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pmid:34424905
Proteomic analysis of serum samples of paracoccidioidomycosis patients with severe pulmonary sequel.
Amanda Ribeiro Dos Santos · Aline Dionizio · Mileni da Silva Fernandes · Marília Afonso Rabelo Buzalaf · Beatriz Pereira · Débora de Fátima Almeida Donanzam · Sergio Marrone Ribeiro · Anamaria Mello Miranda Paniago · Ricardo de Souza Cavalcante · Rinaldo Poncio Mendes · James Venturini
PLoS neglected tropical diseases · 2021 doi:10.1371/journal.pntd.0009714
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Complete file
{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:34424905", "kind": "science-record", "revision": 7, "content_hash": "sha256:5acc1cbcd259105efa3daa31e964f5c7557c51b2e12570dfdc5155b3acc4f6ca", "created_at": "2026-11-01T15:41:49Z", "updated_at": "2026-11-01T22:04:32Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Proteomic analysis of serum samples of paracoccidioidomycosis patients with severe pulmonary sequel.", "doi": "10.1371/journal.pntd.0009714", "pmid": "34424905", "authors": ["Amanda Ribeiro Dos Santos", "Aline Dionizio", "Mileni da Silva Fernandes", "Marília Afonso Rabelo Buzalaf", "Beatriz Pereira", "Débora de Fátima Almeida Donanzam", "Sergio Marrone Ribeiro", "Anamaria Mello Miranda Paniago", "Ricardo de Souza Cavalcante", "Rinaldo Poncio Mendes", "James Venturini"], "journal": "PLoS neglected tropical diseases", "year": 2021, "abstract": "BACKGROUND: Pulmonary sequelae (PS) in patients with chronic paracoccidioidomycosis (PCM) typically include pulmonary fibrosis and emphysema. Knowledge of the molecular pathways involved in PS of PCM is required for treatment and biomarker identification.\nMETHODOLOGY/PRINCIPAL FINDINGS: This non-concurrent cohort study included 29 patients with pulmonary PCM that were followed before and after treatment. From this group, 17 patients evolved to mild/ moderate PS and 12 evolved severe PS. Sera from patients were evaluated before treatment and at clinical cure, serological cure, and apparent cure. A nanoACQUITY UPLC-Xevo QT MS system and PLGS software were used to identify serum differentially expressed proteins, data are available via ProteomeXchange with identifier PXD026906. Serum differentially expressed proteins were then categorized using Cytoscape software and the Reactome pathway database. Seventy-two differentially expressed serum proteins were identified in patients with severe PS compared with patients with mild/moderate PS. Most proteins altered in severe PS were involved in wound healing, inflammatory response, and oxygen transport pathways. Before treatment and at clinical cure, signaling proteins participating in wound healing, complement cascade, cholesterol transport and retinoid metabolism pathways were downregulated in patients with severe PS, whereas signaling proteins in gluconeogenesis and gas exchange pathways were upregulated. At serological cure, the pattern of protein expression reversed. At apparent cure pathways related with tissue repair (fibrosis) became downregulated, and pathway related oxygen transport became upregulated. Additionally, we identified 15 proteins as candidate biomarkers for severe PS.\nCONCLUSIONS/SIGNIFICANCE: Development of severe PS is related to increased expression of proteins involved in glycolytic pathway and oxygen exchange), indicative of the greater cellular activity and replication associated with early dysregulation of wound healing and aberrant tissue repair. Our findings provide new targets to study mechanisms of PS in PCM, as well as potential biomarkers.", "claims": [{"id": "claim-method", "statement": "To determine differences serum proteins expression between PCM patients with severe and mild/moderate PS in each stage of clinical follow-up, ProteinLynx Global Server (PLGS) Expression E software was used, with p < 0.05 and p > 0.95 used to identify downregulation and upregulation of proteins, respectively, as reported earlier [40].", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:34424905", "locator": "sections[7] \"LC-MS/MS and bioinformatics analyses\" paragraph 2", "quote": "To determine differences serum proteins expression between PCM patients with severe and mild/moderate PS in each stage of clinical follow-up, ProteinLynx Global Server (PLGS) Expression E software was used, with p < 0.05 and p > 0.95 used to identify downregulation and upregulation of proteins, respectively, as reported earlier [40]."}], "state": "complete"}, {"id": "claim-data-access", "statement": "All relevant data are within the manuscript and its Supporting Information files.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:34424905", "locator": "sections[20] \"Data Availability\" paragraph 2", "quote": "All relevant data are within the manuscript and its Supporting Information files."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "partial", "objective": null, "steps": [{"id": "read_published_estimate", "order": 1, "name": "Read the published estimate from the source", "kind": "other", "state": "complete", "blocked_on": null, "description": "The claim, method and evidence span published with the source article.", "duration_hours": null, "parameters": {}, "inputs": ["source:pmid:34424905"], "outputs": ["the published estimate and its evidence"], "instruments": [], "reagents": []}, {"id": "obtain_source_data", "order": 2, "name": "Obtain the source data from the named repository", "kind": "data-preparation", "state": "complete", "blocked_on": null, "description": "The GEO series accession resolves and its sample accessions are listed. This lane did not download the dataset or read its licence.", "duration_hours": null, "parameters": {}, "inputs": ["data:geo:PXD026906"], "outputs": ["the source data with its repository provenance"], "instruments": [], "reagents": []}, {"id": "run_analysis", "order": 3, "name": "Run the published analysis", "kind": "analysis", "state": "blocked", "blocked_on": "method:group_comparison_mann_whitney", "description": "Apply the paper's statistical method to the resolved series and compare the result with the published target.", "duration_hours": null, "parameters": {}, "inputs": ["data:geo:PXD026906"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": ["step:run_analysis blocked on method:group_comparison_mann_whitney"]}, "data": {"state": "partial", "assets": [{"id": "source:pmid:34424905", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.1371/journal.pntd.0009714", "sha256": "sha256:9bda7eec581d6293cbbe590e834a041120ce686b16e1b24fecfd5b01c7f9d36b", "bytes": 65309, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "10.1371/journal.pntd.0009714", "version": null, "note": "Full article fetched from PMC; the checksum covers the rendered section body, not the original XML bytes.", "structure": {"pmcid": "PMC8425554", "source": "europe_pmc_fulltext", "coverage": "whole_body", "text_hash_scope": "rendered_section_body"}}, {"id": "data:geo:PXD026906", "role": "raw", "format": "geo-series", "media_type": "application/vnd.ncbi.geo-series+json", "uri": "https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=PXD026906", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "PXD026906", "version": null, "note": "All relevant data are within the manuscript and its Supporting Information files.", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "All relevant data are within the manuscript and its Supporting Information files.", "access_statement_kind": "data_availability_statement", "sample_accessions": [], "sample_count": null, "group_sizes": null, "group_sizes_basis": null, "platform": null, "taxon": null, "title": "Proteomic analysis of serum samples of paracoccidioidomycosis patients with severe pulmonary sequel", "resolution_checked_at": "2026-10-31T18:35:55Z", "resolution_check": "identifier_resolution_only_no_download_no_licence_read", "downloaded": false, "licence_read": false}}, {"id": "asset:table:pmid:34424905:1", "role": "table", "format": "jats-table", "media_type": "application/vnd.jats.table+json", "uri": null, "sha256": "sha256:b485a280c508376f11b8a24a312da897bf8df166dc83418f43e1257fea3498b7", "bytes": 1466, "access": "open", "state": "verified", "reader": "read_table", "reader_status": "available", "identifier": "section[5]/table-wrap[1]#pntd.0009714.t001", "version": null, "note": "Clinical aspects of paracoccidioidomycosis patients distributed according of pulmonar sequel (PS) intensity. N (%).", "structure": {"pmcid": "PMC8425554", "section_index": 5, "section_title": "Procedures", "row_count": 22, "column_count": 6}, "table": {"label": "Table 1", "caption": "Clinical aspects of paracoccidioidomycosis patients distributed according of pulmonar sequel (PS) intensity. N (%).", "rows": [["Clinical Aspects", "Patients (n = 29)", "Mild/moderate PS (n = 17)", "Severe PS (n = 12)", "p value"], ["Age (years) 1", "50", "56", "57", "0.8003"], ["Levels of severity 2", "Mild", "2 (6.9)", "2 (11.7)", "0 (0)", "1.000"], ["Moderate", "23 (79.3)", "13 (76.4)", "10 (83.3)"], ["Severe", "4 (13.8)", "2 (11.7)", "2 (16.6)"], ["Affected organs 2", "Adrenal", "3 (10.3)", "1 (5.88)", "2 (16.6)", "0.367"], ["CNS", "3 (10.3)", "3 (17.6)", "0 (0)", "0.186"], ["Mucosa", "5 (51.7)", "9(52.9)", "6 (50)", "0.586"], ["Skin", "1 (3.4)", "1 (5.88)", "0 (0)", "0.586"], ["Lung", "29 (100)", "17 (100)", "12 (100)", "UR"], ["Larynx", "5 (17.2)", "2 (11.7)", "3(25)", "0.329"], ["Lymphnode", "4 (13.8)", "4 (23.5)", "0 (0)", "0.100"], ["Bone", "1 (3.4)", "0 (0)", "1 (8.33)", "0.413"], ["Antifungal treatment 2", "CMX", "17 (58.6)", "11 (64.7)", "6 (50)", "0.5368"], ["CMX–ITC", "4 (13.8)", "4 (23.5)", "0 (0)"], ["ITC", "3 (10.3)", "1 (5.88)", "2 (16.6)"], ["ITC- CMX", "2 (6.9)", "0 (0)", "2 (16.6)"], ["Others", "3 (10.3)", "2 (11.7)", "1 (8.3)"], ["Time of treatment (months) 1", "38", "28", "44", "0.2871"], ["Time for clinical cure (days) 1", "142", "149", "126", "0.2687"], ["Time for serological cure (days) 1 . 3", "530", "314.5", "825", "0.2679"], ["DID 1", "1:16", "1:16", "1:8", "0.9463"]], "row_count": 22, "column_count": 6, "numeric_cells": 88, "header_rows": 1, "locator": "section[5]/table-wrap[1]#pntd.0009714.t001"}}, {"id": "asset:table:pmid:34424905:2", "role": "table", "format": "jats-table", "media_type": "application/vnd.jats.table+json", "uri": null, "sha256": "sha256:228df5ee8f59bb078dc820fe3114c6bb14b423ac493f7aaf50953eb47b293935", "bytes": 3476, "access": "open", "state": "verified", "reader": "read_table", "reader_status": "available", "identifier": "section[7]/table-wrap[1]#pntd.0009714.t002", "version": null, "note": "Proteins with expression significantly altered in the serum of paracoccidioidomycosis patients with severe and mild/moderate pulmonary sequel (PS) as outcome in the moment of before treatment (S0).", "structure": {"pmcid": "PMC8425554", "section_index": 7, "section_title": "LC-MS/MS and bioinformatics analyses", "row_count": 58, "column_count": 4}, "table": {"label": "Table 2", "caption": "Proteins with expression significantly altered in the serum of paracoccidioidomycosis patients with severe and mild/moderate pulmonary sequel (PS) as outcome in the moment of before treatment (S0).", "rows": [["aAccess number", "Protein name", "PLGS Score", "bRatio (severe PS:mild/moderate PS)"], ["P68871", "Hemoglobin subunit beta", "5774", "2.34"], ["P69892", "Hemoglobin subunit gamma-2", "2216", "2.32"], ["P02042", "Hemoglobin subunit delta", "2216", "2.29"], ["P02100", "Hemoglobin subunit epsilon", "2216", "2.27"], ["P69891", "Hemoglobin subunit gamma-1", "2216", "2.25"], ["P69905", "Hemoglobin subunit alpha", "4673", "2.16"], ["P06733", "Alpha-enolase", "556", "1.30"], ["P09104", "Gamma-enolase", "556", "1.30"], ["P13929", 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["*P02763", "Alpha-1-acid glycoprotein 1", "493", "mild/moderate PS"], ["*P19652", "Alpha-1-acid glycoprotein 2", "1020", "mild/moderate PS"], ["*Q02985", "Complement factor H-related protein 3", "20", "mild/moderate PS"], ["*Q5SZK8", "FRAS1-related extracellular matrix protein 2", "12", "mild/moderate PS"], ["*P17301", "Integrin alpha-2", "37", "mild/moderate PS"], ["*O60229", "Kalirin", "37", "mild/moderate PS"], ["*Q86W24", "NACHT_ LRR and PYD domains-containing protein 14", "16", "mild/moderate PS"], ["*P05155", "Plasma protease C1 inhibitor", "192", "mild/moderate PS"], ["*O94827", "Pleckstrin homology domain-containing family G member 5", "72", "mild/moderate PS"], ["*Q9NZ71", "Regulator of telomere elongation helicase 1", "70", "mild/moderate PS"], ["*P02753", "Retinol-binding protein 4", "104", "mild/moderate PS"]], "row_count": 58, "column_count": 4, "numeric_cells": 172, "header_rows": 1, "locator": "section[7]/table-wrap[1]#pntd.0009714.t002"}}, {"id": "asset:table:pmid:34424905:3", "role": "table", "format": "jats-table", "media_type": "application/vnd.jats.table+json", "uri": null, "sha256": "sha256:ee8b3ffb62082110af27a198196533df49dd4ccac01be5dfb8852ae31dc71b47", "bytes": 2261, "access": "open", "state": "verified", "reader": "read_table", "reader_status": "available", "identifier": "section[7]/table-wrap[2]#pntd.0009714.t003", "version": null, "note": "Proteins with expression significantly altered in the serum of paracoccidioidomycosis patients with severe and mild/moderate pulmonary sequel (PS) as outcome in the moment of clinical cure (S1).", "structure": {"pmcid": "PMC8425554", "section_index": 7, "section_title": "LC-MS/MS and bioinformatics analyses", "row_count": 39, "column_count": 4}, "table": {"label": "Table 3", "caption": "Proteins with expression significantly altered in the serum of paracoccidioidomycosis patients with severe and mild/moderate pulmonary sequel (PS) as outcome in the moment of clinical cure (S1).", "rows": [["aAccess number", "Protein name", "PLGS Score", "bRatio (severe PS:mild/moderate PS)"], ["P69905", "Hemoglobin subunit alpha", "2896", "1.72"], ["P02787", "Serotransferrin", "44194", "1.30"], ["P00738", "Haptoglobin", "21516", "1.16"], ["P00739", "Haptoglobin-related protein", "10216", "1.14"], ["P68871", "Hemoglobin subunit beta", "4951", "1.11"], ["P04217", "Alpha-1B-glycoprotein", "948", "0.93"], ["P01011", "Alpha-1-antichymotrypsin", "2832", "0.90"], ["P08603", "Complement factor H", "284", "0.88"], ["P19827", "Inter-alpha-trypsin inhibitor heavy chain H1", "328", "0.87"], ["P02774", "Vitamin D-binding protein", "2264", "0.87"], ["P02751", "Fibronectin", "94", "0.86"], ["P00747", "Plasminogen", "308", "0.85"], ["P02749", "Beta-2-glycoprotein 1", "905", "0.84"], ["P0C0L4", "Complement C4-A", "470", "0.84"], ["P0C0L5", "Complement C4-B", "470", "0.84"], ["P05546", "Heparin cofactor 2", "94", "0.84"], ["P04004", "Vitronectin", "763", "0.82"], ["P01024", "Complement C3", 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["P27169", "Serum paraoxonase/arylesterase 1", "1266", "Mild/moderate PS"]], "row_count": 39, "column_count": 4, "numeric_cells": 117, "header_rows": 1, "locator": "section[7]/table-wrap[2]#pntd.0009714.t003"}}, {"id": "asset:table:pmid:34424905:4", "role": "table", "format": "jats-table", "media_type": "application/vnd.jats.table+json", "uri": null, "sha256": "sha256:b3ace37943dc64273c84f974146d63d5147eb7b7e0158d5983dd5dbf76b9d936", "bytes": 2705, "access": "open", "state": "verified", "reader": "read_table", "reader_status": "available", "identifier": "section[7]/table-wrap[3]#pntd.0009714.t004", "version": null, "note": "Proteins with expression significantly altered in the serum of paracoccidioidomycosis patients with severe and mild/moderate pulmonary sequel (PS) as outcome in moment of serological cure (S2).", "structure": {"pmcid": "PMC8425554", "section_index": 7, "section_title": "LC-MS/MS and bioinformatics analyses", "row_count": 47, "column_count": 4}, "table": {"label": "Table 4", "caption": "Proteins with expression significantly altered in the serum of paracoccidioidomycosis patients with severe and mild/moderate pulmonary sequel (PS) as outcome in moment of serological cure (S2).", "rows": [["aAccess number", "Protein name", "PLGS Score", "bRatio (severe PS:mild/moderate PS)"], ["P02751", "Fibronectin", "799", "2.32"], ["P05155", "Plasma protease C1 inhibitor", "561", "1.82"], ["P00739", "Haptoglobin-related protein", "7979", "1.39"], ["P00738", "Haptoglobin", "20464", "1.35"], ["Q14624", "Inter-alpha-trypsin inhibitor heavy chain H4", "56", "1.34"], ["Q5T013", "Putative hydroxypyruvate isomerase", "140", "1.32"], ["P02787", "Serotransferrin", "58693", "1.25"], ["P02765", "Alpha-2-HS-glycoprotein", "1410", "1.22"], ["P02750", "Leucine-rich alpha-2-glycoprotein", "280", "1.21"], ["P13929", "Beta-enolase", "1050", "1.19"], ["P09104", "Gamma-enolase", "1050", "1.19"], ["P01024", "Complement C3", "21361", "1.16"], ["P00751", "Complement factor B", "1405", "1.15"], ["P02790", "Hemopexin", "5861", "1.15"], ["P04004", "Vitronectin", "693", "1.15"], ["P04196", "Histidine-rich glycoprotein", "110", "1.15"], ["P05546", "Heparin cofactor 2", "158", "1.12"], ["P00747", "Plasminogen", "465", "1.09"], ["P01011", "Alpha-1-antichymotrypsin", "2056", "1.08"], ["P02647", "Apolipoprotein A-I", "8940", "1.07"], ["P10909", "Clusterin", "1717", "1.07"], ["P20742", "Pregnancy zone protein", "301", "1.06"], ["P02774", "Vitamin D-binding protein", "2536", "1.05"], ["P00450", "Ceruloplasmin", "1149", "1.04"], ["P01023", "Alpha-2-macroglobulin", "9840", "1.03"], ["P06727", "Apolipoprotein A-IV", "126", "0.91"], ["P0C0L4", "Complement C4-A", "470", "0.91"], ["P0C0L5", "Complement C4-B", "460", "0.90"], ["P02760", "Protein AMBP", "336", "0.89"], ["P01009", "Alpha-1-antitrypsin", "6126", "0.84"], ["P02749", "Beta-2-glycoprotein 1", "1341", "0.78"], ["P02763", "Alpha-1-acid glycoprotein 1", "225", "0.61"], ["P27169", "Serum paraoxonase/arylesterase 1", "726", "0.57"], ["P69905", "Hemoglobin subunit alpha", "386", "0.52"], ["P19652", "Alpha-1-acid glycoprotein 2", "123", "0.51"], ["P68871", "Hemoglobin subunit beta", "2416", "0.50"], ["P02042", "Hemoglobin subunit delta", "1332", "0.47"], ["P02100", "Hemoglobin subunit epsilon", "1332", "0.46"], ["P69891", "Hemoglobin subunit gamma-1", "1332", "0.46"], ["P69892", "Hemoglobin subunit gamma-2", "1332", "0.45"], ["P08697", "Alpha-2-antiplasmin", "689", "Severe PS*"], ["P02652", "Apolipoprotein A-II", "436", "Severe PS"], ["P02649", "Apolipoprotein E", "158", "Severe PS"], ["P0DJI8", "Serum amyloid A-1 protein", "3449", "Severe PS"], ["P0DJI9", "Serum amyloid A-2 protein", "544", "Severe PS"], ["Q15166", "Serum paraoxonase/lactonase 3", "4", "mild/moderate PS"]], "row_count": 47, "column_count": 4, "numeric_cells": 144, "header_rows": 1, "locator": "section[7]/table-wrap[3]#pntd.0009714.t004"}}, {"id": "asset:table:pmid:34424905:5", "role": "table", "format": "jats-table", "media_type": 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name", "PLGS Score", "bRatio (Severe PS:mild/moderate PS)"], ["P69905", "Hemoglobin subunit alpha", "1823", "1.30"], ["P02790", "Hemopexin", "6961", "1.06"], ["P08603", "Complement factor H", "486", "0.88"], ["P00738", "Haptoglobin", "22790", "0.87"], ["P01023", "Alpha-2-macroglobulin", "6037", "0.85"], ["P00739", "Haptoglobin-related protein", "9541", "0.84"], ["P20742", "Pregnancy zone protein", "432", "0.84"], ["P00751", "Complement factor B", "1196", "0.83"], ["P02749", "Beta-2-glycoprotein 1", "1413", "0.78"], ["P02774", "Vitamin D-binding protein", "1889", "0.77"], ["P00747", "Plasminogen", "337", "0.76"], ["P04004", "Vitronectin", "705", "0.76"], ["Q96PD5", "N-acetylmuramoyl-L-alanine amidase", "144", "0.74"], ["P01042", "Kininogen-1", "732", "0.74"], ["P0C0L4", "Complement C4-A", "489", "0.73"], ["P0C0L5", "Complement C4-B", "488", "0.73"], ["P00734", "Prothrombin", "541", "0.73"], ["P05546", "Heparin cofactor 2", "93", "0.72"], ["P02766", "Transthyretin", "2160", "0.72"], ["P01011", "Alpha-1-antichymotrypsin", "1925", "0.71"], ["P04217", "Alpha-1B-glycoprotein", "999", "0.68"], ["P00450", "Ceruloplasmin", "2315", "0.66"], ["P01024", "Complement C3", "13144", "0.66"], ["P19827", "Inter-alpha-trypsin inhibitor heavy chain H1", "1036", "0.66"], ["P01019", "Angiotensinogen", "117", "0.65"], ["P02760", "Protein AMBP", "495", "0.65"], ["P02787", "Serotransferrin", "45136", "0.65"], ["Q14624", "Inter-alpha-trypsin inhibitor heavy chain H4", "147", "0.64"], ["P19823", "Inter-alpha-trypsin inhibitor heavy chain H2", "1325", "0.63"], ["Q5T013", "Putative hydroxypyruvate isomerase", "72", "0.60"], ["P02656", "Apolipoprotein C-III", "4030", "0.59"], ["P02765", "Alpha-2-HS-glycoprotein", "2620", "0.58"], ["P10909", "Clusterin", "823", "0.58"], ["P06727", "Apolipoprotein A-IV", "155", "0.56"], ["P01009", "Alpha-1-antitrypsin", "4246", "0.55"], ["P02647", "Apolipoprotein A-I", "8083", "0.52"], ["P01008", "Antithrombin-III", "156", "Severe PS*"], ["P43652", "Afamin", 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