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Immune complex disease affects a small number of study monkeys, often correlates with antidrug antibody (ADA) titers, and occurs at a dose that favors immune complex formation or impedes clearance. While preclinical glomerulonephritis often fails to correlate with evidence of glomerular or vascular injury in human clinical trials and is not considered predictive, additional animal investigative immunohistochemical work may be performed to substantiate evidence for immune complex pathogenesis. While ADA is most commonly encountered as a predisposing factor with biotherapeutic agents, complement activation may occur without circulating complexes, and other mechanisms of non-ADA immune-mediated glomerulonephritis have been observed including nonendogenous immune aggregates and immunoregulatory pharmacology. Although glomerulonephritis associated with oligonucleotide therapies has been noted occasionally in preclinical studies and more rarely with human patients, pathophysiologic mechanisms involved appear to be different between species and preclinical cases are not considered predictive for humans. ADA is not involved in oligonucleotide-associated cases, and complement fixation plays a more important role in monkeys. Recent screening of ASOs for proinflammatory activity appears to have decreased glomerulonephritis incidence preclinically.<\/jats:p>","DOI":"10.1177\/0192623318789399","type":"journal-article","created":{"date-parts":[[2018,8,8]],"date-time":"2018-08-08T21:15:40Z","timestamp":1533762940000},"page":"904-917","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":29,"title":["Drug-induced Glomerulonephritis: The Spectre of Biotherapeutic and Antisense Oligonucleotide Immune Activation in the Kidney"],"prefix":"10.1177","volume":"46","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4608-5543","authenticated-orcid":false,"given":"Kendall S.","family":"Frazier","sequence":"first","affiliation":[{"name":"GlaxoSmithKline, King of Prussia, Pennsylvania, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Leslie A.","family":"Obert","sequence":"additional","affiliation":[{"name":"GlaxoSmithKline, King of Prussia, Pennsylvania, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"179","published-online":{"date-parts":[[2018,8,8]]},"reference":[{"key":"bibr1-0192623318789399","doi-asserted-by":"publisher","DOI":"10.1007\/s11523-015-0368-7"},{"key":"bibr2-0192623318789399","doi-asserted-by":"publisher","DOI":"10.1016\/0192-0561(93)90006-K"},{"key":"bibr3-0192623318789399","first-page":"465","volume":"35","author":"Alexander N. 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