scholarly journals History of safe exposure and bioinformatic assessment of phosphomannose-isomerase (PMI) for allergenic risk

2021 ◽  
Vol 30 (2) ◽  
pp. 201-206
Author(s):  
Rod A. Herman ◽  
Zhenglin Hou ◽  
Henry Mirsky ◽  
Mark E. Nelson ◽  
Carey A. Mathesius ◽  
...  

AbstractNewly expressed proteins in genetically engineered crops are evaluated for potential cross reactivity to known allergens as part of their safety assessment. This assessment uses a weight-of-evidence approach. Two key components of this allergenicity assessment include any history of safe human exposure to the protein and/or the source organism from which it was originally derived, and bioinformatic analysis identifying amino acid sequence relatedness to known allergens. Phosphomannose-isomerase (PMI) has been expressed in commercialized genetically engineered (GE) crops as a selectable marker since 2010 with no known reports of allergy, which supports a history of safe exposure, and GE events expressing the PMI protein have been approved globally based on expert safety analysis. Bioinformatic analyses identified an eight-amino-acid contiguous match between PMI and a frog parvalbumin allergen (CAC83047.1). While short amino acid matches have been shown to be a poor predictor of allergen cross reactivity, most regulatory bodies require such matches be assessed in support of the allergenicity risk assessment. Here, this match is shown to be of negligible risk of conferring cross reactivity with known allergens.

Author(s):  
Rod A. Herman ◽  
Jason M. Roper

There continues to be an erroneous belief that allergens (especially food allergens) are more resistant to gastrointestinal digestion than non-allergens. Government regulations based on this erroneous belief may result in technology developers altering the amino acid sequences of digestively stable native proteins to create digestively unstable modified versions for expression in genetically engineered crops. However, an investigation where a known stable allergen was modified to make it more digestible eliminated the protein’s ability to tolerize against allergy in a mouse model, which is consistent with the dual allergen exposure hypothesis. Thus, the false belief that digestive stability increases the allergenic risk of novel food proteins (e.g., such as expressed in genetically engineered crops) could, in some cases, lead to introduction of digestively unstable modified protein versions with greater sensitization risk. However, it is noteworthy that developers have historically been very effective at preventing allergens from being introduced into crops based on the other components of the weight-of-evidence assessment of allergenic risk such that no newly expressed protein in any commercialized genetically engineered crop has ever been documented to cause allergy in anyone.


2020 ◽  
Vol 22 (9) ◽  
pp. 657-662 ◽  
Author(s):  
Mustafa Celik ◽  
Alper Şen ◽  
İsmail Koyuncu ◽  
Ataman Gönel

Aim and Objective:: To determine the mechanisms present in the etiopathogenesis of nasal polyposis. It is not clear whether amino acids contribute in a causal way to the development of the disease. Therefore, the aim of this study was to determine the plasma-free amino acid profile in patients with nasal polyposis and to compare the results with a healthy control group. Materials and Methods:: This was a prospective controlled study that took place in the Otolaryngology Department at the Harran University Faculty of Medicine between April 2017 and April 2018. Plasmafree amino acid profile levels were studied in serum samples taken from a patient group and a healthy control group. Patients who were diagnosed with bilateral diffuse nasal polyposis and were scheduled for surgical interventions were included in this study. Individuals whose age, gender, and body mass index values were compatible with that of the patient group and who did not have any health problems were included in the control group. All the participants whose levels of plasma-free amino acid were thought to be affected by one or more of the following factors were excluded from the study: smoking and alcohol use, allergic rhinitis presence, the presence of acute or chronic sinusitis, a history of endoscopic sinus surgery, unilateral nasal masses, a history of chronic drug use, systemic or topical steroid use in the last three months for any reason, and liver, kidney, hematological, cardiovascular, metabolic, neurological, or psychiatric disorders or malignancies. Results: In patients with nasal polyposis, 3-methyl histidine (3-MHIS: nasal polyposis group (ng) = 3.22 (1.92 – 6.07); control group (cg) = 1.21 (0.77 – 1.68); p = 0.001); arginine (arg: ng = 98.95 (70.81 – 117.75); cg = 75.10 (54.49 – 79.88); p = 0.005); asparagine (asn: ng = 79.84 (57.50 – 101.44); cg = 60.66 (46.39 – 74.62); p = 0.021); citrulline (cit: ng = 51.83 (43.81 – 59.78); cg = 38.33 (27.81 – 53.73); p = 0.038); cystine (cys: ng = 4.29 (2.43 – 6.66); cg = 2.41 (1.51 – 4.16); p = 0.019); glutamic acid (glu: ng = 234.86 (128.75 – 286.66); cg = 152.37 (122.51 – 188.34); p = 0.045); histidine (his: ng = 94.19 (79.34 – 113.99); cg = 74.80 (62.76 – 98.91); p = 0.018); lysine (lys: ng = 297.22 (206.55 – 371.25); cg = 179.50 (151.58 – 238.02); p = 0.001); ornithine (ng = 160.62 (128.36 – 189.32); cg = 115.91 (97.03 – 159.91); p = 0.019); serine (ser: ng = 195.15 (151.58 – 253.07); cg = 83.07 (67.44 – 92.44); p = 0.001); taurine (tau: ng = 74.69 (47.00 – 112.13); cg = 53.14 (33.57 – 67.31); p = 0.006); tryptophan (trp: ng = 52.31 (33.81 – 80.11); cg = 34.44 (25.94 – 43.07); p = 0.005), homocitrulline (ng = 1.75 (1.27 – 2.59); cg = 0.00 (0.00 – 0.53); p = 0.001); norvaline (ng = 6.90 (5.61 – 9.18); cg = 4.93 (3.74 – 7.13); p = 0.021); argininosuccinic acid (ng = 14.33 (10.06 – 25.65); cg = 12.22 (5.77 – 16.87) p = 0.046); and plasma concentrations were significantly higher than in the healthy control group (p <0.05). However, the gamma-aminobutyric acid (gaba: ng = 0.16 (0.10 – 0.24); cg = 0.21 (0.19 – 0.29); p = 0.010) plasma concentration was significantly lower in the nasal polyposis group than in the healthy control group. Conclusion: In this study, plasma levels of 15 free amino acids were significantly higher in the nasal polyposis group than in the healthy control group. A plasma level of 1 free amino acid was found to be significantly lower in the nasal polyposis group compared to the healthy control group. Therefore, it is important to determine the possibility of using the information obtained to prevent the recurrence of the condition and to develop effective treatment strategies. This study may be a milestone for studies of this subject. However, this study needs to be confirmed by further studies conducted in a larger series.


2013 ◽  
Vol 18 (6) ◽  
pp. 312-324 ◽  
Author(s):  
Gemma Masip ◽  
Maite Sabalza ◽  
Eduard Pérez-Massot ◽  
Raviraj Banakar ◽  
David Cebrian ◽  
...  

2004 ◽  
Vol 385 (1) ◽  
pp. 319-327 ◽  
Author(s):  
Regina WICHE ◽  
Michaela GUBESCH ◽  
Herbert KÖNIG ◽  
Kay FÖTISCH ◽  
Andreas HOFFMANN ◽  
...  

Birch (Betula verrucosa) pollen-associated food allergy is a well-characterized syndrome, which is due to the cross-reactivity of IgE antibodies to homologous allergens in various foods. One crossreacting area on the major birch pollen allergen Bet v 1 and its homologue in cherry (Prunus avium) Pru av 1 has already been identified. This is the so-called ‘P-loop’ region, which encompasses amino acid residues around position 45 and is found on the two virtually identical tertiary protein structures. We tried to determine an additional IgE cross-reacting patch on Pru av 1 and Bet v 1. The putative IgE-binding region on Pru av 1 was localized with a mAb (monoclonal antibody) that was generated against Bet v 1, and cross-reacts with several Bet v 1 homologues in food and inhibits the binding of patients' IgE to Pru av 1. mAb reactivity pattern was analysed and amino acid positions 28 and 108 of Pru av 1 were selected and mutated by site-directed mutagenesis. The Pru av 1 mutants were produced as recombinant proteins and characterized for their folding, mAb- and IgE-binding capacity and allergenic potency with a cellular assay using the humanized rat basophilic leukaemia cell line RBL-25/30. Amino acid position 28 is involved in a second major IgE-binding region on Pru av 1 and probably on Bet v 1. The identification of this second major IgE-binding region is an essential prerequisite to understand the phenomenon of cross-reactivity and its clinical consequences, and to produce hypoallergenic proteins for an improved immunotherapy of type I allergy.


Acoustics ◽  
2021 ◽  
Vol 3 (1) ◽  
pp. 118-136
Author(s):  
John L. Drever ◽  
Aysegul Yildirim ◽  
Mattia Cobianchi

In a leading article by Sir Percival Philips in the UK popular newspaper, the Daily Mail, July 16, 1928, came the following headlines: “Millions Lost by Noise – Cities’ Worst Plague – Menace to Nerves and Health – What is Being Done to Stop it”. The article was supported by research from Prof Henry J. Spooner, who had been researching and campaigning on the ill-effects of noise and its economic impact. The article sparked subsequent discussion and follow-up articles in the Daily Mail and its international partners. In an era of rapid technological change, that was on the cusp of implementing sound pressure measurements, the Daily Mail, in collaboration with the Columbia Graphophone Company Ltd, experimented with sound recording technology and commentary in the field to help communicate perceived loudness and identify the sources of “unnecessary noise”. This resulted in the making of series of environmental sound recordings from five locations across central London during September 1928, the findings of which were documented and discussed in the Daily Mail at the time, and two recordings commercially released by Columbia on shellac gramophone disc. This was probably the first concerted anti-noise campaign of this type and scale, requiring huge technological efforts. The regulatory bodies and politicians of the time reviewed and improved the policies around urban noise shortly after the presentation of the recordings, which were also broadcast from the BBC both nationally and internationally, and many members of the public congratulated and thanked the Daily Mail for such an initiative. Despite its unpreceded scale and impact, and the recent scholarly attention on the history of anti-noise campaigning, this paper charts and contextualises the Daily Mail’s London Street Noise campaign for the first time. As well as historical research, this data has also been used to start a longitudinal comparative study still underway, returning to make field recordings on the site on the 80th and 90th anniversaries and during the COVID-19 lockdown, and shared on the website londonstreetnoises.co.uk.


2002 ◽  
Vol 21 (sup3) ◽  
pp. 199S-204S ◽  
Author(s):  
Robert Sévenier ◽  
Ingrid M. van der Meer ◽  
Raoul Bino ◽  
Andries J. Koops

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Patamalai Boonserm ◽  
Songchan Puthong ◽  
Thanaporn Wichai ◽  
Sajee Noitang ◽  
Pongsak Khunrae ◽  
...  

AbstractIt is important to understand the amino acid residues that govern the properties of the binding between antibodies and ligands. We studied the binding of two anti-norfloxacins, anti-nor 132 and anti-nor 155, and the fluoroquinolones norfloxacin, enrofloxacin, ciprofloxacin, and ofloxacin. Binding cross-reactivities tested by an indirect competitive enzyme-linked immunosorbent assay indicated that anti-nor 132 (22–100%) had a broader range of cross-reactivity than anti-nor 155 (62–100%). These cross-reactivities correlated with variations in the numbers of interacting amino acid residues and their positions. Molecular docking was employed to investigate the molecular interactions between the fluoroquinolones and the monoclonal antibodies. Homology models of the heavy chain and light chain variable regions of each mAb 3D structure were docked with the fluoroquinolones targeting the crucial part of the complementarity-determining regions. The fluoroquinolone binding site of anti-nor 155 was a region of the HCDR3 and LCDR3 loops in which hydrogen bonds were formed with TYR (H:35), ASN (H:101), LYS (H:106), ASN (L:92), and ASN (L:93). These regions were further away in anti-nor 132 and could not contact the fluoroquinolones. Another binding region consisting of HIS (L:38) and ASP (H:100) was found for norfloxacin, enrofloxacin, and ciprofloxacin, whereas only ASP (H:100) was found for ofloxacin.


Author(s):  
Jessica L Johnson ◽  
Ashley Hawthorne ◽  
Michael Bounds ◽  
David J Weldon

Abstract Purpose Propofol is an intravenous sedative used in many patient populations and care settings. Although generally considered safe and effective, the drug has historically been avoided in patients with reported allergies to egg, soy, and/or peanut on the basis of the manufacturer’s prescribing information. Concerns exist for potential adverse events, increased medication costs, reduced efficacy, and risk of medication errors when using alternative agents. Here we present a critical examination of the literature concerning cross-reactivity of food allergies with propofol to provide evidence-based recommendations for the evaluation and management of potential allergic reactions. Summary Literature regarding the history of propofol allergy warnings and clinical trial data were assessed to provide an alternative perspective on avoidance of propofol in patients with food allergies. Suspected trigger molecules are discussed with evaluation of the antigenic potential of excipient ingredients used in the manufacture of multiple propofol formulations. Evidence-based recommendations are provided for pharmacist-led screening of adult patients with reported food allergies to support selection of propofol or alternative therapy. Conclusion There is a lack of definitive evidence that propofol must be routinely avoided in patients with reported allergies to egg, soy, and/or peanut products. Data from clinical trials suggest that propofol is safe for patients with nonanaphylactic food allergies. Patients who do experience allergic reactions following administration of propofol should undergo further testing to definitively identify the specific trigger and prevent future unnecessary avoidance of preferred medication regimens. Pharmacists can play an important role in interviewing patients with reported food allergies to better determine the risk vs benefit of propofol avoidance.


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