{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,24]],"date-time":"2026-08-24T19:52:19Z","timestamp":1787601139430,"version":"build-2736575974"},"reference-count":54,"publisher":"The Company of Biologists","issue":"9","license":[{"start":{"date-parts":[[2021,2,11]],"date-time":"2021-02-11T00:00:00Z","timestamp":1613001600000},"content-version":"vor","delay-in-days":163,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100001665","name":"Agence Nationale de la Recherche","doi-asserted-by":"publisher","award":["ANR-12-BSV3-0003"],"award-info":[{"award-number":["ANR-12-BSV3-0003"]}],"id":[{"id":"10.13039\/501100001665","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2020,9,1]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n               <jats:p>Bacterial pathogens have evolved to secrete strong anti-inflammatory proteins that target the immune system. It was long speculated whether these virulence factors could serve as therapeutics in diseases in which abnormal immune activation plays a role. We adopted the secreted chemotaxis inhibitory protein of Staphylococcus aureus (CHIPS) as a model virulence factor-based therapeutic agent for diseases in which C5AR1 stimulation plays an important role. We show that the administration of CHIPS in human C5AR1 knock-in mice successfully dampens C5a-mediated neutrophil migration during immune complex-initiated inflammation. Subsequent CHIPS toxicology studies in animal models were promising. However, during a small phase I trial, healthy human volunteers showed adverse effects directly after CHIPS administration. Subjects showed clinical signs of anaphylaxis with mild leukocytopenia and increased C-reactive protein concentrations, which are possibly related to the presence of relatively high circulating anti-CHIPS antibodies and suggest an inflammatory response. Even though our data in mice show CHIPS as a potential anti-inflammatory agent, safety issues in human subjects temper the use of CHIPS in its current form as a therapeutic candidate. The use of staphylococcal proteins, or other bacterial proteins, as therapeutics or immune-modulators in humans is severely hampered by pre-existing circulating antibodies.<\/jats:p>","DOI":"10.1242\/dmm.045534","type":"journal-article","created":{"date-parts":[[2020,5,29]],"date-time":"2020-05-29T20:04:33Z","timestamp":1590782673000},"source":"Crossref","is-referenced-by-count":4,"title":["Pre-existing antibody-mediated adverse effects prevent the clinical development of a bacterial anti-inflammatory protein"],"prefix":"10.1242","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3067-1940","authenticated-orcid":false,"given":"Angelino T.","family":"Tromp","sequence":"first","affiliation":[{"name":"University Medical Center Utrecht 1 Department of Medical Microbiology , , 3584CX Utrecht , The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4440-8257","authenticated-orcid":false,"given":"Yuxi","family":"Zhao","sequence":"additional","affiliation":[{"name":"University Medical Center Utrecht 1 Department of Medical Microbiology , , 3584CX Utrecht , The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7759-9897","authenticated-orcid":false,"given":"Ilse","family":"Jongerius","sequence":"additional","affiliation":[{"name":"University Medical Center Utrecht 1 Department of Medical Microbiology , , 3584CX Utrecht , The Netherlands"},{"name":"Sanquin Research 2 , Department of Immunopathology , 1006AD Amsterdam , The Netherlands"},{"name":"Amsterdam UMC, University of Amsterdam 3 Landsteiner Laboratory , , 1105AZ Amsterdam , The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erik C. 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