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In most cases, immune complexes are readily cleared from circulation; however, based on physiochemical properties, insoluble complexes form, activate complement, and deposit in tissues. Using published information and personal experience, a set of repeat-dose monkey toxicity studies with manifestations suggestive of ICD was reviewed to summarize the spectrum of clinical and pathology findings. The most common live-phase observation linked to ICD was an acute postdosing reaction following multiple dose administrations characterized by generalized collapse and attributed to acute complement activation. Less common live-phase observations were related to syndromes such as a consumptive coagulopathy or a protein losing nephropathy. The most common histologic change attributed to ICD was multi-organ vascular\/perivascular inflammation followed by glomerulonephritis. The presentation concluded with a description of the challenges in assessing the relevance of immunogenicity-related reaction in monkey to human clinical use.<\/jats:p>","DOI":"10.1177\/0192623318797070","type":"journal-article","created":{"date-parts":[[2018,8,29]],"date-time":"2018-08-29T23:05:28Z","timestamp":1535583928000},"page":"1013-1019","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":17,"title":["Immunogenicity and Immune Complex Disease in Preclinical Safety Studies"],"prefix":"10.1177","volume":"46","author":[{"given":"John L.","family":"Vahle","sequence":"first","affiliation":[{"name":"Lilly Research Laboratories, Indianapolis, Indiana, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2018,8,29]]},"reference":[{"key":"bibr1-0192623318797070","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V99.7.2599"},{"key":"bibr2-0192623318797070","doi-asserted-by":"publisher","DOI":"10.1016\/j.it.2007.07.011"},{"key":"bibr3-0192623318797070","doi-asserted-by":"publisher","DOI":"10.1177\/0192623314522559"},{"key":"bibr4-0192623318797070","doi-asserted-by":"publisher","DOI":"10.1177\/0192623317723539"},{"key":"bibr5-0192623318797070","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2016.00021"},{"key":"bibr6-0192623318797070","doi-asserted-by":"publisher","DOI":"10.1016\/j.yrtph.2017.06.004"},{"key":"bibr7-0192623318797070","doi-asserted-by":"publisher","DOI":"10.1128\/CDLI.1.4.365-372.1994"},{"key":"bibr8-0192623318797070","doi-asserted-by":"publisher","DOI":"10.1177\/0192623313510987"},{"key":"bibr9-0192623318797070","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V98.12.3241"},{"key":"bibr10-0192623318797070","doi-asserted-by":"publisher","DOI":"10.1016\/j.cotox.2017.03.005"},{"key":"bibr11-0192623318797070","doi-asserted-by":"publisher","DOI":"10.1016\/j.jim.2014.11.007"},{"key":"bibr12-0192623318797070","doi-asserted-by":"publisher","DOI":"10.1016\/j.yrtph.2009.03.012"},{"key":"bibr13-0192623318797070","doi-asserted-by":"publisher","DOI":"10.1124\/jpet.104.079277"},{"key":"bibr14-0192623318797070","doi-asserted-by":"publisher","DOI":"10.1177\/0192623314526475"},{"key":"bibr15-0192623318797070","doi-asserted-by":"publisher","DOI":"10.1016\/j.cellimm.2015.03.002"}],"container-title":["Toxicologic Pathology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1177\/0192623318797070","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/full-xml\/10.1177\/0192623318797070","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1177\/0192623318797070","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,1]],"date-time":"2026-05-01T16:39:38Z","timestamp":1777653578000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.sagepub.com\/doi\/10.1177\/0192623318797070"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,8,29]]},"references-count":15,"journal-issue":{"issue":"8","published-print":{"date-parts":[[2018,12]]}},"alternative-id":["10.1177\/0192623318797070"],"URL":"https:\/\/doi.org\/10.1177\/0192623318797070","relation":{},"ISSN":["0192-6233","1533-1601"],"issn-type":[{"value":"0192-6233","type":"print"},{"value":"1533-1601","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,8,29]]}}}