Anti-DSF70 zur Differenzierung der Genese von interstitiellen Lungenerkrankungen

2020 ◽  
Vol 8 (2) ◽  
pp. 78-79
Author(s):  
Nicolas Kahn
Keyword(s):  
Interstitial Pneumonia ◽  
Connective Tissue Diseases ◽  
Healthy Individuals ◽  
Serum Samples ◽  
Inflammatory Conditions ◽  
Antibody Positivity ◽  
Nonspecific Interstitial Pneumonia ◽  
Negative Controls

Background: Anti-DFS70 antibodies, corresponding to the dense fine speckled antinuclear antibody (ANA) pattern in HEp-2 substrates, have been observed in chronic inflammatory conditions, cancer and in healthy individuals but in only a small percentage of patients with connective tissue diseases (CTD). Objectives: The study was aimed to investigate the possible role of anti-DFS70 antibodies to distinguish CTD associated interstitial lung disease (CTD-ILD) from idiopathic interstitial pneumonia (IIP) and to explore potential correlations between anti-DFS70 antibodies and clinical parameters. Methods: Serum samples were collected from 49 healthy controls (HC), 35 scleroderma-ILD (SSc-ILD) patients as negative controls for anti-DFS70 antibody, and 260 patients with the initial diagnosis IIP including 100 nonspecific interstitial pneumonia (NSIP) and 160 idiopathic pulmonary fibrosis (IPF) patients. ANA pattern was identified by indirect immunofluorescence on HEp-2 cells and anti-DFS70 antibodies were measured in serum by ELISA. Results: Serum anti-DFS70 antibodies were less frequently seen in ILD and SSc-ILD patients compared to HCs. Thirty-seven patients (34 initial idiopathic NSIP and 3 initial IPF patients) developed CTD during 24 months of follow-up, most of them combined with ANA positivity and anti-DFS70 antibody negativity. Anti-DFS70 antibody positivity was not significantly different between CTD-ILD and idiopathic ILD. Conclusions: The frequency of serum anti-DFS70 antibody is markedly decreased in patients with ILDs. Anti-DFS70 antibodies may be useful to predict CTD development in ILD patients.

scholarly journals Nonspecific interstitial pneumonia: survival is influenced by the underlying cause

2014 ◽  
Vol 45 (3) ◽  
pp. 746-755 ◽  
Author(s):  
Hilario Nunes ◽  
Kirsten Schubel ◽  
Diane Piver ◽  
Eline Magois ◽  
Séverine Feuillet ◽  
...  
Keyword(s):  
Interstitial Pneumonia ◽  
Cox Model ◽  
Connective Tissue Diseases ◽  
Rank Test ◽  
Log Rank Test ◽  
Kaplan Meier ◽  
Clinical Disorders ◽  
Nonspecific Interstitial Pneumonia ◽  
Better Than

Idiopathic, nonspecific interstitial pneumonia (NSIP) is most often associated with various clinical disorders, including connective tissue diseases (CTDs) and chronic hypersensitivity pneumonitis (cHP). Emerging evidence also suggests that “idiopathic” NSIP may be the lung manifestation of undifferentiated CTD (UCTD). However, whether or not NSIP outcome is influenced by the underlying cause remains uncertain.This retrospective study included 127 biopsy-proven NSIP patients (65 women, mean±sd age 55±12 years). Survivals were estimated using a Kaplan–Meier curve and compared using the log-rank test. Multivariate analyses were based on a Cox model.15 (11.8%) patients had cHP, 29 (22.8%) had CTD, 32 (25.2%) satisfied the Kinder criteria for UCTD and 51 (40.1%) had idiopathic NSIP. At the end of follow-up (mean±sd 64±54 months), a difference in survival was observed between aetiological groups (p=0.002). Survival was better for UCTD than for idiopathic NSIP (p=0.020) and similar to that observed for CTD. cHP survival tended to be poorer than that of idiopathic NSIP (p=0.087) and was an independent predictor of mortality (hazard ratio 2.17, 95% CI 1.05–4.47; p=0.035).NSIP outcome is influenced by its cause. cHP exhibits the highest mortality. UCTD does not differ from CTD supporting the concept of autoimmune NSIP, with a prognosis that is better than that of idiopathic NSIP.

Nonspecific Interstitial Pneumonia

2020 ◽  
Vol 41 (02) ◽  
pp. 184-201 ◽  
Author(s):  
Alan K. Y. Teoh ◽  
Tamera J. Corte
Keyword(s):  
Interstitial Pneumonia ◽  
Connective Tissue Diseases ◽  
Close Monitoring ◽  
Immunomodulatory Agents ◽  
Complex Disorder ◽  
Therapeutic Landscape ◽  
Separate Clinical Entity ◽  
Progression Of Disease ◽  
Nonspecific Interstitial Pneumonia

AbstractNonspecific interstitial pneumonia (NSIP) is a complex disorder commonly associated with other conditions such as connective tissue diseases (CTDs) and environmental exposures. Although idiopathic NSIP has been recognized as a separate clinical entity, recent studies have suggested that a proportion of these cases have autoimmune features suggestive of underlying CTDs. The diagnosis of NSIP usually carries a better prognosis compared with idiopathic pulmonary fibrosis but has an unpredictable natural history. Its pathogenesis is thought to be an inflammatory-driven process involving multiple pathways, including a genetic predisposition. The lack of specific clinical features often makes the diagnosis of NSIP difficult. The huge variability of radiological and histological features seen in NSIP adds to the complexity of achieving an accurate diagnosis of NSIP and a multidisciplinary approach is often required. There is a lack of consensus on the optimal management strategy of NSIP. Early clarification of the goals of therapy and close monitoring for the progression of disease is important across the spectrum of NSIP irrespective of its etiology. Although immunosuppressive and immunomodulatory agents are commonly used for severe and progressive disease, the therapeutic landscape of NSIP is constantly evolving as the role of newer agents such as antifibrotic therapies is being explored.

HYPOTHYROIDISM IN PREGNANCY -SIGNIFICANCE OF ADEQUATE TREATMENT: A STUDY OF 100 CASES IN NORTH BIHAR

2021 ◽  
pp. 40-41
Author(s):  
Vasudha Rani ◽  
Punam Kumari
Keyword(s):  
Post Partum ◽  
Adverse Outcomes ◽  
Endocrine Disorders ◽  
Potential Threat ◽  
Adequate Treatment ◽  
Antibody Positivity ◽  
Prompt Diagnosis ◽  
In Pregnancy

Pregnancy is a nature's gift of humanity for procreation and continuation of its race. This gift is however fraught with several complications and has potential threat to the mother and the foetus. When pregnancy is compounded by endocrine disorders such as hypothyroidism, the potential for maternal and foetal adverse outcomes can be immense. While a lot of attention has been focused on the adverse foetal outcomes consequent to hypothyroidism, attention is also being gradually directed towards the adverse maternal outcomes of this disorder. Role of antibody positivity in inuencing outcomes in a euthyroid woman, also needs further clarication. Prompt diagnosis and treatment of hypothyroidism in pregnancy is very essential. Subclinical hypothyroidism also needs to be detected and treated to prevent adverse outcomes, especially maternal. Since women with hypothyroidism during pregnancy, especially of the autoimmune variety might have a are up of the disorder post-partum, or might continue to require thyroxine replacement post-partum, adequate follow-up is mandatory. While targeted case nding is generally practised, recent evidence seems to indicate that universal screening might be a better option. In conclusion, routine screening, early conrmation of diagnosis and prompt treatment allied with regular post-partum follow up, is required to ensure favourable maternal and foetal outcomes.

scholarly journals Zika Virus Serologic Diagnosis by NS1 ELISA in Curacao

2017 ◽  
Vol 4 (suppl_1) ◽  
pp. S302-S303 ◽  
Author(s):  
Samantha Manuel ◽  
Liane Virginia-Cova ◽  
Loubiela Joseph ◽  
Chris Roggeveen ◽  
Radjin Steingrover
Keyword(s):  
Zika Virus ◽  
Cross Reactivity ◽  
Pregnant Female ◽  
Serum Samples ◽  
Zikv Infection ◽  
Igm Elisa ◽  
Pcr Diagnosis ◽  
Two Samples ◽  
Negative Controls

Abstract Background Zika virus (ZIKV) was introduced in the Caribbean island of Curacao in January 2016. A commercially available ZIKV IgM and IgG ELISA was evaluated on patients that were PCR-positive for ZIKV. Methods ZIKV infection was established by PCR in urine samples. Samples from PCR-positive patients were selected for validation of a ZIKV NS1 IgG and IgM ELISA. Patients with a follow-up sample ≥ 2 weeks after initial presentation were used to assess the sensitivity of the assay. Samples of 15 historical controls with serological evidence of Dengue, Chikungunya or an unrelated viral infection were included to establish specificity and cross-reactivity. Results Fourteen patients with positive ZIKV PCR diagnosis had repeated serum samples drawn ≥ 2 weeks after the initial sample. The combined results of these repeated IgM and IgG tests resulted in a sensitivity of 92%. One pregnant female showed no presence of IgG or IgM in any of the two samples. Testing of the panel of historical ZIKV-negative controls resulted in a specificity of 100% in both the quantitative and semi-quantitative setting of the ELISA. One patient with known high-titers of antibodies against Chikungunya virus in the respective panel displayed borderline reactive results for ZIKV IgG in both quantitative and semi-quantitative setting of the assay. Conclusion In this PCR-positive ZIKV cohort of patients, the newly available ZIKV NS1 ELISA displayed excellent performance characteristics. Cross-reactivity was indicated for Chikungunya in one case. No cross-reactivity was found for Dengue virus infection. One pregnant female showed no signs of developing anti-ZIKV IgM or IgG in this study. In the light of intrauterine pathogenesis, the lack of development of maternal IgG during ZIKV infection is a concern. Disclosures All authors: No reported disclosures.

scholarly journals Inhibition of microRNA-155 Protects Retinal Function Through Attenuation of Inflammation in Retinal Degeneration

2020 ◽  
Author(s):  
Riemke Aggio-Bruce ◽  
Joshua A. Chu-Tan ◽  
Yvette Wooff ◽  
Adrian V. Cioanca ◽  
Ulrike Schumann ◽  
...  
Keyword(s):  
Oxidative Damage ◽  
Retinal Degeneration ◽  
Ganglion Cells ◽  
Retinal Function ◽  
Retinal Ganglion ◽  
Retinal Tissue ◽  
Inflammatory Conditions ◽  
Retinal Degenerative Diseases ◽  
Negative Controls

Abstract Although extensively investigated in inflammatory conditions, the role of pro-inflammatory microRNAs (miRNAs), miR-155 and miR-146a, has not been well-studied in retinal degenerative diseases. We therefore aimed to explore the role and regulation of these miRNA in the degenerating retina, with a focus on miR-155. C57BL/6J mice were subjected to photo-oxidative damage for up to 5 days to induce focal retinal degeneration. MiR-155 expression was quantified by qRT-PCR in whole retina, serum, and small-medium extracellular vesicles (s-mEVs), and a PrimeFlow™ assay was used to identify localisation of miR-155 in retinal cells. Constitutive miR-155 knockout (KO) mice and miR-155 and miR-146a inhibitors were utilised to determine the role of these miRNA in the degenerating retina. Electroretinography was employed as a measure of retinal function, while histological quantification of TUNEL+ and IBA1+ positive cells was used to quantify photoreceptor cell death and infiltrating immune cells, respectively. Upregulation of miR-155 was detected in retinal tissue, serum and s-mEVs in response to photo-oxidative damage, localising to the nucleus of a subset of retinal ganglion cells and glial cells and in the cytoplasm of photoreceptors. Inhibition of miR-155 showed increased function from negative controls and a less pathological pattern of IBA1+ cell localisation and morphology at 5 days photo-oxidative damage. While neither dim-reared nor damaged miR-155 KO animals showed retinal histological difference from controls, following photo-oxidative damage, miR-155 KO mice showed increased a-wave relative to controls. We therefore consider miR-155 to be associated with the inflammatory response of the retina in response to photoreceptor-specific degeneration.

scholarly journals Role of Antilipopolysaccharide Antibodies in Serum Bactericidal Activity against Salmonella enterica Serovar Typhimurium in Healthy Adults and Children in the United States

2013 ◽  
Vol 20 (10) ◽  
pp. 1491-1498 ◽  
Author(s):  
Estela Trebicka ◽  
Susan Jacob ◽  
Waheed Pirzai ◽  
Bryan P. Hurley ◽  
Bobby J. Cherayil
Keyword(s):  
United States ◽  
Bactericidal Activity ◽  
Salmonella Enterica ◽  
The United States ◽  
Healthy Children ◽  
Healthy Individuals ◽  
Serum Samples ◽  
Content Type ◽  
Serovar Typhimurium

ABSTRACTRecent observations from Africa have rekindled interest in the role of serum bactericidal antibodies in protecting against systemic infection withSalmonella entericaserovar Typhimurium. To determine whether the findings are applicable to other populations, we analyzed serum samples collected from healthy individuals in the United States. We found that all but 1 of the 49 adult samples tested had robust bactericidal activity againstS. Typhimurium in a standardin vitroassay. The activity was dependent on complement and could be reproduced by immunoglobulin G (IgG) purified from the sera. The bactericidal activity was inhibited by competition with soluble lipopolysaccharide (LPS) fromS. Typhimurium but not fromEscherichia coli, consistent with recognition of a determinant in the O-antigen polysaccharide. Sera from healthy children aged 10 to 48 months also had bactericidal activity, although it was significantly less than in the adults, correlating with lower levels of LPS-specific IgM and IgG. The lone sample in our collection that lacked bactericidal activity was able to inhibit killing ofS. Typhimurium by the other sera. The inhibition correlated with the presence of an LPS-specific IgM and was associated with decreased complement deposition on the bacterial surface. Our results indicate that healthy individuals can have circulating antibodies to LPS that either mediate or inhibit killing ofS. Typhimurium. The findings contrast with the observations from Africa, which linked bactericidal activity to antibodies against anS. Typhimurium outer membrane protein and correlated the presence of inhibitory anti-LPS antibodies with human immunodeficiency virus infection.

scholarly journals Ageing Investigation Using Two-Time-Point Metabolomics Data from KORA and CARLA Studies

Metabolites ◽  
2019 ◽  
Vol 9 (3) ◽  
pp. 44 ◽  
Author(s):  
Choiwai Chak ◽  
Maria Lacruz ◽  
Jonathan Adam ◽  
Stefan Brandmaier ◽  
Marcela Covic ◽  
...  
Keyword(s):  
Smoking Status ◽  
Chronological Age ◽  
Healthy Individuals ◽  
Serum Samples ◽  
Metabolomics Data ◽  
Generalized Estimation Equation ◽  
And Oxidative Stress ◽  
Time Point

Ageing, one of the largest risk factors for many complex diseases, is highly interconnected to metabolic processes. Investigating the changes in metabolite concentration during ageing among healthy individuals offers us unique insights to healthy ageing. We aim to identify ageing-associated metabolites that are independent from chronological age to deepen our understanding of the long-term changes in metabolites upon ageing. Sex-stratified longitudinal analyses were performed using fasting serum samples of 590 healthy KORA individuals (317 women and 273 men) who participated in both baseline (KORA S4) and seven-year follow-up (KORA F4) studies. Replication was conducted using serum samples of 386 healthy CARLA participants (195 women and 191 men) in both baseline (CARLA-0) and four-year follow-up (CARLA-1) studies. Generalized estimation equation models were performed on each metabolite to identify ageing-associated metabolites after adjusting for baseline chronological age, body mass index, physical activity, smoking status, alcohol intake and systolic blood pressure. Literature researches were conducted to understand their biochemical relevance. Out of 122 metabolites analysed, we identified and replicated five (C18, arginine, ornithine, serine and tyrosine) and four (arginine, ornithine, PC aa C36:3 and PC ae C40:5) significant metabolites in women and men respectively. Arginine decreased, while ornithine increased in both sexes. These metabolites are involved in several ageing processes: apoptosis, mitochondrial dysfunction, inflammation, lipid metabolism, autophagy and oxidative stress resistance. The study reveals several significant ageing-associated metabolite changes with two-time-point measurements on healthy individuals. Larger studies are required to confirm our findings.

Follow-up evaluation of outliers with elevated spermine-spermidine acetyltransferase-1 activity.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e14536-e14536
Author(s):  
Andrew W. Maksymiuk ◽  
Paramjit S. Tappia ◽  
Bram Ramjiawan ◽  
Nazrina Khatun ◽  
Rahnuma Parveen ◽  
...  
Keyword(s):  
Liver Disease ◽  
Urinary Concentration ◽  
Malignant Neoplasms ◽  
Inflammatory Conditions ◽  
Mass Spec ◽  
Normal Individuals ◽  
Neoplastic Change ◽  
Diagnosis Of Lung Cancer

e14536 Background: In the evolving role of biomarkers, proteinomic signatures related to up-regulation of polyamine synthesis including spermine/spermidine acetyltransferase-1 (SSAT-1) appear to be promising markers of malignancy. Acetylamantadine (AA) excretion, a measure of SSAT-1 up-regulation, has been shown to be a marker for malignant proliferation. In preliminary analyses of ostensibly normal individuals from Canada (Winnipeg) and Bangladesh (Dhaka), a proportion were identified to have evidence of SSAT-1 up-regulation above the expected non-malignant range (outliers). These outliers were assessed and followed for development of identifiable medical conditions. Methods: SSAT-1 up regulation was assessed in 60 ostensibly normal individuals by analysis of urinary excretion of AA after ingestion of amantadine 200 mg x 1 dose. AA was assayed using HPLC-mass spec techniques as previously described. Outliers who consented were followed-up by clinical examinations, routine biochemical and hematological tests and radiographs, where indicated. Results: Total AA average (median) excretion at 6 hrs in the Winnipeg cohort was 579+/-252 vs 1699+/-633 ng in the Dhaka cohort. Average urinary concentration at 6 hrs was 3.75+/-0.75 vs 21+/-20 ng/ml. In outliers consenting to follow-up, 1 case of invasive malignancy was identified, 6 cases of pre-malignant neoplastic change, chronic liver disease in 7 cases and chronic inflammation in 2 cases. In others, no malignant or inflammatory conditions have yet been identified. The range of SSAT-1 activity in individuals living in Bangladesh was significantly higher than in the Canadian cohort. Bangladesh volunteers live in an area of known to have high natural contamination with arsenic, a recognized carcinogen and they are exposed to high levels of air pollution. Conclusions: By this assay, high SSAT-1 activity has been confirmed in patients harbouring malignancy; however, pre-malignant and inflammatory conditions may result in a positive test. Follow-up of individuals with elevated SSAT-1 activity may reveal unrecognized malignancies, pre-malignant neoplasms, liver disease, inflammatory conditions and possibly false-positivity in individuals exposed to carcinogens such as arsenic. In further work, SSAT-1 up-regulation is being correlated with 5 other putative polyamine metabolite markers for accurate diagnosis of lung cancer.

scholarly journals The PAX3-FOXO1 oncogene alters exosome miRNA content and leads to paracrine effects mediated by exosomal miR-486

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Farah Ghamloush ◽  
Sandra E. Ghayad ◽  
Ghina Rammal ◽  
Assil Fahs ◽  
Abeer J. Ayoub ◽  
...  
Keyword(s):  
Cell Metabolism ◽  
Recipient Cell ◽  
Paracrine Signaling ◽  
Serum Samples ◽  
Paracrine Effects ◽  
Cellular Invasion ◽  
Downstream Effector ◽  
Mirna Content

Abstract Rhabdomyosarcoma (RMS) is the most common soft tissue sarcoma in children. The alveolar subtype (ARMS) is clinically more aggressive, and characterized by an oncogenic fusion protein PAX3-FOXO1 that drives oncogenic cellular properties. Exosomes are small, secreted vesicles that affect paracrine signaling. We show that PAX3-FOXO1 transcript alters exosome content of C2C12 myoblasts, leading to pro-tumorigenic paracrine effects in recipient cells. Microarray analysis revealed alteration in miRNA content of exosomes, affecting cellular networks involved in cell metabolism, growth signaling, and cellular invasion. Overexpression and knockdown studies showed that miR-486-5p is an effector of PAX3-FOXO1, and mediates its paracrine effects in exosomes, including promoting recipient cell migration, invasion, and colony formation. Analysis of human RMS cells showed miR-486-5p is enriched in both cells and exosomes, and to a higher extent in ARMS subtypes. Analysis of human serum samples showed that miR-486-5p is enriched in exosomes of patients with RMS, and follow-up after chemotherapy showed decrease to control values. Our findings identify a novel role of both PAX3-FOXO1 and its downstream effector miR-486-5p in exosome-mediated oncogenic paracrine effects of RMS, and suggest its possible use as a biomarker.

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