scholarly journals Immunoglobulin G1 Fc glycosylation as an early hallmark of severe COVID-19

2021 ◽  
Author(s):  
Tamas Pongracz ◽  
Jan Nouta ◽  
Wenjun Wang ◽  
Krista E. van Meijgaarden ◽  
Federica Linty ◽  
...  
Keyword(s):  
Disease Severity ◽  
Inflammatory Markers ◽  
Inflammatory Responses ◽  
Disease Onset ◽  
Disease Course ◽  
Total Plasma ◽  
Liquid Chromatography Mass Spectrometry ◽  
Disease Mechanism ◽  
Effector Functions ◽  
Research And Innovation

Background Immunoglobulin G1 (IgG1) effector functions are impacted by the structure of fragment crystallizable (Fc) tail-linked N-glycans. Low fucosylation levels on severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein specific (anti-S) IgG1 has been described as a hallmark of severe coronavirus disease 2019 (COVID-19) and may lead to activation of macrophages via immune complexes thereby promoting inflammatory responses, altogether suggesting involvement of IgG1 Fc glycosylation modulated immune mechanisms in COVID-19. Methods In this prospective, observational single center cohort study, IgG1 Fc glycosylation was analyzed by liquid chromatography - mass spectrometry following affinity capturing from serial plasma samples of 159 SARS-CoV-2 infected patients. Findings At baseline close to disease onset, anti-S IgG1 glycosylation was highly skewed when compared to total plasma IgG1. A rapid, general reduction in glycosylation skewing was observed during the disease course. Low anti-S IgG1 galactosylation and sialylation as well as high bisection were early hallmarks of disease severity, whilst high galactosylation and sialylation and low bisection were found in patients with low disease severity. In line with these observations, anti-S IgG1 glycosylation correlated with various inflammatory markers. Interpretation Association of low galactosylation, sialylation as well as high bisection with disease severity suggests that Fc-glycan modulated interactions contribute to disease mechanism. Further studies are needed to understand how anti-S IgG1 glycosylation may contributes to disease mechanism and to evaluate its biomarker potential. Funding This project received funding from the European Commission's Horizon2020 research and innovation program for H2020-MSCA-ITN IMforFUTURE, under grant agreement number 721815.

scholarly journals Bone mineral density and explanatory factors in children and adults with juvenile dermatomyositis at long term follow-up; a cross sectional study

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Henriette Schermacher Marstein ◽  
Kristin Godang ◽  
Berit Flatø ◽  
Ivar Sjaastad ◽  
Jens Bollerslev ◽  
...  
Keyword(s):  
Bone Turnover ◽  
Inflammatory Markers ◽  
Juvenile Dermatomyositis ◽  
Inflammatory Myopathy ◽  
Disease Onset ◽  
Whole Body ◽  
Mineral Density ◽  
Z Scores

Abstract Background Juvenile dermatomyositis (JDM) is the most common idiopathic inflammatory myopathy in children and adolescents. Both the disease and its treatment with glucocorticoids may negatively impact bone formation. In this study we compare BMD in patients (children/adolescence and adults) with long-standing JDM with matched controls; and in patients, explore how general/disease characteristics and bone turnover markers are associated with BMD. Methods JDM patients (n = 59) were examined median 16.8y (range 6.6–27.0y) after disease onset and compared with 59 age/sex-matched controls. Dual-energy X-ray absorptiometry (DXA) was used to measure BMD of the whole body and lumbar spine (spine) in all participants, and of ultra-distal radius, forearm and total hip in participants ≥20y only. Markers of bone turnover were analysed, and associations with outcomes explored. Results Reduced BMD Z-scores (<−1SD) were found in 19 and 29% of patients and 7 and 9% of controls in whole body and spine, respectively (p-values < 0.05). BMD and BMD Z-scores for whole body and spine were lower in all patients and for < 20y compared with their respective controls. In participants ≥20y, only BMD and BMD Z-score of forearm were lower in the patients versus controls. In patients, BMD Z-scores for whole body and/or spine were found to correlate negatively with prednisolone use at follow-up (yes/no) (age < 20y), inflammatory markers (age ≥ 20y) and levels of interferon gamma-induced protein 10 (IP-10) (both age groups). In all patients, prednisolone use at follow-up (yes/no) and age ≥ 20y were independent correlates of lower BMD Z-scores for whole body and spine, respectively. Conclusion In long-term JDM, children have more impairment of BMD than adults in spine and whole-body. Associations with BMD were found for both prednisolone and inflammatory markers, and a novel association was discovered with the biomarker of JDM activity, IP-10.

scholarly journals HPV Strain Predicts Severity of Juvenile-Onset Recurrent Respiratory Papillomatosis with Implications for Disease Screening

Cancers ◽  
2021 ◽  
Vol 13 (11) ◽  
pp. 2556
Author(s):  
Mary C. Bedard ◽  
Alessandro de Alarcon ◽  
Yann-Fuu Kou ◽  
David Lee ◽  
Alexandra Sestito ◽  
...  
Keyword(s):  
Gene Expression ◽  
Disease Severity ◽  
Disease Onset ◽  
Tissue Bank ◽  
Benign Neoplasm ◽  
Recurrent Respiratory Papillomatosis ◽  
Clinical Severity ◽  
Viral Gene ◽  
Juvenile Onset ◽  
Severity Scores

Juvenile-onset recurrent respiratory papillomatosis (JoRRP) is the most common benign neoplasm of the larynx in children, presenting with significant variation in clinical course and potential for progression to malignancy. Since JoRRP is driven by human papillomavirus (HPV), we evaluated viral factors in a prospective cohort to identify predictive factors of disease severity. Twenty children with JoRRP undergoing routine debridement of papillomas were recruited and followed for ≥1 year. Demographical features, clinical severity scores, and surgeries over time were tabulated. Biopsies were used to establish a tissue bank and primary cell cultures for HPV6 vs. HPV11 genotyping and evaluation of viral gene expression. We found that patients with HPV11+ disease had an earlier age at disease onset, higher frequency of surgeries, increased number of lifetime surgeries, and were more likely to progress to malignancy. However, the amplitude of viral E6/E7 gene expression did not account for increased disease severity in HPV11+ patients. Determination of HPV strain is not routinely performed in the standard of care for JoRRP patients; we demonstrate the utility and feasibility of HPV genotyping using RNA-ISH for screening of HPV11+ disease as a biomarker for disease severity and progression in JoRRP patients.

scholarly journals Relationships of gut microbiota, short-chain fatty acids, inflammation, and the gut barrier in Parkinson’s disease

2021 ◽  
Vol 16 (1) ◽  
Author(s):  
Velma T. E. Aho ◽  
Madelyn C. Houser ◽  
Pedro A. B. Pereira ◽  
Jianjun Chang ◽  
Knut Rudi ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Fatty Acids ◽  
Parkinson's Disease ◽  
Gut Microbiota ◽  
Inflammatory Responses ◽  
Disease Onset ◽  
Short Chain Fatty Acids ◽  
Short Chain ◽  
Dependent Manner ◽  
Chain Fatty Acids

Abstract Background Previous studies have reported that gut microbiota, permeability, short-chain fatty acids (SCFAs), and inflammation are altered in Parkinson’s disease (PD), but how these factors are linked and how they contribute to disease processes and symptoms remains uncertain. This study sought to compare and identify associations among these factors in PD patients and controls to elucidate their interrelations and links to clinical manifestations of PD. Methods Stool and plasma samples and clinical data were collected from 55 PD patients and 56 controls. Levels of stool SCFAs and stool and plasma inflammatory and permeability markers were compared between patients and controls and related to one another and to the gut microbiota. Results Calprotectin was increased and SCFAs decreased in stool in PD in a sex-dependent manner. Inflammatory markers in plasma and stool were neither intercorrelated nor strongly associated with SCFA levels. Age at PD onset was positively correlated with SCFAs and negatively correlated with CXCL8 and IL-1β in stool. Fecal zonulin correlated positively with fecal NGAL and negatively with PD motor and non-motor symptoms. Microbiota diversity and composition were linked to levels of SCFAs, inflammatory factors, and zonulin in stool. Certain relationships differed between patients and controls and by sex. Conclusions Intestinal inflammatory responses and reductions in fecal SCFAs occur in PD, are related to the microbiota and to disease onset, and are not reflected in plasma inflammatory profiles. Some of these relationships are distinct in PD and are sex-dependent. This study revealed potential alterations in microbiota-host interactions and links between earlier PD onset and intestinal inflammatory responses and reduced SCFA levels, highlighting candidate molecules and pathways which may contribute to PD pathogenesis and clinical presentation and which warrant further investigation.

scholarly journals Neopterin predicts disease severity in hospitalized patients with COVID-19

2020 ◽  
Author(s):  
Rosa Bellmann-Weiler ◽  
Lukas Lanser ◽  
Francesco Burkert ◽  
Stefanie Seiwald ◽  
Gernot Fritsche ◽  
...  
Keyword(s):  
Mechanical Ventilation ◽  
Retrospective Analysis ◽  
Disease Severity ◽  
Predictive Value ◽  
Clinical Management ◽  
Inflammatory Markers ◽  
Predictive Marker ◽  
Hospitalized Patients ◽  
Icu Admission ◽  
Circulating Inflammatory Markers

Abstract This study evaluates the predictive value of circulating inflammatory markers, especially neopterin, in patients with COVID-19. Within this retrospective analysis of 115 hospitalized COVID-19 patients, elevated neopterin levels upon admission were significantly associated with disease severity, risk for ICU admission, need for mechanical ventilation and death. Therefore, neopterin is a reliable predictive marker in patients with COVID-19 and may help to improve the clinical management of patients.

scholarly journals Grade of esophageal cancer and nutritional status impact on postsurgery outcomes

2010 ◽  
Vol 47 (4) ◽  
pp. 348-353 ◽  
Author(s):  
Flávia Andréia Marin ◽  
Vânia Cristina Lamônica-Garcia ◽  
Maria Aparecida Coelho de Arruda Henry ◽  
Roberto Carlos Burini
Keyword(s):  
Body Mass Index ◽  
Nutritional Status ◽  
Disease Severity ◽  
Body Mass ◽  
Disease Onset ◽  
Body Weight Loss ◽  
Blood Chemistry ◽  
Palliative Surgery ◽  
Postsurgical Complications ◽  
Complications And Mortality

CONTEXT: Undernutrition is a well known underlying cause in both disease onset and outcome. OBJECTIVE: To associate disease severity with pre surgical nutritional status, the main postsurgical complications, and mortality in esophagus cancer patients. METHOD: Retrospective data from 100 patients (38-81 years old, 85% males) who had undergone esophagectomy (G1/n = 25) or gastro/jejunostomy (G2/n = 75) between 1995 and 2004. Data included clinical, endoscopic, histological (TNM-UICC), dietary, anthropometric, blood chemistry, and postsurgical (>30 days) complications and mortality. Surgical groups were compared by Student's test and existing associations between variables by either c² or Fisher exact tests with P = 0.05. RESULTS: The studied sample was predominantly male (85%), white (80%), smokers and alcoholics (95%), dysphagics (95%) mostly presenting body weight loss before cancer diagnosis (78%). TNM III and IV predominated over I and II, associated (P<0.005) with higher body mass index and hypoalbuminemia (<3.5 mg/dL) frequency. Esophagic obstructions (n = 77) were associated (P = 0.002) with lower body mass index (kg/m²). Postsurgical complications were more common in G1 (69.2%) than G2, predominantly with infections in G2 (80%) and pleura-pulmonary in G1 (61%). Body mass index and lower lymphocyte counts were associated with early infections and postsurgical complications in G2. Plasma albumin levels were lower in this group than G1, and were associated with postsurgical complications and mortality whereas lower lymphocyte counts was associated with mortality in G1. CONCLUSIONS: Disease severity (or late diagnosis) is associated with poor nutritional status and palliative surgery which lead to more complicated postsurgery outcome and mortality. Early diagnosis and nutritional intervention are the recommended actions.

scholarly journals A clinical staging proposal of the disease course over time in non-severe patients with coronavirus disease 2019

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Yiting Lin ◽  
Yiqun Wu ◽  
Ping Zhong ◽  
Bingbo Hou ◽  
Jielan Liu ◽  
...  
Keyword(s):  
Inflammatory Markers ◽  
Clinical Signs ◽  
Clinical Staging ◽  
Disease Course ◽  
Prodromal Phase ◽  
The Third ◽  
Convalescent Phase ◽  
Secondary Damage ◽  
Remission Phase ◽  
Over Time

AbstractInformation on the clinical staging of coronavirus disease 2019 (COVID-19) is still limited. This study aimed to propose a clinical staging proposal of the disease course in non-severe patients with COVID-19. In this retrospective study, 108 non-severe patients with COVID-19 were grouped according to the duration from symptoms onset to hospital admission: ≤ 1 week, > 1 to 2 weeks, > 2 to 3 weeks, > 3 to 5 weeks, respectively. The dynamic changes of clinical signs were profiled across the four groups. A clinical staging proposal of the disease course over time was proposed from the perspective of the interaction between the virus and host. The prodromal phase, characterized by pneumonia, significant lymphopenia, and slightly elevated inflammatory markers, occurred in the first week after symptoms onset. In the second week, all the hematological and inflammatory markers were at the peak or bottom. Meanwhile, progressive pneumonia as well as the secondary damage of other organs (e.g. cardiac damage, coagulopathy, etc.) was significant during this period, making the disease progress into the apparent manifestation phase. In the third week, the improvement of the majority of clinical signs accompanied by a relatively high degree of inflammatory response defined the remission phase. After 3 weeks, patients were in the convalescent phase, in which all the indicators were maintained at a relatively normal level. We concluded that the disease course over time in non-severe patients with COVID-19 could be divided into four phases: the prodromal phase (in the first week), the apparent manifestation phase (in the second week), the remission phase (in the third week), and the convalescent phase (after 3 weeks), respectively. In clinical practice, tailored therapies should be considered seriously in different stages of the disease course.

scholarly journals Sex-Bias in Irritable Bowel Syndrome: Linking Steroids to the Gut-Brain Axis

2021 ◽  
Vol 12 ◽  
Author(s):  
Sik Yu So ◽  
Tor C. Savidge
Keyword(s):  
Irritable Bowel Syndrome ◽  
Sex Steroids ◽  
Disease Onset ◽  
Gastrointestinal Disorder ◽  
Underlying Disease ◽  
Disease Mechanism ◽  
Psychological Conditions ◽  
Nervous System Function ◽  
Irritable Bowel ◽  
Insight Into

Irritable bowel syndrome (IBS) is a functional gastrointestinal disorder that is more common in females. Despite its high global incidence, the disease mechanism is still unclear and therapeutic options remain limited. The sexual dimorphism in IBS incidence suggests that sex steroids play a role in disease onset and symptoms severity. This review considers sex steroids and their involvement in IBS symptoms and the underlying disease mechanisms. Estrogens and androgens play important regulatory roles in IBS symptomology, including visceral sensitivity, gut motility and psychological conditions, possibly through modulating the gut-brain axis. Steroids are regulators of hypothalamic-pituitary-adrenal activity and autonomic nervous system function. They also modulate gut microbiota and enteric nervous systems, impacting serotonin and mast cell signaling. Sex steroids also facilitate bidirectional cross-talk between the microbiota and host following bacterial transformation and recycling of steroids by the intestine. The sex-specific interplay between sex steroids and the host provides neuroendocrinology insight into the pathophysiology, epigenetics and treatment of IBS patients.

scholarly journals The Fc-mediated effector functions of a potent SARS-CoV-2 neutralizing antibody, SC31, isolated from an early convalescent COVID-19 patient, are essential for the optimal therapeutic efficacy of the antibody

PLoS ONE ◽  
2021 ◽  
Vol 16 (6) ◽  
pp. e0253487
Author(s):  
Conrad E. Z. Chan ◽  
Shirley G. K. Seah ◽  
De Hoe Chye ◽  
Shane Massey ◽  
Maricela Torres ◽  
...  
Keyword(s):  
Therapeutic Efficacy ◽  
Neutralizing Antibodies ◽  
Inflammatory Responses ◽  
Therapeutic Potential ◽  
Rhesus Macaques ◽  
Neutralizing Antibody ◽  
Effector Functions ◽  
Viral Loads ◽  
Therapeutic Doses ◽  
Dose Dependent

Although SARS-CoV-2-neutralizing antibodies are promising therapeutics against COVID-19, little is known about their mechanism(s) of action or effective dosing windows. We report the generation and development of SC31, a potent SARS-CoV-2 neutralizing antibody, isolated from a convalescent patient. Antibody-mediated neutralization occurs via an epitope within the receptor-binding domain of the SARS-CoV-2 Spike protein. SC31 exhibited potent anti-SARS-CoV-2 activities in multiple animal models. In SARS-CoV-2 infected K18-human ACE2 transgenic mice, treatment with SC31 greatly reduced viral loads and attenuated pro-inflammatory responses linked to the severity of COVID-19. Importantly, a comparison of the efficacies of SC31 and its Fc-null LALA variant revealed that the optimal therapeutic efficacy of SC31 requires Fc-mediated effector functions that promote IFNγ-driven anti-viral immune responses, in addition to its neutralization ability. A dose-dependent efficacy of SC31 was observed down to 5mg/kg when administered before viral-induced lung inflammatory responses. In addition, antibody-dependent enhancement was not observed even when infected mice were treated with SC31 at sub-therapeutic doses. In SARS-CoV-2-infected hamsters, SC31 treatment significantly prevented weight loss, reduced viral loads, and attenuated the histopathology of the lungs. In rhesus macaques, the therapeutic potential of SC31 was evidenced through the reduction of viral loads in both upper and lower respiratory tracts to undetectable levels. Together, the results of our preclinical studies demonstrated the therapeutic efficacy of SC31 in three different models and its potential as a COVID-19 therapeutic candidate.

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