scholarly journals Δccr5 Genotype Is Associated with Mild Form of Nephropathia Epidemica

Viruses ◽  
2019 ◽  
Vol 11 (7) ◽  
pp. 675 ◽  
Author(s):  
Konstantin Kletenkov ◽  
Ekaterina Martynova ◽  
Yuriy Davidyuk ◽  
Emmanuel Kabwe ◽  
Anton Shamsutdinov ◽  
...  
Keyword(s):  
Genetic Markers ◽  
Severe Disease ◽  
Serum Levels ◽  
Nephropathia Epidemica ◽  
Matrix Metalloproteases ◽  
Hantavirus Infection ◽  
Genotype Distribution ◽  
Mild Form ◽  
Ccr5 Gene ◽  
Base Pair Deletion

Nephropathia Epidemica (NE), a mild form of hemorrhagic fever with renal syndrome (HFRS) and linked to hantavirus infection, is endemic in the Republic of Tatarstan. Several genetic markers of HFRS severity have been identified previously, including human leukocyte antigen (HLA) complexes and nucleotide polymorphism in the tumor necrosis factor alpha (TNFα) gene. Still, our understanding of the genetic markers of NE severity remains incomplete. The frequency of the C–C chemokine receptor type 5 (CCR5) gene wild type and gene with 32-base-pair deletion (Δ32CCR5) genotypes in 98 NE samples and 592 controls was analyzed using PCR. Along with the serum levels of 94 analytes, a lack of differences in the CCR5 genotype distribution between NE cases and the general population suggests that the CCR5 genotype does not affect susceptibility to hantavirus infection. However, in NE cases, significant variation in the serum levels of the host matrix metalloproteases between functional CCR5 homozygous and Δ32CCR5 heterozygous patients was detected. Also, the oliguric phase was longer, while thrombocyte counts were lower in functional CCR5 homozygous as compared to heterozygous NE cases. Our data, for the first time, presents the potential role of the CCR5 receptor genotype in NE pathogenesis. Our data suggests that NE pathogenesis in functional CCR5 homozygous and heterozygous NE patients differs, where homozygous cases may have more disintegration of the extracellular matrix and potentially more severe disease.

The −670G>A polymorphism in the FAS gene promoter region influences the susceptibility to systemic sclerosis

2008 ◽  
Vol 68 (4) ◽  
pp. 584-590 ◽  
Author(s):  
V Liakouli ◽  
M Manetti ◽  
A Pacini ◽  
B Tolusso ◽  
C Fatini ◽  
...  
Keyword(s):  
Systemic Sclerosis ◽  
Topoisomerase I ◽  
Gene Promoter ◽  
Serum Levels ◽  
Scleroderma Renal Crisis ◽  
Genotype Distribution ◽  
Healthy Individuals ◽  
Soluble Fas ◽  
Significant Difference ◽  
Pulmonary Arterial

Objective:To evaluate the role of the single-nucleotide polymorphism (SNP) at position −670 in the FAS gene promoter (FAS−670G>A) in influencing the susceptibility, clinical features and severity of systemic sclerosis (SSc).Methods:350 white Italian SSc patients (259 with limited cutaneous SSc (lcSSc) and 91 with diffuse cutaneous SSc (dcSSc)) and 232 healthy individuals were studied. Patients were assessed for the presence of autoantibodies (anticentromere, anti-topoisomerase I (anti-Scl-70) antibodies), interstitial lung disease (ILD), pulmonary arterial hypertension and scleroderma renal crisis. FAS−670G>A SNP was genotyped by PCR restriction fragment length polymorphism assay. Serum levels of soluble FAS (sFAS) were analysed by ELISA.Results:A significant difference in FAS−670 genotype distribution was observed between SSc patients and healthy individuals (p = 0.001). The frequency of the FAS−670A allele was significantly greater in SSc than in controls (p = 0.001). No significant difference in genotype distribution and allele frequencies was observed between lcSSc and dcSSc, although a greater frequency of the FAS−670A allele was found in dcSSc. The FAS−670AA genotype significantly influenced the predisposition to SSc (OR 1.97, 95% CI 1.35 to 2.88, p = 0.001) and to both lcSSc (OR 1.84, 95% CI 1.23 to 2.75, p = 0.003) and dcSSc (OR 2.37, 95% CI 1.41 to 3.99, p = 0.001). FAS−670A allele frequency was greater, although not significantly, in anti-Scl-70 antibody-positive dcSSc and ILD dcSSc. sFAS was significantly higher in patients and controls carrying the FAS−670AA genotype compared with those carrying the FAS−670GG genotype (p = 0.003 in SSc, p = 0.004 in controls).Conclusion:The FAS−670A allele is significantly associated with susceptibility to SSc, suggesting a role for a genetic control of apoptosis in the pathogenesis of the disease.

scholarly journals Impaired immune response mediated by prostaglandin E2 promotes severe COVID-19 disease

PLoS ONE ◽  
2021 ◽  
Vol 16 (8) ◽  
pp. e0255335
Author(s):  
Melanie Ricke-Hoch ◽  
Elisabeth Stelling ◽  
Lisa Lasswitz ◽  
Antonia P. Gunesch ◽  
Martina Kasten ◽  
...  
Keyword(s):  
Prostaglandin E2 ◽  
B Cell ◽  
Life Style ◽  
Severe Disease ◽  
Serum Levels ◽  
Regular Exercise ◽  
Sedentary Life ◽  
Male Sex ◽  
Cox 2 ◽  
Sedentary Life Style

The SARS-CoV-2 coronavirus has led to a pandemic with millions of people affected. The present study finds that risk-factors for severe COVID-19 disease courses, i.e. male sex, older age and sedentary life style are associated with higher prostaglandin E2 (PGE2) serum levels in blood samples from unaffected subjects. In COVID-19 patients, PGE2 blood levels are markedly elevated and correlate positively with disease severity. SARS-CoV-2 induces PGE2 generation and secretion in infected lung epithelial cells by upregulating cyclo-oxygenase (COX)-2 and reducing the PG-degrading enzyme 15-hydroxyprostaglandin-dehydrogenase. Also living human precision cut lung slices (PCLS) infected with SARS-CoV-2 display upregulated COX-2. Regular exercise in aged individuals lowers PGE2 serum levels, which leads to increased Paired-Box-Protein-Pax-5 (PAX5) expression, a master regulator of B-cell survival, proliferation and differentiation also towards long lived memory B-cells, in human pre-B-cell lines. Moreover, PGE2 levels in serum of COVID-19 patients lowers the expression of PAX5 in human pre-B-cell lines. The PGE2 inhibitor Taxifolin reduces SARS-CoV-2-induced PGE2 production. In conclusion, SARS-CoV-2, male sex, old age, and sedentary life style increase PGE2 levels, which may reduce the early anti-viral defense as well as the development of immunity promoting severe disease courses and multiple infections. Regular exercise and Taxifolin treatment may reduce these risks and prevent severe disease courses.

scholarly journals Serum levels of inflammatory cytokines in Rift Valley fever patients are indicative of severe disease

2015 ◽  
Vol 12 (1) ◽  
Author(s):  
Petrus Jansen van Vuren ◽  
Sharon Shalekoff ◽  
Antoinette A. Grobbelaar ◽  
Brett N. Archer ◽  
Juno Thomas ◽  
...  
Keyword(s):  
Inflammatory Cytokines ◽  
Rift Valley ◽  
Rift Valley Fever ◽  
Severe Disease ◽  
Serum Levels ◽  
Valley Fever

scholarly journals P101 Biomarkers of elastin degradation are associated with clinical and biochemically active disease in Crohn’s disease

2020 ◽  
Vol 14 (Supplement_1) ◽  
pp. S185-S186
Author(s):  
M Pehrsson ◽  
V Domislović ◽  
M A Karsdal ◽  
M Brinar ◽  
A Barisic ◽  
...  
Keyword(s):  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Disease Activity ◽  
Activity Index ◽  
Severe Disease ◽  
Matrix Metalloproteases ◽  
Assessment Tools ◽  
Cathepsin G ◽  
Elastin Degradation ◽  
Active Disease

Abstract Background In Crohn’s disease (CD), the extensive and potentially transmural inflammation results in increased activity of both matrix metalloproteases (MMPs) and serine proteases, causing a higher degree of intestinal tissue remodelling. This increased proteolytic activity could potentially cause degradation and loss of function of mechanical and functional matrix proteins, such as elastin. Therefore, we sought to investigate the association between biomarkers of elastin degradation and the disease activity in CD patients. Methods Seventy-two CD patients and 29 healthy donors (HD) were included in the study. Disease activity was determined according to the Crohn’s disease activity index score (CDAI >150) and/or a faecal calprotectin (fCALP >250). Additionally, CD patients were endoscopically assessed according to the simple endoscopic score (SES) for CD. Different protease derived biomarkers of elastin degradation: protease-3 (ELP-3), MMP-7 (ELM-7) and cathepsin-G (EL-CG) was measured in serum by ELISA. One-way ANOVA (Kruskal–Wallis) was applied for the statistical analysis. Results The levels of ELP-3 was significantly elevated in active CD when compared with the HD (p < 0.001), and inactive CD (p < 0.01). Levels of EL-G were significantly elevated when comparing active CD and HD (p < 0.05), with the same result observed for the levels of EL-CG when comparing active CD and the HD (p < 0.05). Endoscopically, ELP-3 was shown significantly elevated in moderate–to-severe CD patients when compared with the HD (p < 0.01). Conclusion In this study, measurements of the elastin degradation markers were capable of differentiating between CD patients with either a clinically active or biochemically active disease, with the biomarker levels being significantly highest in the patients with an active disease. This was also the case when assessing endoscopic disease activity, where the protease-3-derived biomarker levels were highest in patients of moderate-to-severe disease activity. As such, the data provide indications of the beneficial use of these serum biomarkers as additional disease activity assessment tools for CD patients.

Immunoinflammatory Biomarkers in Serum Are Associated with Disease Severity in Atopic Dermatitis

Dermatology ◽  
2021 ◽  
pp. 1-8
Author(s):  
Jesper Grønlund Holm ◽  
Guillem Hurault ◽  
Tove Agner ◽  
Maja Lisa Clausen ◽  
Sanja Kezic ◽  
...  
Keyword(s):  
Atopic Dermatitis ◽  
Disease Severity ◽  
Predictive Models ◽  
Severe Disease ◽  
Serum Levels ◽  
Disease Characteristics ◽  
Immunological Markers ◽  
Chemokine Ligand ◽  
Serum Total Ige ◽  
The Relationship

Background: A growing body of evidence links various biomarkers to atopic dermatitis (AD). Still, little is known about the association of specific biomarkers to disease characteristics and severity in AD. Objective: To explore the relationship between various immunological markers in the serum and disease severity in a hospital cohort of AD patients. Methods: Outpatients with AD referred to the Department of Dermatology, Bispebjerg Hospital, Copenhagen, Denmark, were divided into groups based on disease severity (SCORAD). Serum levels of a preselected panel of immunoinflammatory biomarkers were tested for association with disease characteristics. Two machine learning models were developed to predict SCORAD from the measured biomarkers. Results: A total of 160 patients with AD were included; 53 (33.1%) with mild, 73 (45.6%) with moderate, and 34 (21.3%) with severe disease. Mean age was 29.2 years (range 6–70 years) and 84 (52.5%) were females. Numerous biomarkers showed a statistically significant correlation with SCORAD, with the strongest correlations seen for CCL17/thymus and activation-regulated chemokine (chemokine ligand-17/TARC) and CCL27/cutaneous T cell-attracting-chemokine (CTACK; Spearman R of 0.50 and 0.43, respectively, p < 0.001). Extrinsic AD patients were more likely to have higher mean SCORAD (p < 0.001), CCL17 (p < 0.001), CCL26/eotaxin-3 (p < 0.001), and eosinophil count (p < 0.001) than intrinsic AD patients. Predictive models for SCORAD identified CCL17, CCL27, serum total IgE, IL-33, and IL-5 as the most important predictors for SCORAD, but with weaker associations than single cytokines. Conclusions: Specific immunoinflammatory biomarkers in the serum, mainly of the Th2 pathway, are correlated with disease severity in patients with AD. Predictive models identified biomarkers associated with disease severity but this finding warrants further investigation.

scholarly journals Evaluation of serological methods for diagnosis of Puumala hantavirus infection (nephropathia epidemica).

1997 ◽  
Vol 35 (12) ◽  
pp. 3264-3268 ◽  
Author(s):  
K B Sjölander ◽  
F Elgh ◽  
H Kallio-Kokko ◽  
O Vapalahti ◽  
M Hägglund ◽  
...  
Keyword(s):  
Nephropathia Epidemica ◽  
Hantavirus Infection

scholarly journals How bank vole-PUUV interactions influence the eco-evolutionary processes driving nephropathia epidemica epidemiology: An experimental and genomic approach

2020 ◽  
Author(s):  
Sarah Madrières ◽  
Caroline Tatard ◽  
Séverine Murri ◽  
Johann Vulin ◽  
Maxime Galan ◽  
...  
Keyword(s):  
Bank Vole ◽  
Cross Infection ◽  
Nephropathia Epidemica ◽  
Puumala Virus ◽  
Serological Response ◽  
Mild Form ◽  
Bank Voles ◽  
Genomic Approach ◽  
Endemic Strain ◽  
Excretory Organs

AbstractIn Europe, Puumala virus (PUUV) is responsible for nephropathia epidemica (NE), a mild form of haemorrhagic fever with renal syndrome (HFSR). Despite the presence of its reservoir, the bank vole, on most of French territory, the geographic distribution of NE cases is heterogeneous and NE endemic and non-endemic areas have been reported. In this study we analyzed whether bank vole-PUUV interactions could partly shape these epidemiological differences. We performed crossed-experimental infections using wild bank voles from French endemic (Ardennes) and non-endemic (Loiret) areas, and two French PUUV strains isolated from these areas. The serological response and dynamics of PUUV infection were compared between the four cross-infection combinations. We showed that the serological response and the presence of PUUV in excretory organs were more important in bank voles infected with the PUUV endemic strain. Moreover, the within-host viral diversity in excretory organs was higher than in other non-excretory organs for the NE endemic cross-infection, but not for the NE non-endemic cross-infection. Altogether, our results showed that genetically different PUUV strains, and in a lesser extent their interaction with sympatric bank voles, could affect virus replication and diversity. This could impact PUUV excretion/transmission between rodents and to humans, and in turn at least partly shape NE epidemiology in France.

scholarly journals Human Cytomegalovirus Genome Diversity in Longitudinally Collected Breast Milk Samples

2021 ◽  
Vol 11 ◽  
Author(s):  
Jasper Götting ◽  
Katrin Lazar ◽  
Nicolás M. Suárez ◽  
Lars Steinbrück ◽  
Tabea Rabe ◽  
...  
Keyword(s):  
Breast Milk ◽  
Human Cytomegalovirus ◽  
High Throughput Sequencing ◽  
De Novo ◽  
Severe Disease ◽  
Viral Population ◽  
Preterm Neonates ◽  
Genotype Distribution ◽  
Milk Samples ◽  
Wide Range

Reactivation and shedding of human cytomegalovirus (HCMV) in breast milk during lactation is highly frequent in HCMV-seropositive mothers. This represents a key transmission route for postnatal HCMV infection and can lead to severe disease in preterm neonates. Little is known about HCMV strain composition or longitudinal intrahost viral population dynamics in breast milk from immunocompetent women. We performed HCMV-specific target enrichment and high-throughput sequencing of 38 breast milk samples obtained in Germany between days 10 and 60 postpartum from 15 mothers with HCMV DNA lactia, and assembled HCMV consensus sequences de novo. The genotype distribution and number of HCMV strains present in each sample were determined by quantifying genotype-specific sequence motifs in 12 hypervariable viral genes, revealing a wide range of genotypes (82/109) for these genes in the cohort and a unique, longitudinally stable strain composition in each mother. Reactivation of up to three distinct HCMV strains was detected in 8/15 of mothers, indicating that a representative subset of the woman’s HCMV reservoir might be locally reactivated early during lactation. As described previously, nucleotide diversity of samples with multiple strains was much higher than that of samples with single strains. Breast milk as a main source of postnatal mother-to-infant transmission may serve as a repository for viral diversity and thus play an essential role in the natural epidemiology of HCMV.

scholarly journals Association of the CCR5 gene with type 1 diabetes mellitus

2013 ◽  
Vol 59 (2) ◽  
pp. 3-6
Author(s):  
O I Kopylova ◽  
T L Kuraeva ◽  
E Iu Lavrikova ◽  
E V Titovich ◽  
A G Nikitin ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Type 1 Diabetes ◽  
Type 1 Diabetes Mellitus ◽  
Healthy Subjects ◽  
Significant Rise ◽  
Diabetic Patients ◽  
Ccr5 Gene ◽  
Base Pair Deletion ◽  
Time Amplification

Aim of the study. To elucidate the association between the polymorphous marker A/del132 of the CCR5 gene with type 1 diabetes mellitus. Materials and methods. The study included 177 patients with type 1 diabetes mellitus (DM1) and 408 healthy subjects (ethnic Russians). CR5 alleles and genotypes were identified with the use of the real-time amplification technique. Results. It was shown that the CCR5 allele without 32 base pair deletion (allele A) predominated in both diabetic patients and diabetes-free subjects. The difference between their occurrence in the two groups was insignificant. At the same time, we documented a significant rise in the frequency of del132/del132 genotype in the diabetic patients compared with the healthy subjects (p=0.008). It is concluded that carriers of the CCR5-del32/del32 genotype in the Russian population of Moscow are at high risk of developing type 1 diabetes mellitus.

scholarly journals Higher Circulating Concentration of Interleukin-38 in Patients with Knee Osteoarthritis: Its Association with Disease Severity

2021 ◽  
Author(s):  
Mitra Abassifard ◽  
Hossein Khorramdelazad ◽  
Shayan Rezaee ◽  
Abdollah Jafarzadeh
Keyword(s):  
Inflammatory Responses ◽  
Severe Disease ◽  
Serum Levels ◽  
Enzyme Linked Immunosorbent Assay ◽  
Control Group ◽  
Adaptive Immune ◽  
Valuable Marker ◽  
Vas Scores ◽  
Blood Specimens ◽  
Group Serum

Evidence showed that chronic inflammatory and immunopathological responses play a pivotal role in the development of osteoarthritis (OA). Interleukin-38 (IL-38) as a novel antiinflammatory cytokine with influential modulatory properties on both innate and adaptive immune responses can be involved in the pathogenesis of OA. Therefore, this study aimed to measure the serum level of IL-38 in OA patients to clarify the positive or negative association with disease and its severity. Blood specimens were collected from two groups including 23 newly-diagnosed OA patients and 22 healthy sex and age-matched subjects as a control group. Serum IL-38 quantities were measured using enzyme-linked immunosorbent assay (ELISA). Significantly higher IL-38 levels were detected in OA patients in comparison with the healthy group (265.78±41.27 pg/mL vs 44.23±6.04 pg/mL, p=0.0001). The IL-38 concentration in OA patients with Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) scores>40 and in OA patients with visual analog scale (VAS) scores>5 were higher than those with WOMAC scores<40, and VAS scores<5 (p=0.026 and p=0.035, respectively). The IL-38 levels in OA patients with body mass index (BMI)<25 were also significantly higher than in patients with BMI>25 (p=0.05). According to our findings, WOMAC, VAS, and BMI indices may influence the IL-38 serum levels in OA patients and it may be elevated in OA patients to modulate inflammatory responses in a compensatory manner. The patients with OA, especially those with more severe disease express higher serum amounts of IL-38. Accordingly, IL-38 may be considered as a valuable marker for OA.

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