LitCovid-sample-sentences  

PMC:7361216 / 3086-9233 JSONTXT 24 Projects

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Id Subject Object Predicate Lexical cue
T18 0-15 Sentence denotes 1 INTRODUCTION
T19 16-166 Sentence denotes A demyelinating neuropathy targeting myelin‐associated glycoprotein (MAG) has an incidence of approximately one per 100,000 (Mygland & Monstad, 2001).
T20 167-403 Sentence denotes In this disease there is production of an IgM antibody resulting in a “monoclonal gammopathy” targeting a particular carbohydrate known as Cellular Differentiation antigen 57 (CD57) and also known as human natural killer cell‐1 (HNK‐1).
T21 404-566 Sentence denotes The HNK‐1 antigen is found on MAG, as well as on natural killer cells, neuroectodermal tissue, retina, brain, prostate and renal proximal tubules (Pernick, 2019).
T22 567-700 Sentence denotes CD57 belongs to a family of sialic acid‐binding Ig‐like lectins (siglecs) found on both peripheral and central nervous system myelin.
T23 701-950 Sentence denotes In this issue investigators (Aliu et al, 2020) showed that poly(phenyl disodium 3‐O‐sulfo‐β‐d‐glucopyranuronate)‐(1→3)‐β‐d‐galactopyranoside, known as PPSGG, removed anti‐MAG IgM autoantibodies from the blood in a mouse model of this IgM neuropathy.
T24 951-1106 Sentence denotes In a previous study these investigators developed antigen‐specific molecules with nanomolar inhibitory potency for anti‐MAG IgM (Herrendorff et al., 2017).
T25 1107-1250 Sentence denotes Here the investigators also show that PPSGG blocked the binding of an anti‐MAG IgM from patients to sciatic nerve myelin of non‐human primates.
T26 1251-1336 Sentence denotes They also tested some of the pharmacokinetic and pharmacodynamic properties of PPSGG.
T27 1337-1509 Sentence denotes In patients suffering from this IgM monoclonal gammopathy, non‐specific strategies are used to diminish IgM antibody including targeting of all CD20 B cells with Rituximab.
T28 1510-1661 Sentence denotes On occasion flares of disease occur with increased IgM levels of antibody targeting MAG have followed therapy with Rituximab (Broglio and Luria, 2005).
T29 1662-1771 Sentence denotes The strategy employed with PPSGG is specific to the antigen that triggers the pathogenic IgM in this disease.
T30 1772-1851 Sentence denotes One can refer to such treatment as “antigen‐specific” immunotherapy (Figure 1).
T31 1852-2259 Sentence denotes FIGURE 1 The strategy employed by Aliu et al, provide a basis for a passive immune therapy with a decoy carbohydrate preventing the virus from docking on its receptor, and also provide a foundation for a carbohydrate‐based active immunization when coupled to a suitable carrier Investigations in the mouse model revealed that practical doses of PPSGG were able to sufficiently reduce IgM that binds to MAG.
T32 2260-2386 Sentence denotes Doses between 1 and 10 µg were sufficient to remove between 23 and 93% of IgM anti‐MAG antibody from blood in the mouse model.
T33 2387-2536 Sentence denotes Reductions in antibody were sustained for as long as 96 hr, demonstrating the pharmacologic feasibility of this highly specific therapeutic approach.
T34 2537-2677 Sentence denotes In addition the investigators showed that after exposure to PPSGG, there was no activation of B cells, including human IgM anti‐MAG B cells.
T35 2678-2743 Sentence denotes In addition, no activation of CD11b dendritic cells was observed.
T36 2744-2862 Sentence denotes These experiments provide some assurance on the safety of this approach, if it is translated to human clinical trials.
T37 2863-2955 Sentence denotes Engaging IgM targeting MAG with PPSGG appeared safe and effective in the pre‐clinical study.
T38 2956-3240 Sentence denotes Writing about these exquisite approaches to targeting carbohydrates for a potential antigen‐specific therapy for an inflammatory neuropathy characterized by sensory impairment, disturbance in gait, tremor, and ataxia (a form of incoordination following sensory loss) makes one wonder:
T39 3241-3418 Sentence denotes Could such an approach, targeting critical carbohydrates in a disease, have broader applicability to other diseases where complex carbohydrates play a key pathophysiologic role?
T40 3419-3633 Sentence denotes In these days of the COVID‐19 pandemic, the experiments described on monoclonal IgM neuropathy raise the issue that a similar strategy might be deployed to target the carbohydrates in the spike protein of COVID‐19.
T41 3634-3704 Sentence denotes Spike proteins in coronviruses are known to be camouflaged by glycans:
T42 3705-3853 Sentence denotes Mass spectrometry studies revealed in a feline coronavirus that high mannose and complex N‐Glycans accounted for a quarter of the mass of the spike.
T43 3854-3977 Sentence denotes Moreover, the N‐glycans are critical for providing the propeller like conformation of these structures (Yang et al., 2020).
T44 3978-4099 Sentence denotes In the so‐called receptor‐binding domain of the spike protein there are 22 glycan‐binding sites (Shahajan, Supekar et al.
T45 4100-4106 Sentence denotes 2020).
T46 4107-4230 Sentence denotes High mannose, hybrid and complex‐type glycans across the N‐glycosylation sites have been identified with mass spectrometry.
T47 4231-4439 Sentence denotes One could imagine building a therapeutic which might contain the carbohydrates, or a suitable mimic, of the spike protein coupled to a carrier molecule, much in a similar fashion to how PPSGG was constructed.
T48 4440-4591 Sentence denotes Such a “decoy” carbohydrate could block the binding and subsequent internalization of COViD‐19 to its receptor, angiotensin converting enzyme‐2 (ACE2).
T49 4592-4693 Sentence denotes In addition, spike carbohydrate clusters coupled to a carrier might proof to be an effective vaccine.
T50 4694-4826 Sentence denotes Both the pneumococcal vaccine and the meningococcal vaccines target polysaccharides in pneumococcus and meningococcus, respectively.
T51 4827-4947 Sentence denotes They couple the appropriate polysaccharide to a suitable carrier to achieve potent carbohydrate‐specific immunogenicity.
T52 4948-5167 Sentence denotes In a different neuroinflammatory disease antibodies to cryptic mannose containing glycans were observed in the cerebrospinal fluid of individuals with multiple sclerosis, and in its animal model EAE (Wang et al., 2014).
T53 5168-5258 Sentence denotes There again is some precedent for an antigen‐specific therapy for an inflammatory disease.
T54 5259-5410 Sentence denotes Injection of these oligomannose glycans coupled to a protein carrier reduced the clinical severity of paralysis in this animal model (Wang, Bhat et al.
T55 5411-5417 Sentence denotes 2014).
T56 5418-5552 Sentence denotes The success in parlaying the oligomannose glycans in MS and in its EAE model, could be emulated in strategies for therapy of COVID‐19.
T57 5553-5618 Sentence denotes IgM monoclonal gammopathy targeting MAG is indeed a rare disease.
T58 5619-5721 Sentence denotes Lessons from rare diseases often inform us of bold approaches for the treatment of widespread disease.
T59 5722-5900 Sentence denotes The pioneering work of Aliu and colleagues described in this issue, might serve as a guidepost for designing effective therapeutics to the glycan components of the COVID19 virus.
T60 5901-6073 Sentence denotes Such endeavors may produce a sweet ending to a tragedy including both the harsh clinical realities of IgM MAG neuropathy and to the horrors of the deadly CoVID‐19 pandemic.
T61 6075-6096 Sentence denotes CONFLICTS OF INTEREST
T62 6097-6147 Sentence denotes The author has no conflict of interest to declare.