ABSTRACT
HLA molecules play a key role in transplant medicine and disease pathogenesis, being a useful tool in predicting disease progression and identifying potential solid organ donors (SOD). The Coronavirus disease 2019 (SARS-CoV-2) pandemic had a huge worldwide impact, which strongly affected the activity of different transplant programs. So far, it has been shown that HLA type may be a crucial differentiator between individuals who have varying occurrence, morbidity, and mortality response to SARS-CoV-2. In this work, we investigated if differences in the frequency of SOD HLA alleles, were impacted during SARS-CoV-2 pandemic. We performed a retrospective file audit of all HLA-typings done in 2 subsets of SOD pre-pandemic period (ppp) (n = 379) and pandemic period (pp) (n = 351), collected in equivalent timeframes. We discuss data for the major HLA-A, HLA-B, HLA-C, and HLA-DRB1 allele groups at serological phenotyping level. Overall, there was a 7% SOD decrease in the pp. Considering both periods, the most common allele groups were HLA-A2, HLA-B35, HLA-Cw7, HLA-DR7 and HLA-DQ2. For the ppp group, the most common alleles were HLA-A2, HLA-B35, HLA-Cw7, HLADR13 and HLA-DQ2, while in the pp group the most common alleles were HLA-A2, HLA-B44, HLA-Cw7, HLA-DR4 and HLA-DQ2. When comparing both populations at the serological phenotyping level an increased in relative frequency was found for 10, 12, 8, 8 and 2, and a decreased was found for 10, 24, 8, 6 and 5 for HLA-A, -B, -C, -DR and -DQ, respectively. The significant variation within the HLA frequencies between the different pre-pandemic and pandemic groups highlights the value of population-specific HLA-typing. Furthermore, the identification of different frequencies among both populations will impact in patients HLA compatibility with SOD thus impacting their transplantability.
ABSTRACT
BACKGROUND: Turmeric (curcumin) is a commonly used over-the-counter herbal product whose uses include diarrhea, arthritis, cancer and even COVID-19. Recently turmeric has been implicated in cases of clinically apparent liver injury with jaundice. The aim of this case series is to describe the clinical, histologic and human leukocyte antigen (HLA) associations of turmeric-associated hepatotoxicity as seen in the U.S. Drug Induced Liver Injury Network (DILIN) Prospective Study. METHODS: All adjudicated cases enrolled in DILIN between 2003-2020 with turmeric as an implicated product were reviewed. Causality was assessed using a 5-point expert opinion score. Available products were collected and analyzed for the presence of turmeric using ultra-high-performance liquid chromatography. Genetic analyses included HLA sequencing. RESULTS: Of 1697 cases of drug-induced liver injury judged to be definite, highly likely or probable (high confidence), nine (0.5%) were attributed to turmeric, all of which were enrolled since 2012, and 6 since 2017 (Figure). The 9 cases included 7 women, 8 whites, with a mean age of 51 years (range, 35-62 years) and BMI 25 kg/m2 (range, 15-40). Seven patients used alcohol, but none to excess, and none had underlying liver disease. Turmeric was used for an average of 102 days before onset of injury (range, 30-425 days). Initial mean ALT was 1179 U/L (range, 328-2245), ALP 211 U/L (41-441), total bilirubin 5.9 mg/dL (1.2-10.8), and INR 1.0 (0.9-1.2). Six patients developed jaundice, and serum bilirubin peaked at 9.6 mg/dL (0.8-26), and INR 2.3 (1.0- 9.7). Liver injury was hepatocellular in 8 patients (mean R = 22). Five patients had elevated antinuclear antibody (ANA) titer and two anti-smooth muscle (ASM) antibody, but none were treated with corticosteroids. Liver biopsy in 5 patients showed portal and lobular mixed inflammatory infiltrates with lymphocytes and eosinophils typical of drug-induced liver injury. Five patients were hospitalized, and one patient died of acute liver failure. Chemical analysis confirmed the presence of turmeric in all 7 products analyzed;3 also contained piperine (black pepper), and none contained green tea. Of 7 patients with HLA typing available, 4 carried HLA-B*35:01, a class I HLA allele previously implicated in both green tea and Polygonum multiflorum hepatotoxicity. CONCLUSION: Liver injury due to turmeric appears to be increasing, perhaps, reflecting usage patterns or increased combination with black pepper, which increases its absorption. Turmeric liver injury, similar to that caused by other polyphenolic herbal products, is typically hepatocellular, with a latency of 1 to 6 months, and is linked to HLA-B*35:01. While most cases are self-limited, the injury can be severe and result in death or liver transplantation.
ABSTRACT
introduction. hla alleles play a fundamental role in the development of the immune response against viral infections. objective. Gather the information available on the association of different hla alleles with increased protection or susceptibility;furthermore, the impact on complications associated with sars-cov-2 infection. methodology. An information search was carried out in the Scopus, PubMed/Medline, lilacs and Academic Google databases that answered the research question: What is the association between hla and sars-cov-2 infection and the severity of the illness? Records of clinical trials from the databases of the who International Clinical Trials Platform were included. results. It was found that the hla-a* 25: 01, hla-b* 46: 01 and hla-c* 01: 02 alleles were associated with greater susceptibility to infection, while the hla-a* 02: 01 alleles, hla-a* 24: 02 and hla-b*27: 07 were associated with greater severity of the disease and the alleles hla-a* 02: 02, hla-b* 15: 03 and hla-c* 12: 03 as protective factor in covid-19. conclusions. The association between susceptibility, protection and severity with the different types of hla are mainly reported in silico analysis, and its precision is limited, requiring support based on in vitro and in vivo experimental studies and clinical trials in different populations. A greater focus is needed on the affinity of the various hla alleles by the sars-cov-2 proteome to elucidate the immunopathogenesis of the disease.
ABSTRACT
Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is the etiology of an outbreak Covid-19. SARS-CoV-2 has a structural part consisting of spike glycoprotein, nucleoprotein N, membrane M and envelopes small membrane pentamer E. Immunoinformatic approach epitope analysis is developed to identify both weak and robust epitopes. Our study aims to identify several epitopes present in the spike glycoprotein, envelope, and membrane protein from the SARCoV-2 surface, with the help of insilico approach that highly potential as vaccine candidates. Analysis of antigeninicity was performed with the Kolaskar and Tongaonkar Antigenicity software. Epitope Mapping was analyzed using Linear Epitope Prediction Bepired. The structure of proteins with epitope regions was visualized by software Pyrex and PyMOL. Conserve analysis was performed using bio edit software. HLA mimicry was analyzed through HLAPred software. Molecular docking between the epitope with HLA I and HLA II was validated by Chimera and PyMOL software. The toxicity test for candidate vaccine peptides was carried out using ToxinPred software. Our study found seven potential epitope candidates as vaccine candidates. The seven epitopes were derived from spike proteins (5 epitopes), envelope proteins (1 epitope), and membrane proteins (1 epitope). All epitope codes are conserved and are not the same as HLA in Humans. The docking test results show a value with low affinity so that a strong bond can provide a high immune response. Toxicity tests show that all epitopes are non-toxic and safe to use as vaccine ingredients. Seven peptides from the spike, envelope, membrane protein that showed potential as vaccine candidates against Covid-19.
ABSTRACT
Background: The polymorphic Human Leukocyte Antigens (HLA) play an important role in determining the best matched donor in a haematopoietic stem cell transplant (HSCT). Hence, accurate HLA typing results are crucial to determine the successfulness of a transplant. Most of the patients of hematologic diseases will receive blood transfusion regularly. There is a potential discrepancy result or ambiguous results when a patient already received non-leukoreduced blood component prior to blood sampling for HLA typing. Aims: To determine differences between the HLA typing result from the DNA extracted from blood sample and buccal swab sample. Methods: Blood sample and buccal swab sample were collected from a total of 66 patients with different hematologic diseases and plan to go for haematopoietic stem cell transplant. These patients received at least one pack of red blood cell or platelet between 1 and 14 days prior to blood sample taken. DNA was extracted from all 66 blood samples and 66 buccal swab samples. All samples were typed for six loci (HLA-A, HLA-B, HLA-C, HLA-DRB1, HLA-DQB1 and HLA-DPB1) with Next Generation Sequencing (NGS). NGS was performed in all those samples using the NGSgo-MX6-1 kit. After the library preparation by using NGSgo-LibrX ligation reagents and the NGSgoIndX adapter, it was sequenced in iSeq 100. The results were then analysed with NGSengine software. The results for blood sample and buccal swab sample were then compared. Results: Out of 66 patients, 25 patients received either red blood cell or platelet component prior to blood sample taken for HLA typing. One patient received red blood cell and plasma and the others received red blood cell and platelets before the sample was taken. There are no differences between the HLA typing result from the DNA extracted from blood sample or buccal swab sample for all the 66 patients. The sequencing noise level for both DNA extracted from blood and buccal swab was well separated from the alleles as we can see from the base variation plot. Summary/Conclusions: This preliminary study only focus on the adult patients with hematologic diseases (ALL, AML, CML, MDS, multiple myeloma, DLBCL, hemophagocytic lymphohistiocytosis, NKT Cell lymphoma and severe aplastic anaemia) for the past 1 year. From the findings of this study, blood samples from the patient who underwent blood transfusion can be used for HLA typing instead of using buccal swab samples. This will lower the risk of Covid-19 infection among the healthcare worker who performs the buccal swab sampling from the patient with unknown status of Covid-19 infectivity. However, an extensive study with the appropriate number of samples needed to confirm this finding in the near future.
ABSTRACT
The SARS-CoV-2 coronavirus infection has become a global health concern, causing the COVID-19 pandemic. The disease symptoms and outcomes depend on host immunity, in which the HLA molecules play a distinct role. The present study aimed to detect associations between HLA alleles and COVID-19 susceptibility and severity in Armenians. The study included 299 SARSCoV- 2 infected patients (75 asymptomatic, 102 mild, 122 severe). To compare the allelic frequency profiles of patient groups with those specific to the general population, we used HLA data of 2781 registered donors at the Armenian BMDR. This group was used as a control cohort for age-genotype and allele frequency analyses. Based on the conjoint approach of HLA classical loci genotype and allelic distribution analyses between Armenian population controls and COVID-19 cases we discovered an age-related protective effect of the HLAB∗ 51:01 carriage against COVID-19 severity. In contrast HLA-C∗04:01 allelic-load contributes to the risk for the severe COVID-19 independently from age and classical HLA variables. The HLA-C∗04:01 association with COVID-19 manifestation is rather in concert with female gender and older age. Along with the expected significant decrease in cumulative heterozygosity of HLA class I loci, we report a previously undescribed decrease in heterozygosity of HLA-B locus blueprinted by the HLA-C∗04:01 homozygous genotype. In patients with mild to severe COVID-19, due to high prevalence of HLA-C∗04:01, these effects provide a decrease of the HLA class I loci heterozygosity and a down-modulation of the predicted HLA class I ability to recognize SARS-CoV-2 peptides. The genomic number of HLA-C∗04:01 allele and demographic variables compose the model, in which >15% potential share in the detection of cases with adverse clinical phenotypes belongs to HLA-C∗04:01. The results of study suggest a putative role of HLA-C genetic variation in the development of a specific immune response to COVID-19.