{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,4]],"date-time":"2026-09-04T15:27:17Z","timestamp":1788535637449,"version":"build-2803163510"},"reference-count":42,"publisher":"American Chemical Society (ACS)","issue":"9","license":[{"start":{"date-parts":[[2026,7,31]],"date-time":"2026-07-31T00:00:00Z","timestamp":1785456000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,9,4]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Biologics, lipid nanoparticles, and other therapeutic modalities can result in adverse events, often detected as lesions during preclinical pathology assessments. Characterization of these lesions provides valuable information during drug development to contextualize mechanisms of injury and assess species translatability. Here, we investigated the utility of a laser capture microdissection (LCM)-enriched mass spectrometry proteomics approach to analyze two well-characterized preclinical models of regional (glomerular) injury: Passive Heyman Nephritis in rats and bovine gamma globulin-induced glomerular injury in nonhuman primates (NHPs). Using LCM-enriched proteomics, glomeruli were isolated from formalin-fixed paraffin-embedded kidney tissue in the rat model, enabling identification of 4,661 proteins and quantification of 3,410. Proteinuria measurements were compared with digital pathology metrics of glomerular morphology and proteomics results, with all modalities yielding concordant evidence of glomerular injury and proteomics confirming the role of complement activation. The same LCM- enriched proteomics workflow was applied to an NHP model of induced glomerular damage, identifying 4,623 proteins, quantifying 3,000, and confirming qualitative concordance with established features of complement-mediated glomerular injury. Together, these findings illustrate the applicability of LCM-enriched proteomics for region-specific characterization of antibody-mediated tissue injury and support its use as a hypothesis-generating platform in translational toxicologic pathology.<\/jats:p>","DOI":"10.1021\/acs.jproteome.6c00389","type":"journal-article","created":{"date-parts":[[2026,8,4]],"date-time":"2026-08-04T14:03:02Z","timestamp":1785852182000},"page":"4859-4869","source":"Crossref","is-referenced-by-count":0,"title":["LCM-Enriched\nProteomic Characterization of Antibody-Mediated\nGlomerular Damage and Complement Activation in Pre-Clinical Models"],"prefix":"10.1021","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0009-0003-7103-1728","authenticated-orcid":true,"given":"Carlos A.","family":"Morales-Betanzos","sequence":"first","affiliation":[{"name":"Pfizer, Inc. , , , ,","place":["Andover, Massachusetts, United States, 01810"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joel D.","family":"Federspiel","sequence":"additional","affiliation":[{"name":"Pfizer, Inc. , , , ,","place":["Andover, Massachusetts, United States, 01810"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jameel","family":"Syed","sequence":"additional","affiliation":[{"name":"Pfizer, Inc. , , , ,","place":["Groton, Connecticut, United States, 06340"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Smitha","family":"Pillai","sequence":"additional","affiliation":[{"name":"Pfizer, Inc. , , , ,","place":["La Jolla, California, United States, 92121"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah","family":"Vargas","sequence":"additional","affiliation":[{"name":"Pfizer, Inc. , , , ,","place":["Groton, Connecticut, United States, 06340"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Timothy","family":"Coskran","sequence":"additional","affiliation":[{"name":"Pfizer, Inc. , , , ,","place":["Groton, Connecticut, United States, 06340"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8985-5643","authenticated-orcid":true,"given":"Mireia","family":"Fernandez Ocana","sequence":"additional","affiliation":[{"name":"Pfizer, Inc. , , , ,","place":["Andover, Massachusetts, United States, 01810"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"316","published-online":{"date-parts":[[2026,7,31]]},"reference":[{"key":"2026090409123323200_cit1","doi-asserted-by":"publisher","first-page":"599974","DOI":"10.3389\/fimmu.2020.599974","article-title":"Deposition of the Membrane Attack Complex in Healthy and Diseased\nHuman Kidneys","volume":"11","author":"Koopman","year":"2021","journal-title":"Front. 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Lett."},{"issue":"1","key":"2026090409123323200_cit4","doi-asserted-by":"publisher","first-page":"710","DOI":"10.1080\/14686996.2019.1627174","article-title":"PEGylated\nliposomes: immunological responses","volume":"20","author":"Mohamed","year":"2019","journal-title":"Sci. Technol.\nAdv. Mater."},{"issue":"2\u20133","key":"2026090409123323200_cit5","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":"2026090409123323200_cit6","doi-asserted-by":"crossref","first-page":"171","DOI":"10.1016\/B978-0-12-397188-3.00008-1","article-title":"Chapter 8 -\nMechanisms of Cell and Tissue Damage","volume-title":"Mims\u2019\nPathogenesis of Infectious Disease","author":"Nash","year":"2015","edition":"(Sixth)"},{"issue":"1","key":"2026090409123323200_cit7","doi-asserted-by":"publisher","first-page":"191","DOI":"10.1080\/1547691X.2019.1680776","article-title":"Formation and glomerular deposition\nof immune complexes in mice administered bovine serum albumin: Evaluation\nof dose, frequency, and biomarkers","volume":"16","author":"Boysen","year":"2019","journal-title":"J. Immunotoxicol."},{"issue":"21","key":"2026090409123323200_cit8","doi-asserted-by":"publisher","first-page":"13263","DOI":"10.3390\/ijms232113263","article-title":"Immune Modulation\nby Myeloid-Derived Suppressor Cells in Diabetic Kidney Disease","volume":"23","author":"Hsieh","year":"2022","journal-title":"Int. J. Mol. Sci."},{"issue":"2","key":"2026090409123323200_cit9","doi-asserted-by":"publisher","first-page":"792","DOI":"10.1124\/pharmrev.120.000072","article-title":"Therapeutic Targeting of the Complement\nSystem: From Rare Diseases to Pandemics","volume":"73","author":"Garred","year":"2021","journal-title":"Pharmacol.\nRev."},{"issue":"1","key":"2026090409123323200_cit10","first-page":"138","article-title":"In vivo detection\nof deposition of\nradiolabeled lupus antikidney antibody and its inhibition by soluble\nantigen","volume":"42","author":"Lee","year":"2001","journal-title":"J. Nucl. 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Protoc."},{"issue":"7","key":"2026090409123323200_cit19","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0021800","article-title":"REVIGO summarizes\nand\nvisualizes long lists of gene ontology terms","volume":"6","author":"Supek","year":"2011","journal-title":"PLoS One"},{"issue":"4","key":"2026090409123323200_cit20","doi-asserted-by":"publisher","first-page":"485","DOI":"10.1007\/s00428-005-0134-9","article-title":"Upregulation of nestin, vimentin,\nand desmin in rat podocytes in response to injury","volume":"448","author":"Zou","year":"2006","journal-title":"Virchows Arch"},{"issue":"5","key":"2026090409123323200_cit21","doi-asserted-by":"publisher","first-page":"813","DOI":"10.1007\/s12192-018-0890-5","article-title":"Small heat shock\nprotein speciation: novel non-canonical 44 kDa HspB5-related protein\nspecies in rat and human tissues","volume":"23","author":"Benndorf","year":"2018","journal-title":"Cell Stress\nChaperones"},{"issue":"1","key":"2026090409123323200_cit22","doi-asserted-by":"publisher","first-page":"14888","DOI":"10.1038\/s41598-020-71629-z","article-title":"Glomerular clusterin expression is\nincreased in diabetic nephropathy and protects against oxidative stress-induced\napoptosis in podocytes","volume":"10","author":"He","year":"2020","journal-title":"Sci. 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Nephrol"},{"issue":"8","key":"2026090409123323200_cit33","doi-asserted-by":"publisher","first-page":"1988","DOI":"10.1074\/mcp.M800518-MCP200","article-title":"Equivalence of protein inventories\nobtained from formalin-fixed paraffin-embedded and frozen tissue in\nmultidimensional liquid chromatography-tandem mass spectrometry shotgun\nproteomic analysis","volume":"8","author":"Sprung","year":"2009","journal-title":"Mol. Cell. Proteomics"},{"issue":"2","key":"2026090409123323200_cit34","doi-asserted-by":"publisher","first-page":"973","DOI":"10.1021\/acs.jproteome.9b00686","article-title":"HYPERsol: High-Quality\nData from Archival FFPE Tissue for Clinical Proteomics","volume":"19","author":"Marchione","year":"2020","journal-title":"J. Proteome Res."},{"issue":"1","key":"2026090409123323200_cit35","doi-asserted-by":"publisher","first-page":"5","DOI":"10.1186\/s12014-025-09529-5","article-title":"The\neffect of storage time and temperature\non the proteomic analysis of FFPE tissue sections","volume":"22","author":"Koh","year":"2025","journal-title":"Clin. Proteomics"},{"key":"2026090409123323200_cit36","doi-asserted-by":"publisher","first-page":"26","DOI":"10.1186\/s12014-018-9202-4","article-title":"Residual tissue repositories\nas a resource for population-based cancer proteomic studies","volume":"15","author":"Piehowski","year":"2018","journal-title":"Clin. 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Rep."},{"issue":"3","key":"2026090409123323200_cit38","doi-asserted-by":"publisher","first-page":"838","DOI":"10.1016\/j.cell.2020.10.021","article-title":"Coordinated\nCellular Neighborhoods Orchestrate\nAntitumoral Immunity at the Colorectal Cancer Invasive Front","volume":"183","author":"Schurch","year":"2020","journal-title":"Cell"},{"issue":"1","key":"2026090409123323200_cit39","doi-asserted-by":"publisher","first-page":"20","DOI":"10.1038\/s44303-024-00025-3","article-title":"Mass spectrometry imaging for spatially resolved multi-omics molecular\nmapping","volume":"2","author":"Zhang","year":"2024","journal-title":"Npj Imaging"},{"issue":"14","key":"2026090409123323200_cit40","doi-asserted-by":"publisher","first-page":"7589","DOI":"10.1021\/acs.analchem.5c00157","article-title":"Advances in Tandem\nMass Spectrometry Imaging for Next-Generation\nSpatial Metabolomics","volume":"97","author":"Qian","year":"2025","journal-title":"Anal. Chem."},{"issue":"1","key":"2026090409123323200_cit41","doi-asserted-by":"publisher","first-page":"8","DOI":"10.1038\/s41467-019-13858-z","article-title":"Automated mass spectrometry imaging of over 2000 proteins from tissue\nsections at 100-mum spatial resolution","volume":"11","author":"Piehowski","year":"2020","journal-title":"Nat.\nCommun."},{"issue":"6","key":"2026090409123323200_cit42","doi-asserted-by":"publisher","first-page":"888","DOI":"10.1007\/s11307-018-1267-y","article-title":"Mass Spectrometry Imaging and Integration\nwith Other Imaging Modalities for Greater Molecular Understanding\nof Biological Tissues","volume":"20","author":"Porta Siegel","year":"2018","journal-title":"Mol. Imaging Biol."}],"container-title":["Journal of Proteome Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pubs.acs.org\/doi\/pdf\/10.1021\/acs.jproteome.6c00389","content-type":"application\/pdf","content-version":"vor","intended-application":"unspecified"},{"URL":"https:\/\/pubs.acs.org\/jprobs\/article-pdf\/25\/9\/4859\/66346406\/acs.jproteome.6c00389.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/pubs.acs.org\/jprobs\/article-pdf\/25\/9\/4859\/66346406\/acs.jproteome.6c00389.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,4]],"date-time":"2026-09-04T15:05:09Z","timestamp":1788534309000},"score":1,"resource":{"primary":{"URL":"https:\/\/pubs.acs.org\/jprobs\/article\/25\/9\/4859\/5237627\/LCM-Enriched-Proteomic-Characterization-of"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7,31]]},"references-count":42,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2026,7,31]]},"published-print":{"date-parts":[[2026,9,4]]}},"URL":"https:\/\/doi.org\/10.1021\/acs.jproteome.6c00389","relation":{},"ISSN":["1535-3893","1535-3907"],"issn-type":[{"value":"1535-3893","type":"print"},{"value":"1535-3907","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,7,31]]}}}