{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,1,23]],"date-time":"2026-01-23T08:54:41Z","timestamp":1769158481669,"version":"3.49.0"},"posted":{"date-parts":[[2024,5,10]]},"group-title":"Pathology","reference-count":18,"publisher":"openRxiv","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2024,5,10]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>\n                  Alpha-1 antitrypsin (AAT) deficiency is the most common genetic cause of emphysema. Chymotrypsin-like Elastase 1 (CELA1) is a serine protease neutralized by AAT and is important in emphysema progression.\n                  <jats:italic>Cela1<\/jats:italic>\n                  -deficiency is protective in a murine models of AAT-deficient emphysema. KF4 anti-CELA1 antibody prevented emphysema in PPE and cigarette smoke models in wild type mice. We evaluated potential toxicities of KF4 and its ability to prevent emphysema in AAT deficiency. We found Cela1 protein expression in mouse lung, pancreas, small intestine, and spleen. In toxicity studies, mice treated with KF4 25 mg\/kg weekly for four weeks showed an elevation in blood urea nitrogen and slower weight gain compared to lower doses or equivalent dose IgG. In histologic grading of tissue injury of the lung, kidney, liver, and heart, there was some evidence of liver injury with KF4 25 mg\/kg, but in all tissues, injury was less than in control mice subjected to cecal ligation and puncture. In efficacy studies, KF4 doses as low as 0.5 mg\/kg reduced the lung elastase activity of\n                  <jats:italic>\n                    AAT\n                    <jats:sup>-\/-<\/jats:sup>\n                  <\/jats:italic>\n                  mice treated with 0.2 units of PPE. In this injury model,\n                  <jats:italic>\n                    AAT\n                    <jats:sup>-\/-<\/jats:sup>\n                  <\/jats:italic>\n                  mice treated with KF4 1 mg\/kg weekly, human purified AAT 60 mg\/kg weekly, and combined KF4 and AAT treatment had less emphysema than mice treated with IgG 1 mg\/kg weekly. However, the efficacy of KF4, AAT, or KF4 &amp; AAT was similar. While KF4 might be an alternative to AAT replacement, combined KF4 and AAT replacement does not confer additional benefit.\n                <\/jats:p>","DOI":"10.1101\/2024.05.07.592994","type":"posted-content","created":{"date-parts":[[2024,5,10]],"date-time":"2024-05-10T22:05:08Z","timestamp":1715378708000},"source":"Crossref","is-referenced-by-count":2,"title":["KF4 anti-CELA1 Antibody and Purified \u03b11-Antitrypsin Have Similar but Not Additive Efficacy in Preventing Emphysema in Murine \u03b11-Antitrypsin Deficiency"],"prefix":"10.64898","author":[{"given":"Andrew J.","family":"Devine","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Noah J.","family":"Smith","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rashika","family":"Joshi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Brandon","family":"Brooks-Patton","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jenna","family":"Dunham","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ansley N.","family":"Varisco","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Emily M.","family":"Goodman","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qiang","family":"Fan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Basilia","family":"Zingarelli","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Brian M.","family":"Varisco","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"54368","reference":[{"key":"2024051423301250000_2024.05.07.592994v1.1","doi-asserted-by":"publisher","DOI":"10.1165\/rcmb.2016-0331OC"},{"key":"2024051423301250000_2024.05.07.592994v1.2","first-page":"Cd007851","article-title":"Intravenous alpha-1 antitrypsin augmentation therapy for treating patients with alpha-1 antitrypsin deficiency and lung disease","volume":"9","year":"2016","journal-title":"The Cochrane database of systematic reviews"},{"key":"2024051423301250000_2024.05.07.592994v1.3","doi-asserted-by":"crossref","unstructured":"Adam Wanner MD . Towards New Therapeutic Solutions for Alpha-1 Antitrypsin Deficiency: Role of the Alpha-1 Foundation. 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R: A Language and Environment for Statistical Computing. Vienna, Austria: R Foundation for Statistical Computing; 2019."},{"key":"2024051423301250000_2024.05.07.592994v1.13","unstructured":"Kassambara A. rstatix: Pipe-Friendly Framework for Basic Statistical Tests. 2020. https:\/\/CRAN.R-project.org\/package=rstatix. Accessed August 20, 2020."},{"key":"2024051423301250000_2024.05.07.592994v1.14","unstructured":"Kassambara A. ggpubr: Publication Ready Plots - Articles - STHDA [Internet]. 2020. http:\/\/www.sthda.com\/english\/articles\/24-ggpubr-publication-ready-plots\/. Accessed May 15, 2020."},{"key":"2024051423301250000_2024.05.07.592994v1.15","unstructured":"Gamer M , Lemon J , Fellows I. irr: Various Coefficients of Interrater Reliability and Agreement. 2019. https:\/\/CRAN.R-project.org\/package=irr."},{"key":"2024051423301250000_2024.05.07.592994v1.16","unstructured":"The Human Protein Atlas [Internet]. https:\/\/www.proteinatlas.org\/. 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