Project description:HLA class I alleles constitute established risk factors for non-infectious uveitis and preemptive genotyping of HLA class I alleles is standard practice in the diagnostic work-up. The HLA-A29 serotype is indispensable to Birdshot Uveitis (BU) and renders this enigmatic eye condition a unique model to better understand how the antigen processing and presentation machinery contributes to non-infectious uveitis or chronic inflammatory conditions in general. This review will discuss salient points regarding the protein structure of HLA-A29 and how key amino acid positions impact the peptide binding preference and interaction with T cells. We discuss to what extent the risk genes ERAP1 and ERAP2 uniquely affect HLA-A29 and how the discovery of a HLA-A29-specific submotif may impact autoantigen discovery. We further provide a compelling argument to solve the long-standing question why BU only affects HLA-A29-positive individuals from Western-European ancestry by exploiting data from the 1000 Genomes Project. We combine novel insights from structural and immunopeptidomic studies and discuss the functional implications of genetic associations across the HLA class I antigen presentation pathway to refine the etiological basis of Birdshot Uveitis.
Project description:BackgroundA recent study showed that the ABO gene, chr 9q34.2, which determines blood type, may affect COVID-19 disease severity, although this result has not been reproducible. A UK study of 2200 COVID-19 patients found no relationship of ABO blood type to disease severity. A Danish study identified ABO blood group as a risk factor for SARS-CoV-2 infection but not for hospitalization or death from COVID-19.AimIn the current study, we wished to analyze the relationship of ABO blood group and the ABO genetic locus to COVID-19 test positivity and mortality in subjects from the UK Biobank (UKB).MethodsABO blood type is from UKB data field 23165. Blood type was imputed for genotyped UK Biobank participants using three SNPs (rs505922, rs8176719, and rs8176746) in the ABO gene on chromosome 9q34.2. We analyzed the chromosome 9 snp rs657152 to assess the relationship of the ABO locus to COVID-19 test positivity and mortality.ResultsCOVID-19 test results (negative or positive) were not related to blood group in males (p = 0.977, two tailed Fisher exact test) or females (p = 0.548). COVID-19 outcomes (alive or died) were not related to blood group in males (p = 0.102, two tailed Fisher exact test) or females (p = 0.226). We found no significant relationship of rs657152 to COVID-19 test positivity or mortality.ConclusionWe were not able to confirm that ABO blood group influences risk of COVID-19 infection or outcome.
Project description:Pediatric hematopoietic stem cell transplant (HSCT) is an intensive treatment that can be life-threatening. All family members experience distress. We conducted a grounded theory study using a family systems-expressive arts framework to develop a theoretical understanding of the family experience of HSCT. Six families (15 family members) participated in two interviews, drew an image, and were guided through a "dialoguing with images" process. Participants did not always perceive HSCT as an experience they had lived as a family and were surprised to hear other family members' experiences. While one mother drew, she suddenly understood it was not only her ill child, but the entire family who had "fallen down the rabbit hole." The family experience of HSCT is described across (a) the pre-HSCT trajectory, (b) family fragmentation (hospitalization), and (c) family reintegration. We identified a critical need for targeted family intervention during the transition into HSCT, throughout and following hospitalization.
Project description:BackgroundBlood group type A has been associated with increased susceptibility for coronavirus disease 2019 (COVID-19) infection when compared to group O. The aim of our study was to examine outcomes in hospitalized COVID-19 patients among blood groups A and O.MethodsThis is an observational study. Kruskal-Wallis and Chi-square tests were used to compare continuous and categorical variables. Multivariable logistic regression models were used to examine association of blood groups with rates of mortality and severity of disease. All adult patients (> 18 years) admitted with COVID-19 infection between March 1, 2020 and March 10, 2021 at a large community hospital in Northeast Georgia were included. We compared mortality, severity of disease (use of mechanical ventilation, vasopressor, and acute renal failure), rates of venous thromboembolism and inflammatory markers between the blood groups. We used multivariable logistic regression model to adjust for demographical and clinical characteristics, use of COVID-19 medications and severity.ResultsA total of 3,563 of 5,204 admitted patients had information on blood groups. Of these, 1,301 (36.5%) were group A, 377 (10.6 %) were group B, 133 (3.7%) were group AB and 1,752 (49.2%) were group O. On adjusted analysis, there were no significant differences in rates of intensive care unit (ICU) admissions, mechanical ventilation, vasopressors, acute renal failure, venous thromboembolism and readmission rate between the blood groups A and O. In-hospital mortality was also not statistically different among the blood groups A and O (17.5% vs. 20.1%; P = 0.07). On adjusted analysis, in-hospital mortality was not lower in blood groups O (odds ratio (OR): 1.06; 95% confidence interval (CI): 0.80 - 1.40, P = 0.70).ConclusionsOnce hospitalized with COVID-19 infection, blood groups A and O are not associated with increased severity or in-hospital mortality.
Project description:BackgroundSusceptibility to Covid-19 has been found to be associated with the ABO blood group, with O type individuals being at a lower risk. However, the underlying mechanism has not been elucidated. Here, we aimed to test the hypothesis that Covid-19 patients might have lower levels of ABO antibodies than non-infected individuals as they could offer some degree of protection.MethodsAfter showing that the viral spike protein harbors the ABO glycan epitopes when produced by cells expressing the relevant glycosyltransferases, like upper respiratory tract epithelial cells, we enrolled 290 patients with Covid-19 and 276 asymptomatic controls to compare their levels of natural ABO blood group antibodies.ResultsWe found significantly lower IgM anti-A + anti-B agglutination scores in blood group O patients (76.93 vs 88.29, P-value = 0.034) and lower levels of anti-B (24.93 vs 30.40, P-value = 0.028) and anti-A antibodies (28.56 vs 36.50, P-value = 0.048) in blood group A and blood group B patients, respectively, compared to controls.ConclusionIn this study, we showed that ABO antibody levels are significantly lower in Covid-19 patients compared to controls. These findings could indicate that patients with low levels of ABO antibodies are at higher risk of being infected.
Project description:The identification of factors associated to COVID-19 mortality is important to design effective containment measures and safeguard at-risk categories. In the last year, several investigations have tried to ascertain key features to predict the COVID-19 mortality tolls in relation to country-specific dynamics and population structure. Most studies focused on the first wave of the COVID-19 pandemic observed in the first half of 2020. Numerous studies have reported significant associations between COVID-19 mortality and relevant variables, for instance obesity, healthcare system indicators such as hospital beds density, and bacillus Calmette-Guerin immunization. In this work, we investigated the role of ABO/Rh blood groups at three different stages of the pandemic while accounting for demographic, economic, and health system related confounding factors. Using a machine learning approach, we found that the "B+" blood group frequency is an important factor at all stages of the pandemic, confirming previous findings that blood groups are linked to COVID-19 severity and fatal outcome.
Project description:To analyse gene expression pattern in different disease state of COVID-19 patients. Experimental workflow: 1) rRNA was removed by using RNase H method, 2) QAIseq FastSelect RNA Removal Kit was used to remove the Globin RNA, 3) The purified fragmented cDNA was combined with End Repair Mix, then add A-Tailing Mix, mix well by pipetting, incubation, 4) PCR amplification, 5) Library quality control and pooling cyclization, 6) The RNA library was sequenced by MGI2000 PE100 platform with 100bp paired-end reads. Analysis steps: 1) RNA-seq raw sequencing reads were filtered by SOAPnuke (Li et al., 2008) to remove reads with sequencing adapter, with low-quality base ratio (base quality < 5) > 20%, and with unknown base (’N’ base) ratio > 5%. 2) Reads aligned to rRNA by Bowtie2 (v2.2.5) (Langmead and Salzberg, 2012) were removed. 3) The clean reads were mapped to the reference genome using HISAT2 (Kim et al., 2015). Bowtie2 (v2.2.5) was applied to align the clean reads to the transcriptome. 4)Then the gene expression level (FPKM) was determined by RSEM (Li and Dewey, 2011). Genes with FPKM > 0.1 in at least one sample were retained.