Three Types of Striational Antibodies in Myasthenia Gravis

Myasthenia gravis (MG) is caused by antibodies that react mainly with the acetylcholine receptor on the postsynaptic site of the neuromuscular junction. A wide range of clinical presentations and associated features allow MG to be classified into subtypes based onautoantibodystatus. Striational antibodies, which react with epitopes on the muscle proteins titin, ryanodine receptor (RyR), and Kv1.4, are frequently found in MG patients with late-onset and thymoma. Antititin and anti-RyR antibodies are determined by enzyme-linked immunosorbent assay or immunoblot. More recently, a method for the detection of anti-Kv1.4 autoantibodies has become available, involving 12–15% of all MG patients. The presence of striational antibodies is associated with more severe disease in all MG subgroups. Anti-Kv1.4 antibody is a useful marker for the potential development of lethal autoimmune myocarditis and response to calcineurin inhibitors. Detection of striational antibodies provides more specific and useful clinical information in MG patients.

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Predicting COVID-19 Severity with a Specific Nucleocapsid Antibody plus Disease Risk Factor Score

mSphere ◽

10.1128/msphere.00203-21 ◽

2021 ◽

Vol 6 (2) ◽

Author(s):

Sanjana R. Sen ◽

Emily C. Sanders ◽

Kristin N. Gabriel ◽

Brian M. Miller ◽

Hariny M. Isoda ◽

...

Keyword(s):

Risk Factor ◽

Factor Score ◽

Disease Risk ◽

Severe Disease ◽

Enzyme Linked Immunosorbent Assay ◽

Disease Risk Factor ◽

Disease States ◽

Wide Range ◽

Risk Factor Score ◽

Prognostic Prediction

ABSTRACT Effective methods for predicting COVID-19 disease trajectories are urgently needed. Here, enzyme-linked immunosorbent assay (ELISA) and coronavirus antigen microarray (COVAM) analysis mapped antibody epitopes in the plasma of COVID-19 patients (n = 86) experiencing a wide range of disease states. The experiments identified antibodies to a 21-residue epitope from nucleocapsid (termed Ep9) associated with severe disease, including admission to the intensive care unit (ICU), requirement for ventilators, or death. Importantly, anti-Ep9 antibodies can be detected within 6 days post-symptom onset and sometimes within 1 day. Furthermore, anti-Ep9 antibodies correlate with various comorbidities and hallmarks of immune hyperactivity. We introduce a simple-to-calculate, disease risk factor score to quantitate each patient’s comorbidities and age. For patients with anti-Ep9 antibodies, scores above 3.0 predict more severe disease outcomes with a 13.42 likelihood ratio (96.7% specificity). The results lay the groundwork for a new type of COVID-19 prognostic to allow early identification and triage of high-risk patients. Such information could guide more effective therapeutic intervention. IMPORTANCE The COVID-19 pandemic has resulted in over two million deaths worldwide. Despite efforts to fight the virus, the disease continues to overwhelm hospitals with severely ill patients. Diagnosis of COVID-19 is readily accomplished through a multitude of reliable testing platforms; however, prognostic prediction remains elusive. To this end, we identified a short epitope from the SARS-CoV-2 nucleocapsid protein and also a disease risk factor score based upon comorbidities and age. The presence of antibodies specifically binding to this epitope plus a score cutoff can predict severe COVID-19 outcomes with 96.7% specificity.

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Thymoma in Myasthenia Gravis: From Diagnosis to Treatment

Autoimmune Diseases ◽

10.4061/2011/474512 ◽

2011 ◽

Vol 2011 ◽

pp. 1-5 ◽

Cited By ~ 23

Author(s):

Fredrik Romi

Keyword(s):

Neuromuscular Junction ◽

Myasthenia Gravis ◽

Acetylcholine Receptor ◽

Ryanodine Receptor ◽

Pharmacological Treatment ◽

Respiratory Symptoms ◽

Late Onset ◽

Severe Disease ◽

Symptom Profile

One half of cortical thymoma patients develop myasthenia gravis (MG), while 15% of MG patients have thymomas. MG is a neuromuscular junction disease caused in 85% of the cases by acetylcholine receptor (AChR) antibodies. Titin and ryanodine receptor (RyR) antibodies are found in 95% of thymoma MG and 50% of late-onset MG (MG onset ≥50 years), are associated with severe disease, and may predict thymoma MG outcome. Nonlimb symptom profile at MG onset with bulbar, ocular, neck, and respiratory symptoms should raise the suspicion about the presence of thymoma in MG. The presence of titin and RyR antibodies in an MG patient younger than 60 years strongly suggests a thymoma, while their absence at any age strongly excludes thymoma. Thymoma should be removed surgically. Prethymectomy plasmapheresis/iv-IgG should be considered before thymectomy. The pharmacological treatment does not differ from nonthymoma MG, except for tacrolimus which is an option in difficult thymoma and nonthymoma MG cases with RyR antibodies.

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A Severe Disease of Tomato in the Culiacan Area (Sinaloa, Mexico) Is Caused by a New Picorna-Like Viral Species

Plant Disease ◽

10.1094/pdis-91-8-0932 ◽

2007 ◽

Vol 91 (8) ◽

pp. 932-941 ◽

Cited By ~ 35

Author(s):

M. Turina ◽

M. D. Ricker ◽

R. Lenzi ◽

V. Masenga ◽

M. Ciuffo

Keyword(s):

Severe Disease ◽

Chenopodium Quinoa ◽

Wide Distribution ◽

Enzyme Linked Immunosorbent Assay ◽

Virus Species ◽

Serological Tests ◽

Rna Molecules ◽

Wide Range ◽

Length Analysis ◽

Solanaceous Plants

We were able to mechanically transmit a small isometric virus from field tomato samples showing severe necrotic symptoms, collected in the Culiacan area of Sinaloa state (Mexico). After gradient purification and three rounds of single-lesion passage on Chenopodium quinoa, the virus was back-inoculated to tomato plants and reproduced the original apical necrosis symptoms. The virus could be transmitted to a wide range of experimental hosts, including a number of solanaceous plants. Purified virus was used to produce specific polyclonal rabbit antibodies and serological tests such as enzyme-linked immunosorbent assay, Western blot analysis, and an immunochromatographic lateral flow assay. Such assays confirmed the wide distribution of this virus in symptomatic field plants in the area of the epidemic. Purified particles contained two genomic RNA molecules of ca. 7 kb (RNA1) and 5 kb (RNA2) estimated length. Analysis of clones from a cDNA library provided 6.5 and 3.0 kb of sequence for RNA1 and RNA2, respectively. Sequence analysis of the encoded replicase showed greatest similarity with members of the Sequiviridae family, and indicated that the virus we isolated is a new virus species, provisionally named Tomato apex necrosis virus.

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First Detection of Tobacco Mosaic Virus in Tobacco Fields in Northern Lebanon

Infectious Disorders - Drug Targets ◽

10.2174/1871526520666200928164057 ◽

2020 ◽

Vol 20 ◽

Author(s):

Rami Obeid ◽

Elias Wehbe ◽

Mohamad Rima ◽

Mohammad Kabara ◽

Romeo Al Bersaoui ◽

...

Keyword(s):

Tobacco Mosaic Virus ◽

Mosaic Virus ◽

Viral Genome ◽

Virus Genome ◽

Enzyme Linked Immunosorbent Assay ◽

Virus Family ◽

Crop Fields ◽

Wide Range ◽

Almost All ◽

Das Elisa

Background: Tobacco mosaic virus (TMV) is the most known virus in the plant mosaic virus family and is able to infect a wide range of crops, in particularly tobacco, causing a production loss. Objectives: Herein, and for the first time in Lebanon, we investigated the presence of TMV infection in crops by analyzing 88 samples of tobacco, tomato, cucumber and pepper collected from different regions in North Lebanon. Methods: Double-antibody sandwich enzyme-linked immunosorbent assay (DAS-ELISA), revealed a potential TMV infection of four tobacco samples out of 88 crops samples collected. However, no tomato, cucumber and pepper samples were infected. The TMV+ tobacco samples were then extensively analyzed by RT-PCR to detect viral RNA using different primers covering all the viral genome. Results and Discussion: PCR results confirmed those of DAS-ELISA showing TMV infection of four tobacco samples collected from three crop fields of North Lebanon. In only one of four TMV+ samples, we were able to amplify almost all the regions of viral genome, suggesting possible mutations in the virus genome or an infection with a new, not yet identified, TMV strain. Conclusion: Our study is the first in Lebanon revealing TMV infection in crop fields, and highlighting the danger that may affect the future of agriculture.

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Multiple Myeloma or Brucellosis: A Case Report

Infectious Disorders - Drug Targets ◽

10.2174/1871526519666190307123047 ◽

2020 ◽

Vol 20 (1) ◽

pp. 102-105 ◽

Cited By ~ 1

Author(s):

Hossein A. Rahdar ◽

Mansoor Kodori ◽

Mohamad R. Salehi ◽

Mahsa Doomanlou ◽

Morteza Karami-Zarandi ◽

...

Keyword(s):

Multiple Myeloma ◽

Brucella Melitensis ◽

Severe Disease ◽

Correct Diagnosis ◽

Clinical Manifestations ◽

Bone Marrow Aspiration ◽

Major Health Problem ◽

Brucella Infection ◽

Wide Range ◽

Parental Treatment

Background: Brucellosis, a major health problem in developing countries, is a multisystem infection with a broad spectrum of clinical manifestations. Hematological complications, ranging from an intravascular coagulopathy to mild homeostasis disorders (such as gammopathy), have been reported in brucella infection. These signs and symptoms may lead to misdiagnosis of brucellosis with other hematological diseases. Case: A 65-year-old male whose occupation was shepherding was referred to our hospital as a known case of multiple myeloma with continuous fever, muscle weakness, and night sweating after taking 2 courses of chemotherapy. The laboratory diagnosis of multiple myeloma had been based on the observation of a high percent of plasma cells in the bone marrow aspiration. At follow- up, the result of patient's fever workup, with 2 sets of blood cultures, was positive for Brucella melitensis. Isolated brucella was confirmed as B. melitensis by 16S rRNA sequencing. Brucellosis serologic test was performed by agglutination test and positive results were obtained. The patient was discharged with the cessation of fever and general improvement after the end of the parental treatment phase of brucella bacteremia. Conclusions: Brucella infection may cause a severe disease, mimicking a primary hematological disease, which could complicate the correct diagnosis. In brucellosis cases, due to the wide range of symptoms, in addition to cultivation and serological methods, molecular methods should also be used to prevent inappropriate diagnosis and additional costs.

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332 The diagnostic role of shunt series radiographs (SSR) in children presenting to the children’s emergency department (CED) with suspected ventriculoperitoneal (VP) shunt failure

Emergency Medicine Journal ◽

10.1136/emj-2020-rcemabstracts.56 ◽

2020 ◽

Vol 37 (12) ◽

pp. 852.3-853

Author(s):

Angharad Griffiths ◽

Ikechukwu Okafor ◽

Thomas Beattie

Keyword(s):

Clinical Outcome ◽

Sensitivity And Specificity ◽

Clinical Information ◽

Flow Diagram ◽

List Type ◽

Shunt Failure ◽

Vp Shunt ◽

Wide Range ◽

Diagnostic Role

Aims/Objectives/BackgroundVP shunts are used to drain CSF from the cranial vault because of a wide range of pathologies and, like any piece of hardware, can fail. Traditionally investigations include SSR and CT. This project examines the role of SSR in evaluating children with suspected VP shunt failure.Primary outcome: Sensitivity and specificity of SSR in children presenting to the CED with concern for shunt failure.Methods/DesignConducted in a single centre, tertiary CED of the national Irish Neurosurgical(NS) referral centre (ED attendance:>50,000 patients/year). 100 sequential SSR requested by the CED were reviewed. Clinical information was extracted from electronic requests. Shunt failure was defined by the need for NS intervention(Revision).Abstract 332 Figure 1Abstract 332 Figure 2Results/ConclusionsSensitivity and specificity is presented in figure 1 (two by two table).100 radiographs performed in 84 children.22% shunts revised (see flow diagram).7 SSR’s were abnormal.85% (n=6) shunts revised. [5 following abnormal CT].Of the normal SSR’s; 16 had abnormal CT and revised.85/100 received CT.64 of 85 CT’s (75%) were normal.□6 of the 64 had focal shunt concern.SSR’s shouldn’t be used in isolation. NPV&PPV, Sensitivity&Specificity is low.SSR’s are beneficial where there’s concern over focal shunt problems (injury/pain/swelling) or following abnormal CT.VP shunt failure is not well investigated with SSR alone.SSR’s could be omitted where there is no focal shunt concern/after normal CT (without impacting clinical outcome) reducing radiation exposure and reduce impact on CED’s.59 SSR’s could have been avoided without adverse clinical outcome.

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Informing the public health response to COVID-19: a systematic review of risk factors for disease, severity, and mortality

BMC Infectious Diseases ◽

10.1186/s12879-021-05992-1 ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

M. Flook ◽

C. Jackson ◽

E. Vasileiou ◽

C. R. Simpson ◽

M. D. Muckian ◽

...

Keyword(s):

Public Health ◽

Risk Factors ◽

Systematic Review ◽

At Risk ◽

Risk Factor ◽

Disease Severity ◽

Severe Disease ◽

Public Health Response ◽

Wide Range ◽

Multivariable Analyses

Abstract Background Severe Acute Respiratory Syndrome coronavirus-2 (SARS-CoV-2) has challenged public health agencies globally. In order to effectively target government responses, it is critical to identify the individuals most at risk of coronavirus disease-19 (COVID-19), developing severe clinical signs, and mortality. We undertook a systematic review of the literature to present the current status of scientific knowledge in these areas and describe the need for unified global approaches, moving forwards, as well as lessons learnt for future pandemics. Methods Medline, Embase and Global Health were searched to the end of April 2020, as well as the Web of Science. Search terms were specific to the SARS-CoV-2 virus and COVID-19. Comparative studies of risk factors from any setting, population group and in any language were included. Titles, abstracts and full texts were screened by two reviewers and extracted in duplicate into a standardised form. Data were extracted on risk factors for COVID-19 disease, severe disease, or death and were narratively and descriptively synthesised. Results One thousand two hundred and thirty-eight papers were identified post-deduplication. Thirty-three met our inclusion criteria, of which 26 were from China. Six assessed the risk of contracting the disease, 20 the risk of having severe disease and ten the risk of dying. Age, gender and co-morbidities were commonly assessed as risk factors. The weight of evidence showed increasing age to be associated with severe disease and mortality, and general comorbidities with mortality. Only seven studies presented multivariable analyses and power was generally limited. A wide range of definitions were used for disease severity. Conclusions The volume of literature generated in the short time since the appearance of SARS-CoV-2 has been considerable. Many studies have sought to document the risk factors for COVID-19 disease, disease severity and mortality; age was the only risk factor based on robust studies and with a consistent body of evidence. Mechanistic studies are required to understand why age is such an important risk factor. At the start of pandemics, large, standardised, studies that use multivariable analyses are urgently needed so that the populations most at risk can be rapidly protected. Registration This review was registered on PROSPERO as CRD42020177714.

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Long non-coding RNA OIP5-AS1 aggravates acute lung injury by promoting inflammation and cell apoptosis via regulating the miR-26a-5p/TLR4 axis

BMC Pulmonary Medicine ◽

10.1186/s12890-021-01589-1 ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Qingsong Sun ◽

Man Luo ◽

Zhiwei Gao ◽

Xiang Han ◽

Weiqin Wu ◽

...

Keyword(s):

Acute Lung Injury ◽

Lung Injury ◽

Inflammatory Response ◽

Cell Apoptosis ◽

Quantitative Polymerase Chain Reaction ◽

Luciferase Reporter ◽

Enzyme Linked Immunosorbent Assay ◽

Interacting Protein ◽

Wide Range

Abstract Background Acute lung injury (ALI) is a pulmonary disorder that leads to acute respiration failure and thereby results in a high mortality worldwide. Increasing studies have indicated that toll-like receptor 4 (TLR4) is a promoter in ALI, and we aimed to explore the underlying upstream mechanism of TLR4 in ALI. Methods We used lipopolysaccharide (LPS) to induce an acute inflammatory response in vitro model and a murine mouse model. A wide range of experiments including reverse transcription quantitative polymerase chain reaction, western blot, enzyme linked immunosorbent assay, flow cytometry, hematoxylin–eosin staining, RNA immunoprecipitation, luciferase activity and caspase-3 activity detection assays were conducted to figure out the expression status, specific role and potential upstream mechanism of TLR4 in ALI. Result TLR4 expression was upregulated in ALI mice and LPS-treated primary bronchial/tracheal epithelial cells. Moreover, miR-26a-5p was confirmed to target TLR4 according to results of luciferase reporter assay. In addition, miR-26a-5p overexpression decreased the contents of proinflammatory factors and inhibited cell apoptosis, while upregulation of TLR4 reversed these effects of miR-26a-5p mimics, implying that miR-26a-5p alleviated ALI by regulating TLR4. Afterwards, OPA interacting protein 5 antisense RNA 1 (OIP5-AS1) was identified to bind with miR-26a-5p. Functionally, OIP5-AS1 upregulation promoted the inflammation and miR-26a-5p overexpression counteracted the influence of OIP5-AS1 upregulation on cell inflammatory response and apoptosis. Conclusion OIP5-AS1 promotes ALI by regulating the miR-26a-5p/TLR4 axis in ALI mice and LPS-treated cells, which indicates a promising insight into diagnostics and therapeutics in ALI.

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Differences in Clinical and Dietary Characteristics, Serum Adipokine Levels, and Metabolomic Profiles between Early- and Late-Onset Gout

Metabolites ◽

10.3390/metabo11060399 ◽

2021 ◽

Vol 11 (6) ◽

pp. 399

Author(s):

Young Sun Suh ◽

Hae Sook Noh ◽

Hyun-Jin Kim ◽

Yun-Hong Cheon ◽

Mingyo Kim ◽

...

Keyword(s):

Early Onset ◽

Late Onset ◽

Clinical Information ◽

Plasminogen Activator Inhibitor ◽

Ultra Performance Liquid Chromatography ◽

Plasminogen Activator Inhibitor 1 ◽

Baseline Serum ◽

Onset Group ◽

Early Onset Group ◽

Pai 1

This study aimed to identify differences in clinical and dietary characteristics, serum adipokine levels, and metabolomic profiles between early- and late-onset gout. Eighty-three men with gout were divided into an early-onset group (n = 38, aged < 40 years) and a late-onset group (n = 45, aged ≥ 40 years). Dietary and clinical information was obtained at baseline. Serum adipokines, including adiponectin, resistin, leptin, and plasminogen activator inhibitor-1 (PAI-1), were quantified by a Luminex multiplex immunoassay. Metabolite expression levels in plasma were measured in 22 representative samples using metabolomics analysis based on ultra-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry. Average body mass index, rate of consumption of sugar-sweetened beverages, and serum uric acid levels were significantly higher in the early-onset group (p < 0.05), as was the PAI-I concentration (105.01 ± 42.45 ng/mL vs. 83.76 ± 31.16 ng/mL, p = 0.013). Changes in levels of metabolites mostly involved those related to lipid metabolism. In the early-onset group, acylcarnitine analog and propylparaben levels were downregulated and negatively correlated with the PAI-1 concentration whereas LPC (22:6) and LPC (18:0) levels were upregulated and positively correlated with the PAI-1 concentration. Dietary and clinical features, serum adipokine concentrations, and metabolites differed according to whether the gout is early-onset or late-onset. The mechanisms of gout may differ between these groups and require different treatment approaches.

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Post-thymectomy myasthenia gravis: a case report and systematic review of literature

BMJ Case Reports ◽

10.1136/bcr-2021-246005 ◽

2021 ◽

Vol 14 (12) ◽

pp. e246005

Author(s):

Louise Gurowich ◽

Gabriel Yiin ◽

Adam Maxwell ◽

Alexandra Rice

Keyword(s):

Systematic Review ◽

Case Report ◽

Myasthenia Gravis ◽

Early Onset ◽

Late Onset ◽

High Morbidity ◽

Review Of Literature ◽

Prompt Treatment ◽

Autoimmune Condition ◽

Anti Acetylcholine

Myasthenia gravis (MG) is an autoimmune condition affecting the neuromuscular junction characterised by weakness and fatiguability, carrying a high morbidity if treatment is delayed. A clear association with thymoma has led to management with thymectomy as a common practice, but MG presenting post-thymectomy has rarely been reported. We present a case of an 82- year-old woman developing fatigue, ptosis and dysarthria 3 months after thymectomy. After a clinical diagnosis of MG was made, she responded well to prompt treatment with prednisolone and pyridostigmine. Her anti-acetylcholine receptor antibody (anti-AChR) subsequently came back positive. Our systematic review reveals that post-thymectomy MG can be categorised as early-onset or late-onset form with differing aetiology, and demonstrated correlation between preoperative anti-AChR titres and post-thymectomy MG. The postulated mechanisms for post-thymectomy MG centre around long-lasting peripheral autoantibodies. Clinicians should actively look for MG symptoms in thymoma patients and measure anti-AChR preoperatively to aid prognostication.

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