scholarly journals Longitudinal characterisation of phagocytic and neutralisation functions of anti-Spike antibodies in plasma of patients after SARS-CoV-2 infection.

2021 ◽  
Author(s):  
Anurag Adhikari ◽  
Arunasingam Abayasingam ◽  
Chaturaka Rodrigo ◽  
David Agapiou ◽  
Elvis Pandzic ◽  
...  
Keyword(s):  
Inflammatory Responses ◽  
Severe Disease ◽  
Fc Receptors ◽  
Lectin Pathway ◽  
Heat Inactivation ◽  
Viral Immunity ◽  
Autologous Plasma ◽  
Effector Cells ◽  
Moderate Disease ◽  
Variable Contribution

Phagocytic responses by effector cells to antibody or complement-opsonised viruses have been recognized to play a key role in anti-viral immunity. These include antibody dependent cellular phagocytosis mediated via Fc-receptors, phagocytosis mediated by classically activated complement-fixing IgM or IgG1 antibodies and antibody independent phagocytosis mediated via direct opsonisation of viruses by complement products activated via the mannose-binding lectin pathway. Limited data suggest these phagocytic responses by effector cells may contribute to the immunological and inflammatory responses in SARS-CoV-2 infection, however, their development and clinical significance remain to be fully elucidated. In this cohort of 62 patients, acutely ill individuals were shown to mount phagocytic responses to autologous plasma-opsonised SARS-CoV-2 Spike protein-coated microbeads as early as 10 days post symptom onset. Heat inactivation of the plasma prior to use as an opsonin caused 77-95% abrogation of the phagocytic response, and pre-blocking of Fc-receptors on the effector cells showed only 18-60% inhibition. These results suggest that SARS-CoV-2 can provoke early phagocytosis, which is primarily driven by heat labile components, likely activated complements, with variable contribution from anti-Spike antibodies. During convalescence, phagocytic responses correlated significantly with anti-Spike IgG titers. Older patients and patients with severe disease had significantly higher phagocytosis and neutralisation functions when compared to younger patients or patients with asymptomatic, mild, or moderate disease. A longitudinal study of a subset of these patients over 12 months showed preservation of phagocytic and neutralisation functions in all patients, despite a drop in the endpoint antibody titers by more than 90%. Interestingly, surface plasmon resonance showed a significant increase in the affinity of the anti-Spike antibodies over time correlating with the maintenance of both the phagocytic and neutralisation functions suggesting that improvement in the antibody quality over the 12 months contributed to the retention of effector functions.

scholarly journals Pattern of inflammatory immune response determines the clinical course and outcome of COVID-19: unbiased clustering analysis

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Eunyoung Emily Lee ◽  
Kyoung-Ho Song ◽  
Woochang Hwang ◽  
Sin Young Ham ◽  
Hyeonju Jeong ◽  
...  
Keyword(s):  
Immune Response ◽  
Immune Responses ◽  
Clustering Analysis ◽  
Validation Cohort ◽  
Inflammatory Responses ◽  
Clinical Course ◽  
Severe Disease ◽  
Outcome Data ◽  
Inflammatory Immune Response ◽  
Cluster 2

AbstractThe objective of the study was to identify distinct patterns in inflammatory immune responses of COVID-19 patients and to investigate their association with clinical course and outcome. Data from hospitalized COVID-19 patients were retrieved from electronic medical record. Supervised k-means clustering of serial C-reactive protein levels (CRP), absolute neutrophil counts (ANC), and absolute lymphocyte counts (ALC) was used to assign immune responses to one of three groups. Then, relationships between patterns of inflammatory responses and clinical course and outcome of COVID-19 were assessed in a discovery and validation cohort. Unbiased clustering analysis grouped 105 patients of a discovery cohort into three distinct clusters. Cluster 1 (hyper-inflammatory immune response) was characterized by high CRP levels, high ANC, and low ALC, whereas Cluster 3 (hypo-inflammatory immune response) was associated with low CRP levels and normal ANC and ALC. Cluster 2 showed an intermediate pattern. All patients in Cluster 1 required oxygen support whilst 61% patients in Cluster 2 and no patient in Cluster 3 required supplementary oxygen. Two (13.3%) patients in Cluster 1 died, whereas no patient in Clusters 2 and 3 died. The results were confirmed in an independent validation cohort of 116 patients. We identified three different patterns of inflammatory immune response to COVID-19. Hyper-inflammatory immune responses with elevated CRP, neutrophilia, and lymphopenia are associated with a severe disease and a worse outcome. Therefore, targeting the hyper-inflammatory response might improve the clinical outcome of COVID-19.

scholarly journals Transcriptomic Analysis of Inbred Chicken Lines Reveals Infectious Bursal Disease Severity Is Associated with Greater Bursal Inflammation In Vivo and More Rapid Induction of Pro-Inflammatory Responses in Primary Bursal Cells Stimulated Ex Vivo

Viruses ◽  
2021 ◽  
Vol 13 (5) ◽  
pp. 933
Author(s):  
Amin S. Asfor ◽  
Salik Nazki ◽  
Vishwanatha R.A.P. Reddy ◽  
Elle Campbell ◽  
Katherine L. Dulwich ◽  
...  
Keyword(s):  
Rho Gtpases ◽  
Inflammatory Responses ◽  
Ex Vivo ◽  
Severe Disease ◽  
Infectious Bursal Disease ◽  
Rna Seq ◽  
Rapid Induction ◽  
Cytoskeletal Regulation ◽  
Bursal Disease

In order to better understand differences in the outcome of infectious bursal disease virus (IBDV) infection, we inoculated a very virulent (vv) strain into White Leghorn chickens of inbred line W that was previously reported to experience over 24% flock mortality, and three inbred lines (15I, C.B4 and 0) that were previously reported to display no mortality. Within each experimental group, some individuals experienced more severe disease than others but line 15I birds experienced milder disease based on average clinical scores, percentage of birds with gross pathology, average bursal lesion scores and average peak bursal virus titre. RNA-Seq analysis revealed that more severe disease in line W was associated with significant up-regulation of pathways involved in inflammation, cytoskeletal regulation by Rho GTPases, nicotinic acetylcholine receptor signaling, and Wnt signaling in the bursa compared to line 15I. Primary bursal cell populations isolated from uninfected line W birds contained a significantly greater percentage of KUL01+ macrophages than cells isolated from line 15I birds (p < 0.01) and, when stimulated ex vivo with LPS, showed more rapid up-regulation of pro-inflammatory gene expression than those from line 15I birds. We hypothesize that a more rapid induction of pro-inflammatory cytokine responses in bursal cells following IBDV infection leads to more severe disease in line W birds than in line 15I.

scholarly journals COVID-19 in Children: Expressions of Type I/II/III Interferons, TRIM28, SETDB1, and Endogenous Retroviruses in Mild and Severe Cases

2021 ◽  
Vol 22 (14) ◽  
pp. 7481
Author(s):  
Pier-Angelo Tovo ◽  
Silvia Garazzino ◽  
Valentina Daprà ◽  
Giulia Pruccoli ◽  
Cristina Calvi ◽  
...  
Keyword(s):  
Viral Infections ◽  
Severe Disease ◽  
Endogenous Retroviruses ◽  
Type I ◽  
Human Endogenous Retroviruses ◽  
Moderate Disease ◽  
Amplification Assay ◽  
Positive Correlations ◽  
Inducible Genes ◽  
Inflammatory Syndrome

Children with the new coronavirus disease 2019 (COVID-19) have milder symptoms and a better prognosis than adult patients. Several investigations assessed type I, II, and III interferon (IFN) signatures in SARS-CoV-2 infected adults, however no data are available for pediatric patients. RIM28 and SETDB1 regulate the transcription of multiple genes involved in the immune response as well as of human endogenous retroviruses (HERVs). Exogenous viral infections can trigger the activation of HERVs, which in turn can induce inflammatory and immune reactions. Despite the potential cross-talks between SARS-CoV-2 infection and TRIM28, SETDB1, and HERVs, information on their expressions in COVID-19 patients is lacking. We assessed, through a PCR real time Taqman amplification assay, the transcription levels of six IFN-I stimulated genes, IFN-II and three of its sensitive genes, three IFN-lIIs, as well as of TRIM28, SETDB1, pol genes of HERV-H, -K, and -W families, and of env genes of Syncytin (SYN)1, SYN2, and multiple sclerosis-associated retrovirus (MRSV) in peripheral blood from COVID-19 children nd in control uninfected subjects. Higher expression levels of IFN-I and IFN-II inducible genes were observed in 36 COVID-19-infected children with mild or moderate disease as compared to uninfected controls, whereas their concentrations decreased in 17 children with severe disease and in 11 with multisystem inflammatory syndrome (MIS-C). Similar findings were found for the expression of TRIM-28, SETDB1, and every HERV gene. Positive correlations emerged between the transcriptional levels of type I and II IFNs, TRIM28, SETDB1, and HERVs in COVID-19 patients. IFN-III expressions were comparable in each group of subjects. This preserved induction of IFN-λs could contribute to the better control of the infection in children as compared to adults, in whom IFN-III deficiency has been reported. The upregulation of IFN-I, IFN-II, TRIM28, SETDB1, and HERVs in children with mild symptoms, their declines in severe cases or with MIS-C, and the positive correlations of their transcription in SARS-CoV-2-infected children suggest that they may play important roles in conditioning the evolution of the infection.

1329 Can One Size Fit All: Is Laparoscopic Roux-En-Y Gastric Bypass the Best Bariatric Procedure for Treating Type 2 Diabetes Mellitus (T2DM)?

2021 ◽  
Vol 108 (Supplement_6) ◽  
Author(s):  
V Mahendran ◽  
P Ricart ◽  
S Robinson ◽  
A Perry ◽  
M Wadley
Keyword(s):  
Bariatric Surgery ◽  
Gastric Bypass ◽  
Retrospective Cohort ◽  
Severe Disease ◽  
Morbidly Obese ◽  
Disease Remission ◽  
Mild Disease ◽  
Moderate Disease ◽  
Remission Rates

Abstract Introduction Bariatric surgery produces superior weight loss and reversal of comorbidities in morbidly obese individuals compared to medical therapy alone. Laparoscopic Roux-en-Y gastric bypass (LRYGB) was traditionally considered to prolonged remission of T2DM compared to other procedures such as Laparoscopic Sleeve-Gastrectomy (LSG). But recently published studies seek to disprove this by emphasising on duration and severity of T2DM before surgery rather than the type of procedure. We aim to verify if the severity of T2DM and type of operation (LRYGB Vs LSG) influence remission rates. Method In this retrospective cohort study, 204 patients were diagnosed with T2DM pre-operatively and had undergone either LRYGB or LSG. We used the Individualised Metabolic Surgery Score (IMSS) tool to divide patients into mild, moderate, and severe categories. Results Results showed that of the 204 patients 15% (n = 31) had mild disease, 62%( n = 127) had moderate disease and 23% (n = 46) had severe disease. Remission rates in each category were as follows: Conclusions We agree that patients with longstanding and severe T2DM have low remission rates after bariatric surgery, probably due to diminished beta-cell reserve. It is in contrary to recent publications which recommend LSG over LRYGB in patients with severe disease. This evidence necessitates further prospective studies before deciding which is the best procedure for patients with severe and longstanding T2DM.

Role of Superantigens in Allergic Inflammation: Their Relationship to Allergic Rhinitis, Chronic Rhinosinusitis, Asthma, and Atopic Dermatitis

2018 ◽  
Vol 32 (6) ◽  
pp. 502-517 ◽  
Author(s):  
Nuray Bayar Muluk ◽  
Fazilet Altın ◽  
Cemal Cingi
Keyword(s):  
T Cells ◽  
Allergic Rhinitis ◽  
Atopic Dermatitis ◽  
Inflammatory Response ◽  
Chronic Rhinosinusitis ◽  
Inflammatory Responses ◽  
Immunoglobulin E ◽  
Severe Disease ◽  
Allergic Inflammation ◽  
Allergic Dermatitis

Objectives Our intention was to review all material published to date regarding superantigens (SAgs) and allergy from an otorhinolaryngological viewpoint to understand this association more clearly. Methods We identified all materials published mentioning both SAg and allergic rhinitis (AR), chronic sinusitis, asthma, and atopic dermatitis (AD) that are indexed on PubMed, Google, or the ProQuest Central databases. Results Staphylococcus aureus is a significant bacterial pathogen in humans and has the ability to produce enterotoxins with superantigenic features. The inflammatory response in allergy seen in both B cell and T cell may be attributed to SAgs. Sufferers of both allergic asthma with rhinitis and AR alone produce serological evidence of immunoglobulin E formation to SAgs produced by S. aureus. Perennial AR sufferers carry S. aureus more frequently and the presence of the organism within the nasal cavity may exacerbate perennial AR. SAg produced by S. aureus potentially worsens the asthmatic inflammatory response within the airway and may lead to the airways becoming hyperresponsive, as well as possibly activating T cells if asthmatic control is poor. Staphylococcal SAgs potentially increase the risk of developing chronic rhinosinusitis with nasal polyposis, additionally being a marker for more severe disease. If SAgs bring about chronic inflammatory responses in the nose and sinuses, then T cells excreting interferon-gamma may be a crucial mediator. In allergic dermatitis, S. aureus could be a key player in exacerbation of the condition. Even in younger pediatric patients with allergic dermatitis, allergic hypersensitivity to SAgs is frequent and may be a factor explaining how severe the condition becomes. Conclusion Just as SAgs are known to feature in many allergic conditions, they play their part in AR, chronic rhinosinusitis, asthma, and AD. Further research is required before the relationship between SAgs and allergy can be adequately explained.

scholarly journals Dermatology life quality index in psoriasis patients attending a tertiary care hospital: a study from North India

2020 ◽  
Vol 8 (9) ◽  
pp. 3277
Author(s):  
Faizan Younus Shah ◽  
Ifrah Shafat Kitab ◽  
Aaqib Aslam Shah ◽  
Faisal Younis Shah ◽  
Mohd Younus Shah ◽  
...  
Keyword(s):  
Quality Of Life ◽  
Severe Disease ◽  
Life Quality ◽  
Health Related Quality ◽  
Disease Group ◽  
Moderate Disease ◽  
Related Quality ◽  
Health Related ◽  
The Impact

Background: Psoriasis affects nearly 1% of the world population. It can be a source of significant morbidity and psychological stress to the patient but is not lethal under ordinary circumstances. Patients suffering from the disease feel a lack of empathy on part of care-givers, family members, healthcare professionals as well as society in general. Dermatology life quality index (DLQI) is a questionnaire-based assessment of health related quality of life in patients suffering from skin disorders and has been seen to correlate well with the impact of the disease on a patient. This study was done to understand the impact of psoriasis on the overall well-being of patients using DLQI as the tool of assessment.Methods: The study included 40 cases of psoriasis that were assessed for the severity of the disease based on percentage body surface area involvement. The impact of disease severity and other factors on the quality of life of the patient was assessed using DLQI.Results: Out of 35 patients with BSA involvement <50% (mild and moderate disease), 28.6% (n=10/35) showed a very large or extremely large effect on the quality of life while no patient with a BSA involvement >50% (severe and very severe disease) reported the same. A small, moderate or no effect on the DLQI was seen in 71.4% (n=25/35) of cases from the mild and moderate disease group while 100% (n=5/5) of cases from severe and very severe disease group reported a similar effect. Thus, DLQI was not directly related to the extent of BSA involvement and was dependent on other factors as well.Conclusion: Age had a correlation with the effect of the disease on the quality of life of psoriasis cases. Patients who were younger were more likely to report stress and anxiety related to the recurrences seen with the disease. Patients with lesions on sites that are socially exposed like face, hands, scalp, etc. were more likely to feel embarrassed about their condition. Younger age, female gender, lesions on exposed sites and recently diagnosed patients (<12 months) were factors which had a significant impact on the health-related quality of life of patients. The severity of disease and extent of involvement were not always directly related to extent of impact on the quality of life.

scholarly journals Transcriptomic analysis reveals that severity of infectious bursal disease in White Leghorn inbred chicken lines is associated with greater bursal inflammation in vivo and more rapid induction of pro-inflammatory responses in primary bursal cells stimulated ex vivo.

2021 ◽  
Author(s):  
Amin S Asfor ◽  
Salik Nazki ◽  
Vishwanatha RAP Reddy ◽  
Elle Campbell ◽  
Katherine L Dulwich ◽  
...  
Keyword(s):  
Rho Gtpases ◽  
Inflammatory Responses ◽  
Ex Vivo ◽  
Severe Disease ◽  
Infectious Bursal Disease ◽  
White Leghorn ◽  
Rapid Induction ◽  
Cytoskeletal Regulation ◽  
Bursal Disease

In order to better understand differences in the outcome of infectious bursal disease virus (IBDV) infection, we inoculated a very virulent (vv) strain into White Leghorn chickens of inbred line W that was previously reported to experience over 24% flock mortality, and three inbred lines (15I, C.B4 and 0) that were previously reported to display no mortality. Within each experimental group, some individuals experienced more severe disease than others but line 15I birds experienced milder disease based on average clinical scores, percentage of birds with gross pathology, average bursal lesion scores and average peak bursal virus titre. RNA-Seq analysis revealed that more severe disease in line W was associated with significant up-regulation of pathways involved in inflammation, cytoskeletal regulation by Rho GTPases, nicotinic acetylcholine receptor signaling, and Wnt signaling in the bursa compared to line 15I. Primary bursal cell populations isolated from uninfected line W birds contained a significantly greater percentage of KUL01+ macrophages than cells isolated from line 15I birds (p<0.01) and, when stimulated ex vivo with LPS, showed more rapid up-regulation of pro-inflammatory gene expression than those from line 15I birds. We hypothesize that a more rapid induction of pro-inflammatory cytokine responses in bursal cells following IBDV infection leads to more severe disease in line W birds than in line 15I.

Pathogenesis of rheumatoid arthritis

2013 ◽  
pp. 839-848
Author(s):  
Ranjeny Thomas ◽  
Andrew P. Cope
Keyword(s):  
Rheumatoid Arthritis ◽  
Inflammatory Responses ◽  
Disease Process ◽  
Cartilage Destruction ◽  
Effector Cells ◽  
Inflammatory Phase ◽  
Cellular Analysis ◽  
Genome Level ◽  
Inflammatory Milieu ◽  
Adaptive Immune Systems

In depth molecular and cellular analysis of synovial tissue and fluid from patients with rheumatoid arthritis has provided important insights into understanding disease pathogenesis. Advances in the 1980s and 1990s included modern cloning strategies, sensitive and specific assays for inflammatory mediators, production of high-affinity neutralizing monoclonal antibodies, advances in flow cytometry, and gene targeting and transgenic strategies in rodents. In the 21st century, technological platforms offer unparalleled opportunities for systematic and unbiased interrogation of the disease process at a whole-genome level. Here we describe the key molecular and cellular characteristics of the inflamed synovium and how infiltrating cells get there. With this background, we outline current concepts of the different phases of disease, how the first phase of genetic susceptibility evolves into autoimmunity, triggered by the exposome, prior to the onset of clinically apparent inflammatory disease. We then describe the pathways that actively contribute to this early inflammatory phase and document the key effector cells and molecules of the innate and adaptive immune systems that orchestrate and maintain chronic synovial inflammatory responses. We summarize how this inflammatory milieu translates to cartilage destruction and bone resorption in synovial joints, and conclude by reviewing those factors in inflamed synovium that promote immune homeostasis.

scholarly journals 2577. Periodontal Disease and the Oral Microbiome in Alcohol-Dependent Individuals

2019 ◽  
Vol 6 (Supplement_2) ◽  
pp. S895-S896
Author(s):  
Brianna K Meeks ◽  
Jen Barb ◽  
Sarah E Mudra ◽  
Narjis Kazmi ◽  
Ralph T S Tuason, ◽  
...  
Keyword(s):  
Periodontal Disease ◽  
Pathogenic Bacteria ◽  
Alveolar Bone ◽  
Severe Disease ◽  
Disease Status ◽  
Oral Microbiome ◽  
Moderate Disease ◽  
Rdna Sequencing ◽  
Severe Periodontitis ◽  
Alcohol Dependent

Abstract Background Periodontal disease results from a polymicrobial infection composed of pathogenic bacteria that colonize the oral cavity, resulting in loss of periodontal attachment and alveolar bone. Periodontitis can increase the risk or exacerbate other comorbidities. Alcohol use increases the risk of periodontitis, but there is little knowledge about periodontitis among people who misuse alcohol. Methods As part of a larger oral and gut microbiome study, this analysis examines the oral microbiome in the occurrence and severity of periodontitis among alcohol-dependent (AD) subjects undergoing a 28-day inpatient alcohol treatment program. Tongue brushings were collected from 22 subjects within the first week of admission, and 16S rDNA sequencing was performed. All subjects had a dental examination during the inpatient stay. This analysis divided periodontal disease status into three major groups–no disease, mild or moderate disease, and severe disease. One-way ANOVA was used to compare microbial genera across the 3 groups. Results Nineteen (86%) of the subjects had periodontitis: 16 had mild or moderate disease, and 3 had severe disease. Statistically different microbial genera in at least one of the three groups (P ≤ 0.05 corresponding to FDR ≤ 0.25) that had a relative abundance of at least 0.5% include: Bifidobacterium, Lactobacillus, Parvimonas, Peptostreptococcus, Porphyromonas, and Treponema. Surprisingly, the subjects with no periodontitis had increased abundances of genera that are often pathogens, Porphyromonas and Peptostreptococcus. Subjects with severe periodontitis had increased abundances of known pathogens Treponema and Parvimonas, as well as Lactobacillus, which has been associated with dental caries. Conclusion We observed that periodontitis accompanies chronic AD, given that 86% of our subjects had the disease. While some microbiome differences for individuals with and without periodontitis were not consistent with the existing literature, this may have many explanations. Future studies should consider how chronic AD could change the microbial ecology of the mouth and lead to further infection as well as utilizing multiple oral sites and a larger sample size to better understand the relationship between AD and periodontal disease. Intramural funds from NIH Disclosures All authors: No reported disclosures.

scholarly journals Physiology of Midkine and Its Potential Pathophysiological Role in COVID-19

2020 ◽  
Vol 11 ◽  
Author(s):  
Giulia Sanino ◽  
Martino Bosco ◽  
Giuseppe Terrazzano
Keyword(s):  
Inflammatory Responses ◽  
Pathological Condition ◽  
Severe Pneumonia ◽  
Immune Effector ◽  
Effector Cells ◽  
Coronary Syndrome ◽  
Clinical Complications ◽  
Mediators Of Inflammation ◽  
Autoimmune Conditions ◽  
Pathogen Clearance

SARS-CoV2 infection not only causes abnormal severe pneumonia but also induces other relevant pathophysiological effects on several tissues and organs. In this regard, the clinical complications observed in COVID-19 include acute coronary syndrome, pulmonary thromboembolism, myocarditis and, in the severe cases, the occurrence of disseminated intravascular coagulation. Literature on COVID-19 highlighted the central role of the Renin Angiotensin Aldosterone System in the determinism of SARS-CoV2 cellular internalization in the target tissues. Lung degeneration and respiratory distress appear to be dependent on the perturbance of physiological mechanisms, such as the uncontrolled release of pro-inflammatory cytokines, a dysregulation of the fibrinolytic coagulative cascade and the hyperactivation of immune effector cells. In this mini review, we address the physiology of Midkine, a growth factor able to bind heparin, and its pathophysiological potential role in COVID-19 determinism. Midkine increases in many inflammatory and autoimmune conditions and correlates with several dysfunctional immune-inflammatory responses that appear to show similarities with the pathophysiological elicited by SARS-CoV2. Midkine, together with its receptor, could facilitate the virus entry, fostering its accumulation and increasing its affinity with Ace2 receptor. We also focus on Netosis, a particular mechanism of pathogen clearance exerted by neutrophils, which under certain pathological condition becomes dysfunctional and can cause tissue damage. Moreover, we highlight the mechanism of autophagy that the new coronavirus could try to escape in order to replicate itself, as well as on pulmonary fibrosis induced by hypoxia and on the release of cytokines and mediators of inflammation, correlating the interplay between Midkine and SARS-CoV2.

Sign in / Sign up

Export Citation Format

Share Document