{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,1]],"date-time":"2026-11-01T11:15:19Z","timestamp":1793531719755,"version":"4.5.0"},"reference-count":46,"publisher":"American Chemical Society (ACS)","issue":"8","license":[{"start":{"date-parts":[[2019,10,7]],"date-time":"2019-10-07T00:00:00Z","timestamp":1570406400000},"content-version":"vor","delay-in-days":73,"URL":"https:\/\/pubs.acs.org\/page\/policy\/authorchoice_ccby_termsofuse.html"}],"funder":[{"DOI":"10.13039\/100011263","name":"FP7 Nanosciences, Nanotechnologies, Materials and new Production Technologies","doi-asserted-by":"publisher","award":["309820"],"award-info":[{"award-number":["309820"]}],"id":[{"id":"10.13039\/100011263","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100011272","name":"FP7 Health","doi-asserted-by":"publisher","award":["602699"],"award-info":[{"award-number":["602699"]}],"id":[{"id":"10.13039\/100011272","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100011272","name":"FP7 Health","doi-asserted-by":"publisher","award":["602923"],"award-info":[{"award-number":["602923"]}],"id":[{"id":"10.13039\/100011272","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003549","name":"Orsz\u00e1gos Tudom\u00e1nyos Kutat\u00e1si Alapprogramok","doi-asserted-by":"publisher","award":["K-113164"],"award-info":[{"award-number":["K-113164"]}],"id":[{"id":"10.13039\/501100003549","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/na","name":"Applied Materials and Nanotechnology Center of Excellence, Miskolc University","doi-asserted-by":"publisher","award":["NA"],"award-info":[{"award-number":["NA"]}],"id":[{"id":"10.13039\/na","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/na","name":"Barenholz Fund","doi-asserted-by":"publisher","award":["NA"],"award-info":[{"award-number":["NA"]}],"id":[{"id":"10.13039\/na","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/na","name":"Norwegian Council on Cardiovascular Disease","doi-asserted-by":"publisher","award":["NA"],"award-info":[{"award-number":["NA"]}],"id":[{"id":"10.13039\/na","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/na","name":"Simon Fougner Hartmanns Familiefond","doi-asserted-by":"publisher","award":["NA"],"award-info":[{"award-number":["NA"]}],"id":[{"id":"10.13039\/na","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2019,8,27]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Polyethylene glycol (PEG)-coated nanopharmaceuticals can cause mild to severe hypersensitivity reactions (HSRs), which can occasionally be life threatening or even lethal. The phenomenon represents an unsolved immune barrier to the use of these drugs, yet its mechanism is poorly understood. This study showed that a single i.v. injection in pigs of a low dose of PEGylated liposomes (Doxebo) induced a massive rise of anti-PEG IgM in blood, peaking at days 7\u20139 and declining over 6 weeks. Bolus injections of PEG-liposomes during seroconversion resulted in anaphylactoid shock (pseudo-anaphylaxis) within 2\u20133 min, although similar treatments of na\u0131\u0308ve animals led to only mild hemodynamic disturbance. Parallel measurement of pulmonary arterial pressure (PAP) and sC5b-9 in blood, taken as measures of HSR and complement activation, respectively, showed a concordant rise of the two variables within 3 min and a decline within 15 min, suggesting a causal relationship between complement activation and pulmonary hypertension. We also observed a rapid decline of anti-PEG IgM in the blood within minutes, increased binding of PEGylated liposomes to IgM+ B cells in the spleen of immunized animals compared to control, and increased C3 conversion by PEGylated liposomes in the serum of immunized pigs. These observations taken together suggest rapid binding of anti-PEG IgM to PEGylated liposomes, leading to complement activation via the classical pathway, entailing anaphylactoid shock and accelerated blood clearance of liposome\u2013IgM complexes. These data suggest that complement activation plays a causal role in severe HSRs to PEGylated nanomedicines and that pigs can be used as a hazard identification model to assess the risk of HSRs in preclinical safety studies.<\/jats:p>","DOI":"10.1021\/acsnano.9b03942","type":"journal-article","created":{"date-parts":[[2019,7,26]],"date-time":"2019-07-26T15:38:45Z","timestamp":1564155525000},"page":"9315-9324","source":"Crossref","is-referenced-by-count":216,"title":["Pseudo-anaphylaxis\nto Polyethylene Glycol (PEG)-Coated\nLiposomes: Roles of Anti-PEG IgM and Complement Activation in a Porcine\nModel of Human Infusion Reactions"],"prefix":"10.1021","volume":"13","author":[{"given":"Gergely Tibor","family":"Kozma","sequence":"first","affiliation":[{"name":"Semmelweis University , , ,","place":["Budapest, Hungary, 1089"]},{"name":"SeroScience Ltd. , Budapest 1125, Hungary, and , ,","place":["Cambridge, Massachusetts, United States, 02138"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tama\u0301s","family":"Me\u0301sza\u0301ros","sequence":"additional","affiliation":[{"name":"Semmelweis University , , ,","place":["Budapest, Hungary, 1089"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ildiko\u0301","family":"Vashegyi","sequence":"additional","affiliation":[{"name":"SeroScience Ltd. , Budapest 1125, Hungary, and , ,","place":["Cambridge, Massachusetts, United States, 02138"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tama\u0301s","family":"Fu\u0308lo\u0308p","sequence":"additional","affiliation":[{"name":"Semmelweis University , , ,","place":["Budapest, Hungary, 1089"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erik","family":"O\u0308rfi","sequence":"additional","affiliation":[{"name":"Semmelweis University , , ,","place":["Budapest, Hungary, 1089"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"La\u0301szlo\u0301","family":"De\u0301zsi","sequence":"additional","affiliation":[{"name":"Semmelweis University , , ,","place":["Budapest, Hungary, 1089"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"La\u0301szlo\u0301","family":"Rosivall","sequence":"additional","affiliation":[{"name":"Semmelweis University , , ,","place":["Budapest, Hungary, 1089"]},{"name":"SeroScience Ltd. , Budapest 1125, Hungary, and , ,","place":["Cambridge, Massachusetts, United States, 02138"]},{"name":"Semmelweis University , , ,","place":["Budapest, Hungary, 1089"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yaelle","family":"Bavli","sequence":"additional","affiliation":[{"name":"Hebrew University-Hadassah Medical School , , ,","place":["Jerusalem, Israel, 9112102"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rudolf","family":"Urbanics","sequence":"additional","affiliation":[{"name":"Semmelweis University , , ,","place":["Budapest, Hungary, 1089"]},{"name":"SeroScience Ltd. , Budapest 1125, Hungary, and , ,","place":["Cambridge, Massachusetts, United States, 02138"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tom Eirik","family":"Mollnes","sequence":"additional","affiliation":[{"name":"Oslo University Hospital , , , ,","place":["Rikshospitalet, Oslo, Norway, 0372"]},{"name":"University of Troms\u00f8 , , ,","place":["Troms\u00f8, Norway, 9019"]},{"name":"Norwegian University of Science and Technology , , ,","place":["Trondheim, Norway, 7012"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yechezkel","family":"Barenholz","sequence":"additional","affiliation":[{"name":"Hebrew University-Hadassah Medical School , , ,","place":["Jerusalem, Israel, 9112102"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1738-797X","authenticated-orcid":true,"given":"Ja\u0301nos","family":"Szebeni","sequence":"additional","affiliation":[{"name":"Semmelweis University , , ,","place":["Budapest, Hungary, 1089"]},{"name":"SeroScience Ltd. , Budapest 1125, Hungary, and , ,","place":["Cambridge, Massachusetts, United States, 02138"]},{"name":"Miskolc University , , ,","place":["Miskolc, Hungary, 3515"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"316","published-online":{"date-parts":[[2019,7,26]]},"reference":[{"key":"2026090116051808800_cit1","doi-asserted-by":"publisher","first-page":"1315","DOI":"10.1111\/j.1572-0241.2003.07457.x","article-title":"The Incidence\nand Management of Infusion\nReactions to Infliximab: a Large Center Experience","volume":"98","author":"Cheifetz","year":"2003","journal-title":"Am. J. Gastroenterol."},{"key":"2026090116051808800_cit2","doi-asserted-by":"publisher","first-page":"857","DOI":"10.1016\/j.gtc.2006.09.006","article-title":"Infusion Reactions\nand Their Management","volume":"35","author":"Mayer","year":"2006","journal-title":"Gastroenterol\nClin North Am."},{"key":"2026090116051808800_cit3","doi-asserted-by":"publisher","first-page":"601","DOI":"10.1634\/theoncologist.12-5-601","article-title":"Management\nand Preparedness for Infusion and Hypersensitivity Reactions","volume":"12","author":"Lenz","year":"2007","journal-title":"Oncologist"},{"key":"2026090116051808800_cit4","doi-asserted-by":"publisher","first-page":"E10","DOI":"10.1188\/10.CJON.E10-E21","article-title":"Infusion\nReactions: Diagnosis, Assessment, and Management","volume":"14","author":"Vogel","year":"2010","journal-title":"Clin J. Oncol Nurs"},{"key":"2026090116051808800_cit5","doi-asserted-by":"publisher","first-page":"96","DOI":"10.1007\/s40629-014-0009-1","article-title":"Guideline for Acute Therapy and Management of Anaphylaxis","volume":"23","author":"Ring","year":"2014","journal-title":"Allergo J. Int."},{"key":"2026090116051808800_cit6","doi-asserted-by":"crossref","first-page":"271","DOI":"10.1684\/ejd.2017.2986","article-title":"Immediate\nHypersensitivity Reaction to PEGylated Liposomal Doxorubicin: Management\nand Outcome in Four Patients","volume":"27","author":"Ingen-Housz-Oro","year":"2017","journal-title":"Eur. J. Dermatol"},{"key":"2026090116051808800_cit7","doi-asserted-by":"publisher","first-page":"1100","DOI":"10.1038\/s41565-018-0273-1","article-title":"Roadmap and Strategy for Overcoming\nInfusion Reactions\nto Nanomedicines","volume":"13","author":"Szebeni","year":"2018","journal-title":"Nat. Nanotechnol."},{"key":"2026090116051808800_cit8","unstructured":"Doxil Prescribing\nInformation. https:\/\/www.accessdata.fda.gov\/drugsatfda_docs\/label\/2007\/050718s029lbl.pdf. Accessed July 17, 2019."},{"key":"2026090116051808800_cit9","doi-asserted-by":"publisher","first-page":"474","DOI":"10.1177\/1078155214542493","article-title":"Delayed Hypersensitivity\nReaction Related to the Use of Pegfilgrastim","volume":"21","author":"Dadla","year":"2015","journal-title":"J. Oncol. Pharm. Pract."},{"key":"2026090116051808800_cit10","first-page":"372","article-title":"Methoxy Polyethylene Glycol-Epoetin Beta (Mircera)\nin the Treatment of a Patient with Chronic Kidney Disease Presenting\nLate-Onset Hypersensitivity to Other Epoetins","volume":"30","author":"Davila Fajardo","year":"2010","journal-title":"Nefrologia"},{"key":"2026090116051808800_cit11","unstructured":"Jivi, A.\n           Antihemophilic Factor (Recombinant),\nPrescribing Information. https:\/\/www.fda.gov\/media\/94470\/download (accessed July 17, 2019)."},{"key":"2026090116051808800_cit12","unstructured":"Palynziq\n(pegvaliase-pqpz), Prescribing Information.https:\/\/www.palynziq.com\/prescribinginformation.pdf (accessed July 17, 2019)."},{"key":"2026090116051808800_cit13","doi-asserted-by":"publisher","first-page":"1421","DOI":"10.1080\/14740338.2016.1218467","article-title":"Peginesatide for the Treatment of\nAnemia Due To Chronic Kidney Disease - An Unfulfilled Promise","volume":"15","author":"Hermanson","year":"2016","journal-title":"Expert Opin. Drug Saf."},{"key":"2026090116051808800_cit14","doi-asserted-by":"publisher","first-page":"191","DOI":"10.1186\/s13075-017-1396-8","article-title":"Frequency,\nDistribution\nand Immunologic Nature of Infusion Reactions in Subjects Receiving\nPegloticase For Chronic Refractory Gout","volume":"19","author":"Calabrese","year":"2017","journal-title":"Arthritis\nRes. Ther."},{"key":"2026090116051808800_cit15","doi-asserted-by":"publisher","first-page":"2481","DOI":"10.1093\/eurheartj\/ehs232","article-title":"A Phase 2, Randomized, Partially\nBlinded, Active-Controlled Study Assessing The Efficacy and Safety\nof Variable Anticoagulation Reversal Using the REG1 System in Patients\nwith Acute Coronary Syndromes: Results of the RADAR Trial","volume":"34","author":"Povsic","year":"2013","journal-title":"Eur. Heart J."},{"key":"2026090116051808800_cit16","doi-asserted-by":"publisher","first-page":"1050","DOI":"10.1152\/ajpheart.00622.2005","article-title":"Complement Activation-Related\nCardiac\nAnaphylaxis in Pigs: Role of C5a Anaphylatoxin and Adenosine in Liposome-Induced\nAbnormalities in ECG and Heart Function","volume":"290","author":"Szebeni","year":"2006","journal-title":"Am.\nJ. Physiol Heart Circ Physiol"},{"key":"2026090116051808800_cit17","doi-asserted-by":"publisher","first-page":"1706","DOI":"10.1016\/j.addr.2012.07.005","article-title":"Porcine Model of Complement-Mediated\nInfusion Reactions\nto Drug Carrier Nanosystems and Other Medicines","volume":"64","author":"Szebeni","year":"2012","journal-title":"Adv. Drug Delivery Rev."},{"key":"2026090116051808800_cit18","doi-asserted-by":"publisher","first-page":"219","DOI":"10.1515\/ejnm-2015-0011","article-title":"Lessons Learned from the Porcine\nCARPA Model: Constant\nand Variable Responses to Different Nanomedicines and Administration\nProtocols","volume":"7","author":"Urbanics","year":"2015","journal-title":"Eur. J. Nanomed."},{"key":"2026090116051808800_cit19","doi-asserted-by":"publisher","first-page":"63","DOI":"10.29016\/180427.1","article-title":"Porcine Model of\nComplement Activation-Related Pseudoallergy to Nano-Pharmaceuticals:\nPros and Cons of Translation to a Preclinical Safety Test","volume":"1","author":"Szebeni","year":"2018","journal-title":"Prec Nanomed"},{"key":"2026090116051808800_cit20","doi-asserted-by":"publisher","first-page":"382","DOI":"10.1016\/j.jconrel.2012.02.029","article-title":"Prevention of Infusion Reactions\nto PEGylated Liposomal Doxorubicin via Tachyphylaxis\nInduction by Placebo Vesicles: a Porcine Model","volume":"160","author":"Szebeni","year":"2012","journal-title":"J. Controlled Release"},{"key":"2026090116051808800_cit21","doi-asserted-by":"publisher","first-page":"106","DOI":"10.1016\/j.tox.2005.07.023","article-title":"Complement\nActivation-Related Pseudoallergy: a New Class of Drug-Induced Acute\nImmune Toxicity","volume":"216","author":"Szebeni","year":"2005","journal-title":"Toxicology"},{"key":"2026090116051808800_cit22","doi-asserted-by":"publisher","first-page":"163","DOI":"10.1016\/j.molimm.2014.06.038","article-title":"Complement\nActivation-Related Pseudoallergy: a Stress Reaction in Blood Triggered\nby Nanomedicines and Biologicals","volume":"61","author":"Szebeni","year":"2014","journal-title":"Mol. Immunol."},{"key":"2026090116051808800_cit23","doi-asserted-by":"publisher","first-page":"1034","DOI":"10.1016\/j.drudis.2017.11.006","article-title":"Nanomedicine\nSafety in Preclinical and Clinical Development: Focus on Idiosyncratic\nInjection\/Infusion Reactions","volume":"23","author":"Moghimi","year":"2018","journal-title":"Drug Discovery\nToday"},{"key":"2026090116051808800_cit24","doi-asserted-by":"publisher","first-page":"589","DOI":"10.1038\/nnano.2017.47","article-title":"Bypassing Adverse Injection Reactions\nto Nanoparticles Through Shape Modification and Attachment to Erythrocytes","volume":"12","author":"Wibroe","year":"2017","journal-title":"Nat. Nanotechnol."},{"key":"2026090116051808800_cit25","doi-asserted-by":"publisher","first-page":"487","DOI":"10.1016\/j.drudis.2018.01.025","article-title":"Mechanism\nof Nanoparticle-Induced Hypersensitivity in Pigs: Complement or Not\nComplement?","volume":"23","author":"Szebeni","year":"2018","journal-title":"Drug Discovery Today"},{"key":"2026090116051808800_cit26","doi-asserted-by":"publisher","first-page":"6345","DOI":"10.2147\/IJN.S161369","article-title":"Involvement\nof Complement Activation in the Pulmonary Vasoactivity of Polystyrene\nNanoparticles in Pigs: Unique Surface Properties Underlying Alternative\nPathway Activation and Instant Opsonization","volume":"13","author":"Meszaros","year":"2018","journal-title":"Int. J. Nanomed."},{"key":"2026090116051808800_cit27","doi-asserted-by":"publisher","first-page":"467","DOI":"10.3109\/08982100009031112","article-title":"The Role of Complement Activation\nin Hypersensitivity to PEGylated Liposomal Doxorubicin (Doxil\u00ae)","volume":"10","author":"Szebeni","year":"2000","journal-title":"J. Liposome Res."},{"key":"2026090116051808800_cit28","doi-asserted-by":"publisher","first-page":"1430","DOI":"10.1093\/annonc\/mdg374","article-title":"Complement Activation\nFollowing First\nExposure to PEGylated Liposomal Doxorubicin (Doxil): Possible Role\nin Hypersensitivity Reactions","volume":"14","author":"Chanan-Khan","year":"2003","journal-title":"Ann. Oncol"},{"key":"2026090116051808800_cit29","doi-asserted-by":"publisher","first-page":"1563","DOI":"10.2147\/IJN.S187139","article-title":"Acute Physiological\nChanges Caused by Complement Activators and Amphotericin B-Containing\nLiposomes in Mice","volume":"14","author":"Orfi","year":"2019","journal-title":"Int. J. Nanomed."},{"key":"2026090116051808800_cit30","doi-asserted-by":"crossref","first-page":"1071","DOI":"10.1016\/S0022-3565(24)35391-1","article-title":"Accelerated Blood\nClearance and Altered Biodistribution of Repeated Injections of Sterically\nStabilized Liposomes","volume":"292","author":"Dams","year":"2000","journal-title":"J. Pharmacol Exp Ther"},{"key":"2026090116051808800_cit31","doi-asserted-by":"publisher","first-page":"305","DOI":"10.1016\/j.jconrel.2005.04.003","article-title":"Accelerated Blood Clearance\nof PEGylated Liposomes\nFollowing Preceding Liposome Injection: Effects of Lipid Dose and\nPEG Surface-Density and Chain Length of the First-Dose Liposomes","volume":"105","author":"Ishida","year":"2005","journal-title":"J. Controlled Release"},{"key":"2026090116051808800_cit32","doi-asserted-by":"publisher","first-page":"218","DOI":"10.1016\/j.ijpharm.2010.03.022","article-title":"T Cell-Independent B Cell Response\nIs Responsible for ABC Phenomenon\nInduced by Repeated Injection of PEGylated Liposomes","volume":"392","author":"Koide","year":"2010","journal-title":"Int. J. Pharm."},{"key":"2026090116051808800_cit33","doi-asserted-by":"publisher","first-page":"1151","DOI":"10.1016\/j.imbio.2015.06.005","article-title":"Anti-PEG IgM\nand Complement System\nAre Required for the Association of Second Doses of PEGylated Liposomes\nwith Splenic Marginal Zone B Cells","volume":"220","author":"Shimizu","year":"2015","journal-title":"Immunobiology"},{"key":"2026090116051808800_cit34","doi-asserted-by":"publisher","first-page":"417","DOI":"10.1248\/bpb.b14-00653","article-title":"Relationship\nbetween the Concentration of Anti-Polyethylene Glycol (PEG) Immunoglobulin\nM (IgM) and the Intensity of the Accelerated Blood Clearance (ABC)\nPhenomenon against PEGylated Liposomes in Mice","volume":"38","author":"Hashimoto","year":"2015","journal-title":"Biol. Pharm. Bull."},{"key":"2026090116051808800_cit35","first-page":"771","article-title":"Accelerated Blood\nClearance Phenomenon and Complement Activation-Related Pseudoallergy:\nTwo Sides of the Same Coin","volume-title":"Immune Effects\nof Biopharmaceuticals and Nanomedicines","author":"Abu Lila","year":"2018"},{"key":"2026090116051808800_cit36","doi-asserted-by":"publisher","first-page":"2","DOI":"10.1016\/j.jconrel.2014.08.009","article-title":"Features of\nComplement Activation-Related Pseudoallergy to Liposomes with Different\nSurface Charge and PEGylation: Comparison of the Porcine and Rat Responses","volume":"195","author":"Dezsi","year":"2014","journal-title":"J. Controlled Release"},{"key":"2026090116051808800_cit37","doi-asserted-by":"publisher","first-page":"1842","DOI":"10.1248\/bpb.b13-00562","article-title":"Ex Vivo\/In Vitro Anti-Polyethylene\nGlycol (PEG) Immunoglobulin M Production from Murine Splenic B Cells\nStimulated by PEGylated Liposome","volume":"36","author":"Abu Lila","year":"2013","journal-title":"Biol. Pharm.\nBull."},{"key":"2026090116051808800_cit38","doi-asserted-by":"publisher","first-page":"223","DOI":"10.1007\/s11095-018-2505-3","article-title":"A Cell Assay for Detecting Anti-PEG Immune Response\nagainst PEG-Modified Therapeutics","volume":"35","author":"Shimizu","year":"2018","journal-title":"Pharm. Res."},{"key":"2026090116051808800_cit39","doi-asserted-by":"publisher","first-page":"4877","DOI":"10.7150\/thno.22420","article-title":"Injection\nof Nanoparticles into Cloven-Hoof Animals: Asking for Trouble?","volume":"7","author":"Skotland","year":"2017","journal-title":"Theranostics"},{"key":"2026090116051808800_cit40","doi-asserted-by":"publisher","first-page":"973","DOI":"10.2217\/nnm-2018-0064","article-title":"Translational Gaps in Animal Models of Human Infusion\nReactions to Nanomedicines","volume":"13","author":"Moghimi","year":"2018","journal-title":"Nanomedicine (London,\nU. K.)"},{"key":"2026090116051808800_cit41","doi-asserted-by":"publisher","first-page":"370","DOI":"10.1124\/jpet.119.258012","article-title":"The Interplay\nBetween Blood Proteins, Complement, and Macrophages on Nanomedicine\nPerformance and Responses","author":"Moghimi","year":"2019","journal-title":"J. Pharmacol. Exp.\nTher."},{"key":"2026090116051808800_cit42","doi-asserted-by":"publisher","first-page":"1610","DOI":"10.1016\/j.jaci.2015.10.034","article-title":"Pre-Existing\nAnti-Polyethylene Glycol Antibody Linked to First-Exposure Allergic\nReactions to Pegnivacogin, a PEGylated RNA Aptamer","volume":"137","author":"Ganson","year":"2016","journal-title":"J. Allergy Clin. Immunol."},{"key":"2026090116051808800_cit43","doi-asserted-by":"publisher","first-page":"1712","DOI":"10.1016\/j.jaci.2016.04.058","article-title":"Pre-Existing Anti-Polyethylene Glycol\nAntibodies Are Associated with Severe Immediate Allergic Reactions\nto Pegnivacogin, a PEGylated Aptamer","volume":"138","author":"Povsic","year":"2016","journal-title":"J. Allergy\nClin. Immunol."},{"key":"2026090116051808800_cit44","doi-asserted-by":"publisher","first-page":"R63","DOI":"10.1186\/ar4500","article-title":"Induced and Pre-Existing Anti-Polyethylene\nGlycol Antibody\nin a Trial of Every 3-Week Dosing of Pegloticase for Refractory Gout,\nIncluding in Organ Transplant Recipients","volume":"16","author":"Hershfield","year":"2014","journal-title":"Arthritis\nRes. Ther"},{"key":"2026090116051808800_cit45","unstructured":"Kasperovic, P.\n          \n          Dosages\nand Methods for Delivering Lipid Formulated Nucleic Acid Molecules. U.S. patent application 20160122759, 2016."},{"key":"2026090116051808800_cit46","first-page":"1356","article-title":"Extensive Complement Activation in\nHereditary Porcine Membranoproliferative Glomerulonephritis Type II\n(Porcine Dense Deposit Disease)","volume":"143","author":"Jansen","year":"1993","journal-title":"Am. J. Pathol."}],"container-title":["ACS Nano"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pubs.acs.org\/doi\/pdf\/10.1021\/acsnano.9b03942","content-type":"application\/pdf","content-version":"vor","intended-application":"unspecified"},{"URL":"https:\/\/pubs.acs.org\/ancac3\/article-pdf\/13\/8\/9315\/67516632\/acsnano.9b03942.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/pubs.acs.org\/ancac3\/article-pdf\/13\/8\/9315\/67516632\/acsnano.9b03942.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T20:05:27Z","timestamp":1788293127000},"score":1,"resource":{"primary":{"URL":"https:\/\/pubs.acs.org\/ancac3\/article\/13\/8\/9315\/808511\/Pseudo-anaphylaxis-to-Polyethylene-Glycol-PEG"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,7,26]]},"references-count":46,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2019,7,26]]},"published-print":{"date-parts":[[2019,8,27]]}},"URL":"https:\/\/doi.org\/10.1021\/acsnano.9b03942","relation":{},"ISSN":["1936-0851","1936-086X"],"issn-type":[{"value":"1936-0851","type":"print"},{"value":"1936-086X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,7,26]]}}}