scholarly journals Retrospective in silico HLA predictions from COVID-19 patients reveal alleles associated with disease prognosis

2020 ◽  
Author(s):  
René L. Warren ◽  
Inanç Birol
Keyword(s):  
In Silico ◽  
Statistical Significance ◽  
Significant Risk ◽  
Human Leukocyte ◽  
Hla Class I ◽  
Negative Control ◽  
Control Group ◽  
Clinical Value ◽  
Disease Prognosis ◽  
Increased Risk

ABSTRACTBackgroundThe Human Leukocyte Antigen (HLA) gene locus plays a fundamental role in human immunity, and it is established that certain HLA alleles are disease determinants.MethodsBy combining the predictive power of multiple in silico HLA predictors, we have previously identified prevalent HLA class I and class II alleles, including DPA1*02:02, in two small cohorts at the COVID-19 pandemic onset. Since then, newer and larger patient cohorts with controls and associated demographic and clinical data have been deposited in public repositories. Here, we report on HLA-I and HLA-II alleles, along with their associated risk significance in one such cohort of 126 patients, including COVID-19 positive (n=100) and negative patients (n=26).ResultsWe recapitulate an enrichment of DPA1*02:02 in the COVID-19 positive cohort (29%) when compared to the COVID-negative control group (Fisher’s exact test [FET] p=0.0174). Having this allele, however, does not appear to put this cohort’s patients at an increased risk of hospitalization. Inspection of COVID-19 disease severity outcomes reveal nominally significant risk associations with A*11:01 (FET p=0.0078), C*04:01 (FET p=0.0087) and DQA1*01:02 (FET p=0.0121).ConclusionsWhile enrichment of these alleles falls below statistical significance after Bonferroni correction, COVID-19 patients with the latter three alleles tend to fare worse overall. This is especially evident for patients with C*04:01, where disease prognosis measured by mechanical ventilation-free days was statistically significant after multiple hypothesis correction (Bonferroni p = 0.0023), and may hold potential clinical value.

scholarly journals HLA alleles measured from COVID-19 patient transcriptomes reveal associations with disease prognosis in a New York cohort

PeerJ ◽  
2021 ◽  
Vol 9 ◽  
pp. e12368
Author(s):  
René L. Warren ◽  
Inanc Birol
Keyword(s):  
Statistical Significance ◽  
Severe Disease ◽  
Significant Risk ◽  
Human Leukocyte ◽  
Negative Control ◽  
Control Group ◽  
Clinical Value ◽  
Hla Alleles ◽  
Disease Prognosis ◽  
Increased Risk

Background The Human Leukocyte Antigen (HLA) gene locus plays a fundamental role in human immunity, and it is established that certain HLA alleles are disease determinants. Previously, we have identified prevalent HLA class I and class II alleles, including DPA1*02:02, in two small patient cohorts at the COVID-19 pandemic onset. Methods We have since analyzed a larger public patient cohort data (n = 126 patients) with controls, associated demographic and clinical data. By combining the predictive power of multiple in silico HLA predictors, we report on HLA-I and HLA-II alleles, along with their associated risk significance. Results We observe HLA-II DPA1*02:02 at a higher frequency in the COVID-19 positive cohort (29%) when compared to the COVID-negative control group (Fisher’s exact test [FET] p = 0.0174). Having this allele, however, does not appear to put this cohort’s patients at an increased risk of hospitalization. Inspection of COVID-19 disease severity outcomes, including admission to intensive care, reveal nominally significant risk associations with A*11:01 (FET p = 0.0078) and C*04:01 (FET p = 0.0087). The association with severe disease outcome is especially evident for patients with C*04:01, where disease prognosis measured by mechanical ventilation-free days was statistically significant after multiple hypothesis correction (Bonferroni p = 0.0323). While prevalence of some of these alleles falls below statistical significance after Bonferroni correction, COVID-19 patients with HLA-I C*04:01 tend to fare worse overall. This HLA allele may hold potential clinical value.

scholarly journals Clinical value of a screening tool for tumor predisposition syndromes in childhood cancer patients (TuPS): a prospective, observational, multi-center study

2021 ◽  
Author(s):  
Floor A. M. Postema ◽  
Saskia M. J. Hopman ◽  
Corianne A. J. M. de Borgie ◽  
Cora M. Aalfs ◽  
Jakob K. Anninga ◽  
...  
Keyword(s):  
Screening Tool ◽  
Clinical Care ◽  
False Negative ◽  
Negative Control ◽  
Control Group ◽  
Clinical Value ◽  
Variant Of Uncertain Significance ◽  
Multi Center Study ◽  
Center Study ◽  
Genetic Consultation

AbstractRecognizing a tumor predisposition syndrome (TPS) in a child with cancer is of clinical relevance. Earlier we developed a screening tool to increase diagnostic accuracy and clinical efficiency of identifying TPSs in children with cancer. Here we report on the value of this tool in clinical practice. TuPS is a prospective, observational, multi-center study including children newly diagnosed with cancer from 2016 to 2019 in the Netherlands. Children in whom a TPS had been diagnosed before the cancer diagnosis were excluded. The screening tool consists of a checklist, 2D and 3D photographic series and digital assessment of these by a clinical geneticist. If a TPS was suspected, the patient was assessed positive and referred for routine genetic consultation. Primary aim was to assess the clinical value of this new screening tool. Of the 363 included patients, 57% (208/363) were assessed positive. In 15% of patients (32/208), the 2D photographic series with (n = 12) or without (n = 20) 3D photographs were decisive in the positive assessment. In 2% (4/208) of positive assessed patients, a TPS was diagnosed, and in an additional 2% (4/208) a germline variant of uncertain significance was found. Thirty-five negatively assessed patients were evaluated through routine genetic consultation as controls, in none a TPS was detected. Using the screening tool, 57% of the patients were assessed as suspected for having a TPS. No false negative results were identified in the negative control group in the clinical care setting. The observed prevalence of TPS was lower than expected, due to selection bias in the cohort.

scholarly journals The Connection of the Level of Estradiol in Serum and Obesity with the Endometrial Bleeding in Postmenopausal Women

2019 ◽  
Vol 7 (1) ◽  
pp. 88-91 ◽  
Author(s):  
Valentina Tofiloska ◽  
Maria Krstevska ◽  
Ana Daneva-Markova ◽  
Viktorija Jovanovska
Keyword(s):  
Endometrial Cancer ◽  
Statistical Significance ◽  
Abnormal Uterine Bleeding ◽  
Control Group ◽  
Prospective Clinical Study ◽  
Study Group ◽  
Gynecology And Obstetrics ◽  
Increased Risk ◽  
Significant Difference ◽  
Post Menopausal

BACKGROUND: Postmenopausis is a period that begins one year after the last menstrual period. Abnormal uterine bleeding could be of different origins. AIM: This study aimed to determine the association of serum estrogen hormone levels and obesity with the occurrence of endometrial bleeding in post-menopausal women. MATERIAL AND METHODS: Prospective clinical study involving 120 postmenopausal patients treated at the University Clinic for Gynecology and Obstetrics-Skopje, divided into two groups: control and study. The control group consisted of 40 postmenopausal patients without endometrial bleeding, hospitalised and operated due to urogenital pathology. The study group consisted of 80 patients with endometrial bleeding who were divided into three subgroups according to the thickness of the endometrium: from 5-8 mm, 8-11 mm and above 11 mm. In all subjects, estradiol and BMI was determined. RESULTS: Estradiol levels were statistically higher in the study group compared to control while statistically significant difference among the three subgroups according to the thickness of the endometrium about the levels of estradiol in blood is not found. About BMI, the results showed that there was no statistical significance between the two examined groups. CONCLUSION: Patients with endometrial bleeding have increased levels of estradiol and are at increased risk of endometrial cancer about controls, the likelihood of endometrial cancer significantly increases by 1,108 times.

scholarly journals Class-I human leukocyte alleles in leprosy patients from Southern Brazil

2011 ◽  
Vol 44 (5) ◽  
pp. 616-620 ◽  
Author(s):  
Danilo Santana Alessio Franceschi ◽  
Luiza Tamie Tsuneto ◽  
Priscila Saamara Mazini ◽  
William Sergio do Sacramento ◽  
Pâmela Guimarães Reis ◽  
...  
Keyword(s):  
Human Leukocyte ◽  
Hla Class I ◽  
Innate Immune ◽  
Class I ◽  
Control Group ◽  
Southern Brazil ◽  
Hla Genotyping ◽  
Leprosy Patients ◽  
Direct Counting

INTRODUCTION: The present study was designed to investigate a possible role of HLA (histocompatibility leucocyte antigen) class-I alleles (HLA-A, -B, and -C) in leprosy patients from Southern Brazil. METHODS: Two hundred and twenty-five patients with leprosy and 450 individuals for the control group were involved in this research. HLA genotyping was performed through PCR-SSO protocols (One Lambda, USA); the frequency of these alleles was calculated in each group by direct counting, and the frequencies were then compared. RESULTS: There was an association between HLA-A*11 (6.9% vs 4.1%, p=0.0345, OR=1.72, 95% CI=1.05-2.81), HLA-B*38 (2.7% vs. 1.1%, p=0.0402, OR=2.44, 95% CI=1.05-5.69), HLA-C*12 (9.4% vs. 5.4%, p=0.01, OR=1.82, 95% CI=1.17-2.82), and HLA-C*16 (3.1% vs. 6.5%, p=0.0124, OR=0.47, 95% CI=0.26-0.85) and leprosy per se. In addition, HLA-B*35, HLA-C*04, and HLA-C*07 frequencies were different between lepromatous (LL) and tuberculoid (TT) patients. However, after adjusting for the number of alleles compared, Pc values became nonsignificant. CONCLUSIONS: Although our results do not support the previous findings that HLA class-I alleles play a role in leprosy pathogenesis, we suggest new studies because of the importance of the association between the HLA and KIR in the innate immune response to leprosy.

scholarly journals Analysis of Chronic Periodontitis in Tonsillectomy Patients: A Longitudinal Follow-Up Study Using a National Health Screening Cohort

2020 ◽  
Vol 10 (10) ◽  
pp. 3663 ◽  
Author(s):  
Soo Hwan Byun ◽  
Chanyang Min ◽  
Yong Bok Kim ◽  
Heejin Kim ◽  
Sung Hun Kang ◽  
...  
Keyword(s):  
Subgroup Analysis ◽  
Chronic Periodontitis ◽  
Index Date ◽  
Statistical Significance ◽  
Significant Risk ◽  
Control Group ◽  
Follow Up Study ◽  
Region Of Residence ◽  
National Cohort

This study aimed to compare the risk of chronic periodontitis (CP) between participants who underwent tonsillectomy and those who did not (control participants) using a national cohort dataset. Patients who underwent tonsillectomy were selected from a total of 514,866 participants. A control group was included if participants had not undergone tonsillectomy from 2002 to 2015. The number of CP treatments was counted from the date of the tonsillectomy treatment. Patients who underwent tonsillectomy were matched 1:4 with control participants who were categorized based on age, sex, income, and region of residence. Finally, 1044 patients who underwent tonsillectomy were matched 1:4 with 4176 control participants. The adjusted estimated value of the number of post-index date (ID) CP did not reach statistical significance in any post-ID year (each of p > 0.05). In another subgroup analysis according to the number of pre- ID CP, it did not show statistical significance. This study revealed that tonsillectomy was not strongly associated with reducing the risk of CP. Even though the tonsils and periodontium are located adjacently, and tonsillectomy and CP may be related to bacterial inflammation, there was no significant risk of CP in patients undergoing tonsillectomy.

scholarly journals Hierarchy of resistance to cervical neoplasia mediated by combinations of killer immunoglobulin-like receptor and human leukocyte antigen loci

2005 ◽  
Vol 201 (7) ◽  
pp. 1069-1075 ◽  
Author(s):  
Mary Carrington ◽  
Sophia Wang ◽  
Maureen P. Martin ◽  
Xiaojiang Gao ◽  
Mark Schiffman ◽  
...  
Keyword(s):  
Cell Activation ◽  
Nk Cell ◽  
Human Leukocyte ◽  
Hla Class I ◽  
Cervical Neoplasia ◽  
Leukocyte Antigen ◽  
Hla Ligand ◽  
Increased Risk ◽  
Ligand Interactions ◽  
Cell Inhibition

Killer immunoglobulin-like receptor (KIR) recognition of specific human histocompatibility leukocyte antigen (HLA) class I allotypes contributes to the array of receptor–ligand interactions that determine natural killer (NK) cell response to its target. Contrasting genetic effects of KIR/HLA combinations have been observed in infectious and autoimmune diseases, where genotypes associated with NK cell activation seem to be protective or to confer susceptibility, respectively. We show here that combinations of KIR and HLA loci also affect the risk of developing cervical neoplasia. Specific inhibitory KIR/HLA ligand pairs decrease the risk of developing neoplasia, whereas the presence of the activating receptor KIR3DS1 results in increased risk of disease, particularly when the protective inhibitory combinations are missing. These data suggest a continuum of resistance conferred by NK cell inhibition to susceptibility involving NK cell activation in the development of cervical neoplasia and underscore the pervasive influence of KIR/HLA genetic variation in human disease pathogenesis.

scholarly journals BIOCHEMICAL AND HAEMATOLOGICAL CHANGES ASSOCIATED WITH TRANSPLACENTAL CONGENITAL MALARIA IN KOGI STATE, NORTH CENTRAL NIGERIA

2021 ◽  
Author(s):  
Shedrack Egbunu Akor ◽  
Dickson Achimugu Musa ◽  
Akogu SPO
Keyword(s):  
Cord Blood ◽  
Statistical Significance ◽  
Negative Control Group ◽  
Negative Control ◽  
Control Group ◽  
Blood Biochemical ◽  
Significant Difference ◽  
Haematological Changes ◽  
Haematological Indices ◽  
Congenital Malaria

Background: Transplacental congenital malaria is a vertical transplacental transmission of malaria parasites from the mother to the baby in utero or perinatally during labor. Cord blood that conveyed oxygen and nutrients from mother to fetus and return with carbon dioxide and other waste materials can transmit malaria pathogen. This study is aim to establish early diagnosis of transplacental congenital malaria using cord blood biochemical and haematological indices. Cord blood from 164 babies delivered at three hospitals in Kogi State between January and December, 2020 were microscopically investigated for malaria parasite. Biochemical and Haematological analyses were done using SYSMEX XP 300, Roche 9180 and VIS Spectrophotometer model 721. The data obtained were expressed as mean plus or minus standard deviation using SPSS 23. The indicator level of statistical significance was set at p<0.05. The results showed significant (p<0.05) decreased in values of WBC, platelet, sodium, potassium, urea, creatinine, RBC, PCV, haemoglobin and MCHC in malaria infected cord blood in comparison to malaria negative control group. Significant (P<0.05) increased activities of liver enzymes (AST, ALT, ALP), total protein, bicarbonate and chloride in malaria infected cord blood when compared with malaria negative group. However, no statistically significant difference in lymphocyte, MCV, MCH, neutrophil and mixed of both malaria infected and malaria negative cord blood. This study suggests that cord blood biochemical and haematological indices can be used to diagnose and manage transplacental congenital malaria in fetus and neonates. Keywords: Transplacental, Biochemical, Haematological and Congenital Malaria.

scholarly journals In silico investigation of binding affinities between human leukocyte antigen class I molecules and SARS-CoV-2 virus spike and ORF1ab proteins

2021 ◽  
Author(s):  
Spyros A. Charonis ◽  
Effie-Photini Tsilibary ◽  
Apostolos P. Georgopoulos
Keyword(s):  
Human Leukocyte Antigen ◽  
In Silico ◽  
Human Leukocyte ◽  
Hla Class I ◽  
Hla Class Ii ◽  
Class I ◽  
Binding Affinities ◽  
S Protein ◽  
Leukocyte Antigen ◽  
Hla Class I Molecules

Aim: The novel coronavirus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes coronavirus disease 2019, a global pandemic. There is hence an urgent need for effective approaches to understand the mechanism of viral interaction with immune cells that lead to viral elimination and subsequent long-term immunity. The first, immediate response to the viral infection involves mobilization of native immunity and human leukocyte antigen (HLA) class I mechanisms to kill infected cells and eliminate the virus. The second line of defense involves the activation of HLA class II system for the production of antibodies against the virus which will add to the elimination of the virus and prevent future infections. In a previous study, investigated the relations between SARS-CoV-2 spike glycoprotein (S protein) and HLA class II alleles were investigaed; here report on the relations of the S protein and the open reading frame 1ab (ORF1ab) of SARS-CoV-2 to HLA class I alleles. Methods: An in silico sliding window approach was used to determine exhaustively the binding affinities of linear epitopes of 10 amino acid length (10-mers) to each of 61 common (global frequency ≥ 0.01) HLA class I molecules (17, 24 and 20 from gene loci A, B and C, respectively). A total of 8,354 epitopes were analyzed; 1,263 from the S protein and 7,091 from ORF1ab. Results: HLA-A genes were the most effective at binding SARS-CoV-2 epitopes for both spike and ORF1ab proteins. Good binding affinities were found for all three genes and were distributed throughout the length of the S protein and ORF1ab polyprotein sequence. Conclusions: Common HLA class I molecules, as a population, are very well suited to binding with high affinity to SARS-CoV-2 spike and ORF1ab proteins and hence should be effective in aiding the early elimination of the virus.

scholarly journals Socioeconomic Burden of Rising Methamphetamine-Associated Heart Failure Hospitalizations in California From 2008 to 2018

2021 ◽  
Author(s):  
Susan X. Zhao ◽  
Andres Deluna ◽  
Kate Kelsey ◽  
Clifford Wang ◽  
Aravind Swaminathan ◽  
...  
Keyword(s):  
Heart Failure ◽  
Health Planning ◽  
Statistical Significance ◽  
Negative Control Group ◽  
International Classification Of Diseases ◽  
Negative Control ◽  
Control Group ◽  
Public Health Response ◽  
Classification Of Diseases ◽  
Age Adjusted Rates

BACKGROUND: Methamphetamine-associated cardiomyopathy/heart failure (MethHF) is an increasingly recognized disease entity in the context of a rising methamphetamine (meth) epidemic that most severely impacts the western United States. Using heart failure (HF) hospitalization data from the Office of Statewide Health Planning and Development, this study aimed to assess trend and disease burden of MethHF in California. METHODS: Adult patients (≥18 years old) with HF as primary hospitalization diagnosis between 2008 and 2018 were included in this study. The association with Meth (MethHF) and those without (non-MethHF) were determined by meth-related International Classification of Diseases -based secondary diagnoses. Statistical significance of trends in age-adjusted rates of hospitalization per 100 000 adults were evaluated using nonparametric analysis. RESULTS: Between 2008 and 2018, 1 033 076 HF hospitalizations were identified: 42 565 were MethHF (4.12%) and 990 511 (95.88%) were non-MethHF. Age-adjusted MethHF hospitalizations per 100 000 increased by 585% from 4.1 in 2008 to 28.1 in 2018, while non-MethHF hospitalizations decreased by 6.0% from 342.3 in 2008 to 321.6 in 2018. The rate of MethHF hospitalization increase more than doubled that of a negative control group with urinary tract infection and meth-related secondary diagnoses (7.82-fold versus 3.48-fold, P <0.001). Annual inflation–adjusted hospitalization charges because of MethHF increased by 840% from $41.5 million in 2008 to $390.2 million in 2018, as compared with an 82% increase for all HF hospitalization from $3.503 billion to $6.376 billion. Patients with MethHF were significantly younger (49.64±10.06 versus 72.20±14.97 years old, P <0.001), predominantly male (79.1% versus 52.4%, P <0.001), with lower Charlson Comorbidity Index, yet they had longer length of stay, more hospitalizations per patient, and more procedures performed during their stays. CONCLUSIONS: MethHF hospitalizations increased sharply during the study period and contributed significantly to the HF hospitalization burden in California. This emerging HF phenotype, which engenders considerable financial and societal costs, calls for an urgent and concerted public health response to contain its spread.

scholarly journals Carotid Arterial Stiffness and Cardiometabolic Profiles in Women with Fibromyalgia

Biomedicines ◽  
2021 ◽  
Vol 9 (12) ◽  
pp. 1786
Author(s):  
Yunkyung Kim ◽  
Geun-Tae Kim ◽  
Jihun Kang
Keyword(s):  
Risk Factors ◽  
Arterial Stiffness ◽  
Central Obesity ◽  
Cardiometabolic Risk ◽  
Statistical Significance ◽  
Cardiometabolic Risk Factors ◽  
Control Group ◽  
Increased Risk ◽  
Carotid Arterial ◽  
High Triglyceride

Background: The present study aimed to evaluate the association between FM and cardiometabolic risk factors and carotid arterial stiffness in FM patients. Methods: The cardiometabolic risk profile was defined based on the Adult Treatment Panel III panel. Carotid intimal media thickness (cIMT) and arterial stiffness were assessed using high-resolution ultrasonography. Multivariate logistic analysis was performed to estimate the association between FM and cardiometabolic risk factors. We used a general linear regression to compare the cIMT and carotid beta-index between the participants with and without FM. Pearson’s coefficient was calculated to evaluate the potential correlation between cardiometabolic risk profiles, cIMT, and arterial stiffening in FM. Results: FM participants showed a higher risk of central obesity (odds ratio [OR] = 3.21, 95% confidence interval [CI] 1.49, 6.91), high triglyceride (OR = 4.73, 95% CI 2.29, 9.79), and impaired fasting glucose (IFG) (OR = 4.27, 95% CI 2.07, 8.81) compared to the control group. The FM group exhibited higher beta-index values than the control group (p = 0.003). Although IFG and triglyceride glucose index showed a tendency to correlate with the beta-index, statistical significance was not observed. Conclusions: FM was associated with an increased risk of central obesity, high triglyceride levels, and IFG. Furthermore, advanced arterial stiffness of the carotid artery was observed in FM, which might be correlated with insulin resistance.

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