorder with a significant genetic component. The human leukocyte antigen (HLA) genes, specifically HLA-DQA1, HLA-DQB1, and HLA-DRB1, have been implicated in the susceptibility and pathogenesis of DM. This review delves into the intricate interplay of these HLA genes, seeking to unravel the genetic tapestry that contributes to the development and progression of diabetes. We begin by providing an overview of the HLA system and its critical role in immune regulation. Subsequently, we explore the current state of knowledge regarding the association between HLA-DQA1, HLA-DQB1, and HLADRB1 polymorphisms and susceptibility to both type 1 and type 2 diabetes. Emphasis is placed on recent advancements in genetic research methodologies, including genomewide association studies and next-generation sequencing, that have provided deeper insights into the genetic architecture of DM. The review also scrutinizes the functional implications of specific HLA alleles in modulating immune responses and the potential mechanisms by which they contribute to the autoimmune processes observed in type 1 diabetes. Additionally, we examine the role of HLA genes in the context of insulin resistance and beta-cell dysfunction in type 2 diabetes, shedding light on the shared and distinct genetic underpinnings of these two major forms of DM. Furthermore, we discuss the clinical implications of HLA genotyping in predicting disease risk, prognosis, and personalized treatment strategies. The integration of genetic information into clinical practice holds promise for precision medicine approaches in diabetes management.

Tick-borne encephalitis is a natural endemic disease which is widely spread in Russia. The purpose of the study was to determine clinical significance of HLA class II genes in tick-borne encephalitis. We observed 75 patients with tick-borne encephalitis admitted to the Kirov Hospital of Infectious Diseases and district hospitals over 2020-2023. Molecular typing of the HLA genes DRB1, DQA1 and DQB1 was carried out using PCR technique, with a set of commercial sequence-specific primers (“DNA-Technology”, Russian Federation). The febrile form of tick-borne encephalitis was noted in 41.3% of patients; focal, in 34.7%; meningeal, in 16.0%, inapparent, in 8% of cases. The comparison group for HLA DRB1 locus included 1528 practically healthy individuals from the same population. Comparison group for HLA DQA1 and DQB1 genes comprised 133 persons. The study has revealed a number of HLA class II genes, which are found significantly more often in TBE patients, rather than in control group (DRB1*1 (χ2 = 12.2; pc &lt; 0.01), DRB1*4 (χ2 = 6 .4; pc &lt; 0.05), DRB1*7 (χ2 = 11.7; pc &lt; 0.01), DRB1*8 (χ2 = 4.6; pc &lt; 0.05), DRB1*13 (χ2 = 7.7; pc &lt; 0.01), DRB1*15 (χ2 = 9.3; pc &lt; 0.01), DRB1*16 (χ2 = 14.3; pc &lt; 0.01), DQA1*0102 (χ2 = 7.6; pc &lt; 0.01), DQB1*0401-2 (χ2 = 3.9; pc &lt; 0.05), DQB1*0502-4 (χ2 = 8.1; pc &lt; 0.01). Among HLA class II haplotypes, the susceptibility to the development of tick-borne encephalitis was determined by the combinations DRB1*08-DQA1*0401-DQB1*401/402 (χ2 = 5.7; pc &lt; 0.05), DRB1*09-DQA1*0301- DQB1*303 (χ2 = 5.7; pc &lt; 0.05) and DRB1*16-DQA1*0102-DQB1*502 (χ2 = 7.4; pc &lt; 0.01). Carriage of the DRB1*15 gene was most risky for development of febrile form of tick-borne encephalitis, (χ2 = 7.8; pc &lt; 0.01; RR = 3.1). Occurrence of three-locus haplotypes DRB1*09-DQA1*0301-DQB1*303 (χ2 = 8.8; pc &lt; 0.01), and DRB1*16-DQA1*0102-DQB1*502 (χ2 = 5.0; pc &lt; 0.05) was associated with increased risk of developing a febrile form of TE by 14.5 and 10.9 times, respectively. In patients with meningeal form of EC, compared with healthy individuals, the gene variants DRB1*08 (χ2 = 12.9; pc &lt; 0.01), DQA1*401 (χ2 = 3.9; pc &lt; 0.05), DQB1*401/402 (χ2 = 9.1; pc &lt; 0.01) were significantly more common. The presence of a threelocus haplotype DRB1*16-DQA1*0102-DQB1*502 (χ2 = 10.9; pc &lt; 0.01) increases the risk of developing a focal TBE by 17.7 times. Thus, tick-borne encephalitis is associated with certain HLA class II alleles, which may be used as a prognostic criterion for development of different clinical forms of tick-borne encephalitis, or tick-borne encephalitis in general.

Introduction: Numerous studies have concentrated on specific populations to explore the extensive polymorphism of class I and II HLA genes. This genetic diversity is crucial for various applications, such as advancing transplantation immunology, understanding genetic population patterns, and uncovering the pathways of different diseases. Objective: The objective of the present study was to determine and analyse the frequencies of class I (HLA-A, HLA-B and, HLA-C), and class II (HLA-DRB1, and HLA-DQB1) genes in the North Indian population. Material and Methods: To achieve the objective of the study, buccal swab samples from 3648 individuals were collected. All these samples were subsequently tested for the HLA-A, HLA-B, HLA-C, HLA-DRB1, and HLA-DQB1 genes using the polymerase chain reaction (PCR) sequence-specific oligonucleotide probe (SSOP) typing method and typing result were analyzed to estimate class I and II allele frequencies. Results: In the present study, we have identified 16 different variants of HLA-A genes, 28 variants of HLA-B genes, 13 variations of HLA-C genes, 14 variants of HLA-DRB1 genes, and 6 variants of HLA-DQB1 genes. Furthermore, HLA-A*11, HLA-B*35, HLA-C*07, HLA-DRB1*15, and DQB1*06 were observed to be the most frequent alleles within the studied population. Discussion: The findings of the studied population highlights the variability exhibited by the HLA-A, HLA-B, HLA-C, HLA-DRB1, and HLA-DQB1 genes in the North Indian population. Additionally, this also highlights the importance of testing and understanding the prevalence of these specific HLA genes in these populations, which has a greater relevance in both hematopoietic stem cell and solid organ transplantation as well as disease association studies.

The Canary Islands inhabitants, a recently admixed population with significant North African genetic influence, has the highest incidence of childhood-onset type 1 diabetes (T1D) in Spain and one of the highest in Europe. HLA accounts for half of the genetic risk of T1D.AimsTo characterize the classical HLA-DRB1 and HLA-DQB1 alleles in children from Gran Canaria with and without T1D.MethodsWe analyzed classic HLA-DRB1 and HLA-DQB1 alleles in childhood-onset T1D patients (n = 309) and control children without T1D (n = 222) from the island of Gran Canaria. We also analyzed the presence or absence of aspartic acid at position 57 in the HLA-DQB1 gene and arginine at position 52 in the HLA-DQA1 gene. Genotyping of classical HLA-DQB1 and HLA-DRB1 alleles was performed at two-digit resolution using Luminex technology. The chi-square test (or Fisher's exact test) and odds ratio (OR) were computed to assess differences in allele and genotype frequencies between patients and controls. Logistic regression analysis was also used.ResultsMean age at diagnosis of T1D was 7.4 ± 3.6 years (46% female). Mean age of the controls was 7.6 ± 1.1 years (55% female). DRB1*03 (OR = 4.2; p = 2.13–13), DRB1*04 (OR = 6.6; p ≤ 2.00–16), DRB1* 07 (OR = 0.37; p = 9.73–06), DRB1*11 (OR = 0.17; p = 6.72–09), DRB1*12, DRB1*13 (OR = 0.38; p = 1.21–05), DRB1*14 (OR = 0.0; p = 0.0024), DRB1*15 (OR = 0.13; p = 7.78–07) and DRB1*16 (OR = 0.21; p = 0.003) exhibited significant differences in frequency between groups. Among the DQB1* alleles, DQB1*02 (OR: 2.3; p = 5.13–06), DQB1*03 (OR = 1.7; p = 1.89–03), DQB1*05 (OR = 0.64; p = 0.027) and DQB1*06 (OR = 0.19; p = 6.25–14) exhibited significant differences. A total of 58% of the studied HLA-DQB1 genes in our control population lacked aspartic acid at position 57.ConclusionsIn this population, the overall distributions of the HLA-DRB1 and HLA-DQB1 alleles are similar to those in other European populations. However, the frequency of the non-Asp-57 HLA-DQB1 molecules is greater than that in other populations with a lower incidence of T1D. Based on genetic, historical and epidemiological data, we propose that a common genetic background might help explain the elevated pediatric T1D incidence in the Canary Islands, North-Africa and middle eastern countries.

In this study, we aimed investigated the differential gene expression profiles of samples from uninfected individuals (control group) and study groups of asymptomatic human T-lymphotropic virus 1 (HTLV-1) carriers and patients with HTLV-1-associated myelopathy (HAM) by exploratory RNA sequencing (RNA-Seq) analysis. The gene expression profiles of individuals in the asymptomatic group were represented by 3 genes, most associated with cell cycle regulation. The gene expression profiles of individuals in the HAM group were represented by 12 genes, the majority of which are associated with the immune response. The HLA-A gene and the non-coding RNA LINC02470 were upregulated in the asymptomatic and HAM groups. The HLA-DQB1 and HLA-C genes were downregulated in the asymptomatic and HAM groups. In this pilot study, although limited in terms of methodological rigor, we showed differential gene expression profiles in different clinical groups of HTLV-1 infection. However, further studies are needed to confirm these findings.

BackgroundSince the beginning of the anti-COVID-19 vaccination campaign, it has become evident that vaccinated subjects exhibit considerable inter-individual variability in the response to the vaccine that could be partly explained by host genetic factors. A recent study reported that the immune response elicited by the Oxford-AstraZeneca vaccine in individuals from the United Kingdom was influenced by a specific allele of the human leukocyte antigen gene HLA-DQB1.MethodsWe carried out a genome-wide association study to investigate the genetic determinants of the antibody response to the Pfizer-BioNTech vaccine in an Italian cohort of 1351 subjects recruited in three centers. Linear regressions between normalized antibody levels and genotypes of more than 7 million variants was performed, using sex, age, centers, days between vaccination boost and serological test, and five principal components as covariates. We also analyzed the association between normalized antibody levels and 204 HLA alleles, with the same covariates as above.ResultsOur study confirms the involvement of the HLA locus and shows significant associations with variants in HLA-A, HLA-DQA1, and HLA-DQB1 genes. In particular, the HLA-A*03:01 allele is the most significantly associated with serum levels of anti-SARS-CoV-2 antibodies. Other alleles, from both major histocompatibility complex class I and II are significantly associated with antibody levels.ConclusionsThese results support the hypothesis that HLA genes modulate the response to Pfizer-BioNTech vaccine and highlight the need for genetic studies in diverse populations and for functional studies aimed to elucidate the relationship between HLA-A*03:01 and CD8+ cell response upon Pfizer-BioNTech vaccination.

Autoimmune thyroid diseases (AITD), particularly Hashimoto's thyroiditis (HT) and Basedow-Graves disease (BGD) are diseases of global public health concern, characterized by autoimmune attacks on the thyroid gland, leading to hypothyroidism in HT and hyperthyroidism in BGD. We conducted a study between 2019 and 2021 in northwestern Transylvania (Romania) on patients with HT and with BGD compared to the control group. The aim of the study was to investigate the correlations of HLA class II alleles with AITD by identifying potential genetic susceptibility factors such as HLA-DRB1 and HLA-DQB1 genes in patients diagnosed with HT and BGD. Various molecular biology methods, including SSP-PCR low-resolution and PCR-SSO were employed to analyze DNA samples from patients and control subjects. Our study revealed the influence of the HLA-DRB1*03/*16 genotype as a genetic susceptibility factor for HT, a similar influence regarding BGD being observed for the HLA-DRB1*03 allele group, DRB1*03/*16 genotype, and the DRB1*03/DQB1*06 haplotype. The only protective factor detected in our study was the HLA-DRB1*13 allele group, for both HT and BGD. By elucidating any specific allele or genotype associations that might contribute to the development of AITD, our study can contribute to the prevention and early detection of these diseases.

The recurrence of idiopathic membranous nephropathy (iMN) after kidney transplantation is common, although its exact clinical significance remains unclear. This systematic review aims to elucidate the effects of iMN recurrence on graft survival. A literature search was performed by systematically searching Medline, Scopus, Web of Science, and Google Scholar from inception. Cohort studies examining iMN recurrence after kidney transplantation were deemed eligible. Meta-analysis was performed by fitting random-effects models. Twelve (12) articles published from 1995 to 2016 reporting on 139 transplant patients with recurrent iMN were included. The median time of the diagnosis of recurrent iMN was 18 months during follow-up from 35 to 120 months. Risk factors for iMN recurrence in the renal allograft are a positive serum test for anti-PLA2R antibodies pretransplant, female sex, younger age, high proteinuria pretransplant, the longest interval from initial disease to end-stage chronic kidney disease, and the combination of alleles HLA DQA1 05:01 and HLA DQB1 02:01. In the pretransplant period, 37 (26.61%) patients had a positive serum test and 18 (12.94%) patients had a positive biopsy stain for anti-PLA2R antibodies. The sensitivity of the pretransplant positive serum test for these antibodies ranges from 57% to 85.30% and the specificity is 85.10-100%. A total of 81.80% of patients who received rituximab as treatment for iMN recurrence achieved complete and partial remission, while 18.20% had no response to treatment. iMN recurrence was not associated with significantly different rates of graft loss (odds ratio = 1.03, 95% CI: 0.52-2.04, p = 0.524, I2 = 0.00%). Recurrence of iMN was not associated with increased risk of graft loss independently of whether patients were treated with rituximab (OR: 0.98, 95% CI: 0.39-2.50, I2: 0%) or not (OR: 1.22, 95% CI: 0.58-2.59, I2: 3.8%). Patients with iMN recurrence who achieved remission had significantly reduced risk of graft loss (OR: 0.14, 95% CI: 0.03 to 0.73). The main outcome from this systematic review is that there is no statistically significant difference in graft survival in patients with iMN recurrence compared to those without recurrence in long-term follow-up. The achievement of remission is associated with significantly reduced risk of graft loss.

This systematic review explores the association between HLA-DQB1 genes and scleroderma, a chronic autoimmune disease characterized by collagen synthesis dysregulation and tissue fibrosis. A thorough investigation was conducted by utilizing Google Scholar and PubMed to search for relevant studies in the English language. Two independent reviewers were involved in the process of screening for appropriate studies. A limitation of the exclusion of non-English studies potentially introduces language bias. Inclusion criteria focused on articles investigating the association between HLA genes and scleroderma, providing data on patient and control groups. Risk of bias was conducted using the NIH Quality Assessment Tool for Case-Control Studies. The analyses focused on odds ratios (OR) as a measure of the strength of the association of HLA genes with disease susceptibility. Subgroup analyses were performed for Caucasian and Asian samples, along with a combined analysis. In Caucasian samples, DQB1*02:02 was associated with lower odds of scleroderma (OR=0.51, 95% CI [0.41, 0.63]), while DQB1*03:01 was associated with higher odds (OR=1.55, 95% CI [1.22, 1.97]). In Asian samples, DQB1*04:02 and DQB1*06:01 were associated with higher odds of scleroderma (OR=1.51, 95% CI [1.01, 2.24] and OR=1.33, 95% CI [1.06, 1.67], respectively), while DQB1*06:04 was associated with lower odds (OR=0.55, 95% CI [0.37, 0.82]). Combined samples showed decreased odds of scleroderma in DQB1*06:03 (OR=0.68, 95% CI [0.48, 0.95]) and DQB1*06:04 (OR=0.56, 95% CI [0.39, 0.81]). Future research should explore the interaction between HLA genes and environmental factors to enhance early detection and intervention strategies for individuals at risk of developing scleroderma.