Multiple Processes May Involve in the IgG4-RD Pathogenesis: An Integrative Study via Proteomic and Transcriptomic Analysis.

{"sci_version": "1.0", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:32973752", "kind": "science-record", "revision": 6, "content_hash": "sha256:18ef65f6a4f72fdfa8fd9ec793b34b841bfa7bf45600556aa370de6e6bf9729c", "created_at": "2026-11-01T15:41:11Z", "updated_at": "2026-11-01T21:23:50Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Multiple Processes May Involve in the IgG4-RD Pathogenesis: An Integrative Study via Proteomic and Transcriptomic Analysis.", "doi": "10.3389/fimmu.2020.01795", "pmid": "32973752", "authors": ["Shaozhe Cai", "Yu Chen", "ShengYan Lin", "Cong Ye", "Fang Zheng", "Lingli Dong"], "journal": "Frontiers in immunology", "year": 2020, "abstract": "Immunoglobulin G4-related disease (IgG4-RD) is a newly defined disease entity, while the exact pathogenesis is still not clear. Identifying the characters of IgG4-RD in proteomic and transcriptomic aspects will be critical to investigate the potential pathogenic mechanisms of IgG4-RD. We performed proteomic analysis realized with iTRAQ technique for serum samples from eight treatment-naive IgG4-RD patients and eight healthy volunteers, and tissue samples from two IgG4-RD patients and two non-IgG4-RD patients. Transcriptomic data (GSE40568 and GSE66465) was obtained from the GEO Dataset for validation. The weighted correlation network analysis (WGCNA) was applied to detect the gene modules correlated with IgG4-RD. KEGG pathway analysis was used to investigate pathways enriched in IgG4-RD samples. As a result, a total of 980 differentially expressed proteins (DEPs) in tissue and 94 DEPs in serum were identified between IgG4-RD and control groups. Three hundred fifty-four and two hundred forty-seven genes that most correlated with IgG4-RD were detected by WGCNA analysis in tissue and PBMC, respectively. We also found that DEPs in IgG4-RD samples were enriched in several immune-related activities including bacterial/viral infections and platelet activation as well as some immune related signaling pathways. In conclusion, we identified multiple processes/factors and several signaling pathways that may involve in the IgG4-RD pathogenesis, and found out some potential therapeutic targets for IgG4-RD.", "claims": [{"id": "claim-method", "statement": "Log2 transformed data were used to calculate the difference of proteins between IgG4-RD and HC samples with “t-test” function in R package (version 3.5.1).", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:32973752", "locator": "sections[10] \"Statistical Analysis\" paragraph 2", "quote": "Log2 transformed data were used to calculate the difference of proteins between IgG4-RD and HC samples with “t-test” function in R package (version 3.5.1)."}], "state": "complete"}, {"id": "claim-data-access", "statement": "Data of GSE40568 and GSE66465 can be downloaded from Gene Expression Omnibus Dataset (GEO Dataset: http://www.ncbi.nlm.nih.gov/geo/). The proteomic data is available from the corresponding author on reasonable request.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:32973752", "locator": "sections[20] \"Data Availability Statement\" paragraph 2", "quote": "Data of GSE40568 and GSE66465 can be downloaded from Gene Expression Omnibus Dataset (GEO Dataset: http://www.ncbi.nlm.nih.gov/geo/). The proteomic data is available from the corresponding author on reasonable request."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "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:32973752"], "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:GSE40568"], "outputs": ["the source data with its repository provenance"], "instruments": [], "reagents": []}, {"id": "run_analysis", "order": 3, "name": "Run the published analysis", "kind": "analysis", "state": "complete", "blocked_on": null, "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:GSE40568"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": []}, "data": {"state": "partial", "assets": [{"id": "source:pmid:32973752", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.3389/fimmu.2020.01795", "sha256": "sha256:85675686643941753b4f439d041e259ecf0200f119b560d470bdc4ce76533fe1", "bytes": 47408, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "10.3389/fimmu.2020.01795", "version": null, "note": "Full article fetched from PMC; the checksum covers the rendered section body, not the original XML bytes.", "structure": {"pmcid": "PMC7468437", "source": "europe_pmc_fulltext", "coverage": "whole_body", "text_hash_scope": "rendered_section_body"}}, {"id": "data:geo:GSE40568", "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=GSE40568", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE40568", "version": null, "note": "Data of GSE40568 and GSE66465 can be downloaded from Gene Expression Omnibus Dataset (GEO Dataset: http://www.ncbi.nlm.nih.gov/geo/). 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The proteomic data is available from the corresponding author on reasonable request.", "access_statement_kind": "data_availability_statement", "sample_accessions": ["GSM1389608", "GSM1389609", "GSM1389610", "GSM1389611", "GSM1389612", "GSM1389613", "GSM1389614", "GSM1389615", "GSM1389616", "GSM1389617", "GSM1389618", "GSM1389619", "GSM1389620"], "sample_count": 13, "group_sizes": null, "group_sizes_basis": null, "platform": "570", "taxon": "Homo sapiens", "title": "DNA microarray analysis of labial salivary glands in IgG4-related disease – comparison with Sjögren’s syndrome", "resolution_checked_at": "2026-11-01T15:39:54Z", "resolution_check": "identifier_resolution_only_no_download_no_licence_read", "downloaded": false, "licence_read": false}}, {"id": "data:geo:GSE66465", "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=GSE66465", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE66465", "version": null, "note": "Data of GSE40568 and GSE66465 can be downloaded from Gene Expression Omnibus Dataset (GEO Dataset: http://www.ncbi.nlm.nih.gov/geo/). 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"50–60", "Submandibular glands, lymph nodes", "Serum"]], "row_count": 9, "column_count": 4, "numeric_cells": 16, "header_rows": 1, "locator": "section[4]/table-wrap[1]#T1"}}, {"id": "asset:table:pmid:32973752:2", "role": "table", "format": "jats-table", "media_type": "application/vnd.jats.table+json", "uri": null, "sha256": "sha256:e774bd535e2829f490f9d68e06a8d9dc31b1b9ea97fecc00d74f0eaf77f0bd55", "bytes": 2118, "access": "open", "state": "verified", "reader": "read_table", "reader_status": "available", "identifier": "section[15]/table-wrap[1]#T2", "version": null, "note": "KEGG terms related to infectious process enriched in IgG4-RD tissue proteomic data.", "structure": {"pmcid": "PMC7468437", "section_index": 15, "section_title": "Potential Infection and Infection-Related Responses May Be the Trigger in IgG4-RD", "row_count": 15, "column_count": 4}, "table": {"label": "Table 2", "caption": "KEGG terms related to infectious process enriched in IgG4-RD tissue proteomic data.", "rows": [["Pathway ID", "KEGG term", "Associated proteins", "P-value"], ["KEGG:05143", "African trypanosomiasis", "FAS, GNAQ, IL18, LAMA4, PLCB1, PLCB2, PRKCB, VCAM1", "0.0010"], ["KEGG:05146", "Amoebiasis", "CASP3, GNA11, GNAQ, LAMA4, LAMB3, PLCB1, PLCB2, PRKACB, PRKCB, RAB5C, SERPINB9, TLR2", "0.0159"], ["KEGG:05100", "Bacterial invasion of epithelial cells", "ARPC1B, ARPC2, ARPC3, ARPC5, CDH1, DNM3, ELMO1, ELMO3, RHOG, SEPT1, WAS", "0.0050"], ["KEGG:05142", "Chagas disease American trypanosomiasis", "C1QB, CD3E, CD3G, FAS, GNA11, GNAO1, GNAQ, PLCB1, PLCB2, PPP2CB, PPP2R1B, TLR2", "0.0331"], ["KEGG:05120", "Epithelial cell signaling in Helicobacter pylori infection", "ADAM17, ATP6V0C, ATP6V1G2, CASP3, CSK, F11R, LYN, NOD1, PLCG2, TJP1", "0.0079"], ["KEGG:05170", "Human immunodeficiency virus 1 infection", "AP1G2, AP1S3, APOBEC3C, APOBEC3F, ATM, CASP3, CD3E, CD3G, CD4, CFL1, CFL2, FAS, GNA11, GNAO1, GNAQ, GNG2, GNG7, HLA-E, LIMK1, MAP2K1, PLCG2, PRKCB, RAC2, RPS6KB2, SAMHD1, TLR2, TRADD, TRIM5", "0.0001"], ["KEGG:05134", "Legionellosis", "CASP3, CR1, HSF1, HSPA6, IL18, PYCARD, RAB1A, TLR2", "0.0177"], ["KEGG:05140", "Leishmaniasis", "CR1, CYBB, HLA-DQA2, HLA-DQB1, HLA-DRA, ITGA4, PRKCB, PTPN6, TLR2", "0.0447"], ["KEGG:05144", "Malaria", "CR1, IL18, ITGAL, SDC2, THBS1, TLR2, VCAM1", "0.0282"], ["KEGG:05130", "Pathogenic Escherichia coli infection", "ARPC1B, ARPC2, ARPC3, ARPC5, CDH1, EZR, KRT18, TUBA4A, TUBAL3, TUBB1, TUBB4B, WAS", "0.0001"], ["KEGG:05132", "Salmonella infection", "ARPC1B, ARPC2, ARPC3, ARPC5, IL18, KLC3, KLC4, PFN1, PKN1, PYCARD, RHOG, TJP1, WAS", "0.0020"], ["KEGG:05131", "Shigellosis", "ARPC1B, ARPC2, ARPC3, ARPC5, ELMO1, ELMO3, NOD1, PFN1, RHOG, UBE2D2, WAS", "0.0018"], ["KEGG:05110", "Vibrio cholerae infection", "ATP6V0C, ATP6V1G2, PLCG2, PRKACB, SLC12A2, TJP1, TJP2", "0.0311"], ["KEGG:05416", "Viral myocarditis", "CASP3, CXADR, DAG1, DMD, HLA-DQA2, HLA-DQB1, HLA-DRA, HLA-E, ITGAL, RAC2", "0.0028"]], "row_count": 15, "column_count": 4, "numeric_cells": 39, "header_rows": 1, "locator": "section[15]/table-wrap[1]#T2"}}, {"id": "asset:table:pmid:32973752:3", "role": "table", "format": "jats-table", "media_type": "application/vnd.jats.table+json", "uri": null, "sha256": "sha256:dfe69839ad1ad96d52360e004b08122b09b70cc79fdb783b167d007cf5ddf43d", "bytes": 727, "access": "open", "state": "verified", "reader": "read_table", "reader_status": "available", "identifier": "section[15]/table-wrap[2]#T3", "version": null, "note": "KEGG terms related to infectious process enriched in “turquoise” module in IgG4-RD tissue transcriptomic data.", "structure": {"pmcid": "PMC7468437", "section_index": 15, "section_title": "Potential Infection and Infection-Related Responses May Be the Trigger in IgG4-RD", "row_count": 5, "column_count": 4}, "table": {"label": "Table 3", "caption": "KEGG terms related to infectious process enriched in “turquoise” module in IgG4-RD tissue transcriptomic data.", "rows": [["Pathway ID", "KEGG term", "Associated proteins", "P-value"], ["KEGG:05165", "Human papillomavirus infection", "AKT3, COL1A1, COL1A2, COL6A1, COL6A3, EGFR, FN1, FZD7, ITGA9, JAG1, LAMA2, LAMA4, LAMC1, THBS2", "0.0052"], ["KEGG:05100", "Bacterial invasion of epithelial cells", "CAV1, CAV2, FN1, MET, WASF2", "0.0112"], ["KEGG:05146", "Amoebiasis", "COL1A1, COL1A2, COL3A1, FN1, GNAL, LAMA2, LAMA4, LAMC1", "0.0004"], ["KEGG:05144", "Malaria", "CD36, HGF, MET, SDC2, THBS2", "0.0019"]], "row_count": 5, "column_count": 4, "numeric_cells": 9, "header_rows": 1, "locator": "section[15]/table-wrap[2]#T3"}}, {"id": "asset:table:pmid:32973752:4", "role": "table", "format": "jats-table", "media_type": "application/vnd.jats.table+json", "uri": null, "sha256": "sha256:3f95c9ec85e925c50d499e49f162290bf6a610f40bf48feee6ab475179472dcb", "bytes": 2919, "access": "open", "state": "verified", "reader": "read_table", "reader_status": "available", "identifier": "section[17]/table-wrap[1]#T4", "version": null, "note": "Signaling pathways and other potential pathogenic processes detected in IgG4-RD tissue transcriptomic data.", "structure": {"pmcid": "PMC7468437", "section_index": 17, "section_title": "Multiple Signaling Pathways May Participate the Pathogenesis of IgG4-RD", "row_count": 18, "column_count": 5}, "table": {"label": "Table 4", "caption": "Signaling pathways and other potential pathogenic processes detected in IgG4-RD tissue transcriptomic data.", "rows": [["Pathway ID", "KEGG term", "Associated proteins/genes", "P-value", "Data origin"], ["KEGG:04350", "TGF-beta signaling pathway", "BMP6, LTBP1, SMAD1, THBS1", "0.0409", "PBMC transcriptomic"], ["KEGG:04217", "Necroptosis", "HIST1H2AB, HIST1H2AE, HIST1H2AH, HIST1H2AI, HIST1H2AJ, HIST1H2AK, HIST1H2AL, HIST1H2AM, TNFAIP3", "0.0009", "PBMC transcriptomic"], ["KEGG:05203", "Viral carcinogenesis", "HIST1H2BB, HIST1H2BC, HIST1H2BG, HIST1H2BH, HIST1H2BI, HIST1H2BJ, HIST1H2BM, HIST1H2BN, HIST1H2BO, HIST1H4D, HIST2H2BE, HIST2H4A", "0.0001", "PBMC transcriptomic"], ["KEGG:05202", "Transcriptional misregulation in cancer", "CD14, HIST1H3A, HIST1H3B, HIST1H3F, HIST1H3H, HIST1H3J, MEIS1, SMAD1", "0.0081", "PBMC transcriptomic"], ["KEGG:04064", "NF-kappa B signaling pathway", "ATM, BTK, LYN, PARP1, PLCG2, PRKCB, TNFRSF11A, TRADD, UBE2I, VCAM1, ZAP70", "0.0471", "Tissue proteomic"], ["KEGG:04015", "Rap1 signaling pathway", "APBB1IP, CDH1, CSF1R, FLT1, FYB1, GNAO1, GNAQ, ITGA2B, ITGAL, MAP2K1, NGFR, PARD3, PDGFA, PDGFC, PDGFRA, PFN1, PLCB1, PLCB2, PRKCB, RAC2, RAP1A, SIPA1, SIPA1L3, THBS1, VASP", "0.0009", "Tissue proteomic"], ["KEGG:04140", "Autophagy", "DAPK1, GABARAPL1, HMGB1, MAP2K1, MTMR14, PIK3R4, PPP2CB, PRKACB, RPS6KB2, RRAGA, RRAGC, STX17, ULK2, WIPI1", "0.0371", "Tissue proteomic"], ["KEGG:04217", "Necroptosis", "CHMP1B, CHMP4C, CYBB, FAS, FTH1, FTL, H2AFX, H2AFY, H2AFY2, HIST2H2AB, HMGB1, PARP1, PYCARD, PYGM, TRADD, TYK2, ZBP1", "0.0289", "Tissue proteomic"], ["KEGG:05219", "Bladder cancer", "CDH1, DAPK1, MAP2K1, RPS6KA5, THBS1, TYMP", "0.0368", "Tissue proteomic"], ["KEGG:04010", "MAPK signaling pathway", "AKT3, EGFR, FGF2, FGF7, HGF, KITLG, MAP3K20, MET, NTRK2, PDGFD, PDGFRA, TGFBR2", "0.0115", "Tissue transcriptomic"], ["KEGG:04015", "Rap1 signaling pathway", "AKT3, DOCK4, EGFR, FGF2, FGF7, HGF, KITLG, MET, PDGFD, PDGFRA, SIPA1L2", "0.0013", "Tissue transcriptomic"], ["KEGG:04151", "PI3K-Akt signaling pathway", "AKT3, COL1A1, COL1A2, COL6A1, COL6A3, EGFR, FGF2, FGF7, FN1, GHR, GNG11, HGF, ITGA9, KITLG, LAMA2, LAMA4, LAMC1, MET, NTRK2, PDGFD, PDGFRA, THBS2", "<0.0001", "Tissue transcriptomic"], ["KEGG:05226", "Gastric cancer", "AKT3, EGFR, FGF2, FGF7, FZD7, HGF, MET, TGFBR2", "0.0059", "Tissue transcriptomic"], ["KEGG:05222", "Small cell lung cancer", "AKT3, FN1, LAMA2, LAMA4, LAMC1", "0.0276", "Tissue transcriptomic"], ["KEGG:05215", "Prostate cancer", "AKT3, EGFR, PDGFD, PDGFRA, PLAT", "0.0323", "Tissue transcriptomic"], ["KEGG:05205", "Proteoglycans in cancer", "AKT3, ANK2, CAV1, CAV2, COL21A1, DCN, EGFR, FGF2, FN1, FZD7, GPC3, HGF, LUM, MET, SDC2, TIMP3", "<0.0001", "Tissue transcriptomic"], ["KEGG:05218", "Melanoma", "AKT3, EGFR, FGF2, FGF7, HGF, MET, PDGFD, PDGFRA", "<0.0001", "Tissue transcriptomic"]], "row_count": 18, "column_count": 5, "numeric_cells": 40, "header_rows": 1, "locator": "section[17]/table-wrap[1]#T4"}}, {"id": "asset:table:pmid:32973752:5", "role": "table", "format": "jats-table", "media_type": "application/vnd.jats.table+json", "uri": null, "sha256": "sha256:9c0111502c82e77597113019c24136cb583ea3c781212d5ab1892190f55ffb04", "bytes": 2467, "access": "open", "state": "verified", "reader": "read_table", "reader_status": "available", "identifier": "section[18]/table-wrap[1]#T5", "version": null, "note": "Potential therapeutic targets and targeted drugs for IgG4-RD.", "structure": {"pmcid": "PMC7468437", "section_index": 18, "section_title": "Potential Therapeutic Target Identified by Tissue DEPs Related Biological Processes", "row_count": 20, "column_count": 4}, "table": {"label": "Table 5", "caption": "Potential therapeutic targets and targeted drugs for IgG4-RD.", "rows": [["Gene symbol", "Name", "Drugs (target type)", "Disease application"], ["Targets identified from KEGG terms"], ["RAC1", "Ras-related C3 botulinum toxin substrate 1", "EHT-1864 (Literature-reported target)", "Alzheimer disease"], ["ITGB1", "Integrin beta-1", "131I-radretumab (Clinical trial target)", "Non-small-cell lung cancer; Macular degeneration"], ["", "", "ATN-161(Clinical trial Target) *Target: Integrin alpha-5/beta-1", "Non-small-cell lung cancer; Renal cell carcinoma"], ["MAPK1", "Extracellular signal-regulated kinase 2", "CI-1040 (Clinical trial target)", "Artery stenosis; Pancreatic cancer"], ["MAPK3", "Extracellular signal-regulated kinase 1", "BVD-523 (Clinical trial Target)", "Solid tumor/cancer; Artery stenosis"], ["PRKCB", "Protein kinase C beta", "Enzastaurin (Clinical trial target)", "Diffuse large B-cell lymphoma; Lymphoma"], ["PRKCA", "Protein kinase C alpha", "Sodium phenylbutyrate (Successful target)", "Spinal muscular atrophy; Renal transplantation;"], ["PIK3CA", "Phosphatidylinositol 3-kinase catalytic subunit alpha", "BAY 80-6946 (Successful target)", "Follicular lymphoma; Non-hodgkin lymphoma"], ["PIK3CB", "Phosphatidylinositol 3-kinase catalytic subunit beta", "Buparlisib (Clinical trial target)", "Breast cancer; Pain"], ["PIK3CD", "Phosphatidylinositol 3-kinase catalytic subunit delta", "Idelalisib (Successful target)", "Follicular lymphoma; Small lymphocytic lymphoma"], ["PRKCG", "Protein kinase C gamma", "Midostaurin (Successful target)", "Acute myeloid leukemia; Systemic mastocytosis"], ["SRC", "Proto-oncogene tyrosine-protein kinase Src", "Herbimycin A (Successful target)", "Breast cancer; Ischemia"], ["Targets identified from GO Biological process terms"], ["NCK1", "NCK adaptor protein", "AX-024 (Clinical trial target)", "Multiple sclerosis"], ["PRKCD", "Protein kinase C delta", "KAI-9803 (Clinical trial target)", 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