Increased serum calpain activity is associated with HMGB1 levels in systemic sclerosis.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:32393322", "kind": "science-record", "revision": 8, "content_hash": "sha256:30d9c5f6efec47f2ec502a9598abd5034d677592e55457d995957a82fcfc0368", "created_at": "2026-11-01T15:41:01Z", "updated_at": "2026-11-01T22:44:50Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Increased serum calpain activity is associated with HMGB1 levels in systemic sclerosis.", "doi": "10.1186/s13075-020-02195-y", "pmid": "32393322", "authors": ["Ji-Na Zheng", "Yang Li", "Yue-Mei Yan", "Yong Yu", "Wen-Qi Shao", "Qiang Wang"], "journal": "Arthritis research & therapy", "year": 2020, "abstract": "BACKGROUND: Systemic sclerosis (SSc) or scleroderma is an intractable autoimmune disorder that affects multiple organs. The objectives were to investigate clinical correlations of serum calpain activity and high mobility group box 1 (HMGB1) levels with immunological and clinical traits.\nMETHODS: A total of 31 patients with SSc, 20 age- and gender-matched healthy control subjects (HC), and 10 patients with other connective tissue diseases (CTD) were recruited in the study. We measured serum calpain activity and HMGB1 levels and analyzed the datasets (GSE40839, GSE48149, GSE76808, GSE81292, GSE33463, and GSE58095) from Gene Expression Omnibus (GEO) database to explore the potential mechanism by which calpain exerts its function through bioinformatics methods.\nRESULTS: Serum calpain activity was significantly increased in patients with SSc compared with those in HC and in patients with CTD and was correlated with serum HMGB1 levels, modified Rodnan skin score, erythrocyte sedimentation rate, mean platelet volume, and plateletcrit. Notably, serum calpain activity and HMGB1 levels in SSc patients with interstitial lung disease (ILD) were significantly higher than those in SSc patients without ILD. Serum calpain activity and HMGB1 levels could be the independent risk factors for SSc-ILD and novel biomarkers in patients with SSc.\nCONCLUSION: This is the first study that reports increased serum calpain activity and the correlation between calpain and HMGB1 in patients with SSc or SSc-ILD. The serum calpain activity and HMGB1 levels may serve as measures of ILD in patients with SSc. Also, calpain and HMGB1 could be potential therapeutic targets for patients with SSc or SSc-ILD in the future.", "claims": [{"id": "claim-method", "statement": "Next, the differential expression analysis (Log2FC > |1|, p value < 0.05) of calpain-related genes was performed by comparing SSc or SSc-ILD samples to HC samples using the limma package.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:32393322", "locator": "sections[8] \"Data processing\" paragraph 2", "quote": "Next, the differential expression analysis (Log2FC > |1|, p value < 0.05) of calpain-related genes was performed by comparing SSc or SSc-ILD samples to HC samples using the limma package."}], "state": "complete"}, {"id": "claim-data-access", "statement": "Publicly available datasets were analyzed in this study. Datasets (GSE40839, GSE48149, GSE76808, GSE81292, GSE33463, and GSE58095) were downloaded from GEO (http://www.ncbi.nlm.nih.gov/geo/).", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:32393322", "locator": "sections[28] \"notes\" paragraph 1", "quote": "Publicly available datasets were analyzed in this study. Datasets (GSE40839, GSE48149, GSE76808, GSE81292, GSE33463, and GSE58095) were downloaded from GEO (http://www.ncbi.nlm.nih.gov/geo/)."}], "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:32393322"], "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:GSE33463"], "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:GSE33463"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": []}, "data": {"state": "partial", "assets": [{"id": "source:pmid:32393322", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.1186/s13075-020-02195-y", "sha256": "sha256:6c380fc79ee6c3aa0ddcd3269995e66e1943a5670e42ac55cb0f8786c6264275", "bytes": 41110, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "10.1186/s13075-020-02195-y", "version": null, "note": "Full article fetched from PMC; the checksum covers the rendered section body, not the original XML bytes.", "structure": {"pmcid": "PMC7216546", "source": "europe_pmc_fulltext", "coverage": "whole_body_without_references", "text_hash_scope": "rendered_section_body"}}, {"id": "data:geo:GSE33463", "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=GSE33463", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE33463", "version": null, "note": "Publicly available datasets were analyzed in this study. Datasets (GSE40839, GSE48149, GSE76808, GSE81292, GSE33463, and GSE58095) were downloaded from GEO (http://www.ncbi.nlm.nih.gov/geo/).", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "Publicly available datasets were analyzed in this study. 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Datasets (GSE40839, GSE48149, GSE76808, GSE81292, GSE33463, and GSE58095) were downloaded from GEO (http://www.ncbi.nlm.nih.gov/geo/).", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "Publicly available datasets were analyzed in this study. Datasets (GSE40839, GSE48149, GSE76808, GSE81292, GSE33463, and GSE58095) were downloaded from GEO (http://www.ncbi.nlm.nih.gov/geo/).", "access_statement_kind": "data_availability_statement", "sample_accessions": ["GSM2038267", "GSM2038268", "GSM2038269", "GSM2038270", "GSM2038271", "GSM2038272", "GSM2038273", "GSM2038274", "GSM2038275", "GSM2038276", "GSM2038277", "GSM2038278", "GSM2038279", "GSM2038280", "GSM2038281", "GSM2038282", "GSM2038283", "GSM2038284"], "sample_count": 18, "group_sizes": null, "group_sizes_basis": null, "platform": "571", "taxon": "Homo sapiens", "title": "Association of Interferon- and Transforming Growth Factor  -Regulated Genes and Macrophage Activation With Systemic Sclerosis-Related Progressive Lung Fibrosis", "resolution_checked_at": "2026-11-01T15:39:55Z", "resolution_check": "identifier_resolution_only_no_download_no_licence_read", "downloaded": false, "licence_read": false}}, {"id": "data:geo:GSE81292", "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=GSE81292", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE81292", "version": null, "note": "Publicly available datasets were analyzed in this study. Datasets (GSE40839, GSE48149, GSE76808, GSE81292, GSE33463, and GSE58095) were downloaded from GEO (http://www.ncbi.nlm.nih.gov/geo/).", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "Publicly available datasets were analyzed in this study. Datasets (GSE40839, GSE48149, GSE76808, GSE81292, GSE33463, and GSE58095) were downloaded from GEO (http://www.ncbi.nlm.nih.gov/geo/).", "access_statement_kind": "data_availability_statement", "sample_accessions": ["GSM2149850", "GSM2149851", "GSM2149852", "GSM2149853", "GSM2149854", "GSM2149855", "GSM2149856", "GSM2149857", "GSM2149858", "GSM2149859", "GSM2149860", "GSM2149861", "GSM2149862", "GSM2149863", "GSM2149864", "GSM2149865", "GSM2149866", "GSM2149867", "GSM2149868", "GSM2149869"], "sample_count": 20, "group_sizes": null, "group_sizes_basis": null, "platform": "18991", "taxon": "Homo sapiens", "title": "Expression of mRNA from lung tissue from Systemic Sclerosis patients with interstitial lung disease (SSc-ILD)  and healthy controls (HC)", "resolution_checked_at": "2026-11-01T15:39:55Z", "resolution_check": "identifier_resolution_only_no_download_no_licence_read", "downloaded": false, "licence_read": false}}, {"id": "asset:table:pmid:32393322:1", "role": "table", "format": "jats-table", "media_type": "application/vnd.jats.table+json", "uri": null, "sha256": "sha256:569ec2d4183554ed70e9954e9ea28c4d22fc33a6b41872ffb9c2047985d3ebcf", "bytes": 2063, "access": "open", "state": "verified", "reader": "read_table", "reader_status": "available", "identifier": "section[3]/table-wrap[1]#Tab1", "version": null, "note": "Laboratory and clinical characteristics of the patients and control subjects included in the study", "structure": {"pmcid": "PMC7216546", "section_index": 3, "section_title": "Patients and controls", "row_count": 31, "column_count": 6}, "table": {"label": "Table 1", "caption": "Laboratory and clinical characteristics of the patients and control subjects included in the study", "rows": [["Characteristics", "All SSc (n = 31)", "Non-ILD-SSc (n = 10)", "SSc-ILD (n = 21)", "Other CTD (n = 10)", "HC (n = 20)"], ["Age (mean ± SD)", "51 ± 13", "49 ± 14", "53 ± 12", "47 ± 11", "40 ± 11"], ["Female,n(%)", "27 (87)", "10 (91)", "17 (85)", "8 (80)", "17 (85)"], ["Course of disease (mean ± SD)", "8 ± 7", "8 ± 8", "9 ± 8", "NA"], ["lSSc/dSSc %", "55/45", "45/55", "60/40"], ["PAH,n(%)", "3 (10)", "0 (0)", "3 (15)"], ["Raynaud’s phenomenon,n(%)", "28 (90)", "9 (82)", "19 (45)"], ["Anti-Scl-70 antibody,n(%)", "13 (42)", "4 (36)", "9 (45)"], ["ANA,n(%)", "30 (97)", "10 (91)", "20 (100)"], ["Anti-RNP,n(%)", "8 (26)", "4 (36)", "4 (20)"], ["Anti-centromere,n(%)", "8 (26)", "2 (18)", "6 (30)"], ["mRSS (mean ± SD)n = 25", "12 ± 10", "21 ± 14", "10 ± 7"], ["Immunosuppressive therapy ever,n(%)", "11 (35)", "5 (45)", "6 (25)"], ["Cyclophosphamide,n(%)", "6 (19)", "3 (27)", "3 (15)"], ["Methotrexate,n(%)", "2 (6)", "0 (0)", "2 (5)"], ["Mycophenolate mofetil,n(%)", "3 (10)", "2 (18)", "1 (5)"], ["FVC % predicted,n = 17 (mean ± SD)", "74.5 ± 14.2", "78 ± 8.5", "75.6 ± 16.2"], ["DLCO% predicted,n = 8 (mean ± SD)", "74.2 ± 22.3", "70.9 ± 3.5", "76.2 ± 27.8"], ["FEV1/FVC%,n = 17 (mean ± SD)", "85.5 ± 11.6", "76.2 ± 7.5", "88.4 ± 11.1"], ["ESR, mm/h (mean ± SD)", "17.10 ± 11", "17.80 ± 14.36", "16.76 ± 9.13"], ["PLT, 109/L (mean ± SD)", "206 ± 67", "209.40 ± 79.98", "204.62 ± 61.60"], ["MPV, fL (mean ± SD)", "11.95 ± 1.49", "11.23 ± 1.95", "10.81 ± 1.24"], ["PDW, fL (mean ± SD)", "0.22 ± 0.07", "0.23 ± 0.08", "0.22 ± 0.07"], ["PCT, % (mean ± SD)", "31.17 ± 11.13", "34.69 ± 14.07", "29.49 ± 9.36"], ["P-LCR, % (mean ± SD)", "13.47 ± 3.30", "14.12 ± 4.50", "13.16 ± 2.63"], ["RA,n(%)", "NA", "1 (10)", "NA"], ["ANCA-associated vasculitis,n(%)", "1 (10)"], ["SLE,n(%)", "2 (20)"], ["SS,n(%)", "1 (10)"], ["Dermatomyositis,n(%)", "2 (20)"], ["Polymyositis,n(%)", "3 (30)"]], "row_count": 31, "column_count": 6, "numeric_cells": 93, "header_rows": 1, "locator": "section[3]/table-wrap[1]#Tab1"}}, {"id": "asset:table:pmid:32393322:2", "role": "table", "format": "jats-table", "media_type": "application/vnd.jats.table+json", "uri": null, "sha256": "sha256:06ddb57cff400172b1f3186261310188dd470eb89d12356e5ea00bd8841b389f", "bytes": 2293, "access": "open", "state": "verified", "reader": "read_table", "reader_status": "available", "identifier": "section[15]/table-wrap[1]#Tab2", "version": null, "note": "Clinical and laboratory characteristics of SSc patients according to serum calpain activity and HMGB1 levels", "structure": {"pmcid": "PMC7216546", "section_index": 15, "section_title": "Clinical and laboratory correlation", "row_count": 22, "column_count": 7}, "table": {"label": "Table 2", "caption": "Clinical and laboratory characteristics of SSc patients according to serum calpain activity and HMGB1 levels", "rows": [["Characteristics", "Calpainhigh, n = 10", "Calpainlow, n = 21", "p value", "HMGB-1high, n = 12", "HMGB-1low, n = 19", "p value"], ["Age (mean ± SD)", "48 ± 13", "53 ± 13", "0.311", "49 ± 14", "53 ± 12", "0.358"], ["Female,n(%)", "8 (80)", "19 (90)", "0.577", "11 (92)", "16 (84)", "0.958"], ["Course of disease (mean ± SD)", "10 ± 11", "7 ± 6", "0.299", "7 ± 2", "8 ± 2", "0.946"], ["dSSc/lSSc", "5/5", "12/9", "0.709", "8 (67)", "6 (32)", "0.075"], ["PAH,n(%)", "2 (20)", "3 (14)", "0.690", "4 (33)", "1 (5)", "0.060"], ["SSc-ILD,n(%)", "8 (80)", "16 (76)", "0.813", "11 (92)", "13 (68)", "0.201"], ["Raynaud’s phenomenon,n(%)", "9 (90)", "18 (86)", "0.734", "11 (92)", "16 (84)", "0.958"], ["Anti-Scl-70 antibody,n(%)", "1 (10)", "12 (57)", "0.020*", "5 (42)", "8 (42)", "0.981"], ["ANA,n(%)", "10 (100)", "20 (95)", "0.483", "12 (100)", "18 (95)", "0.999"], ["Anti-RNP,n(%)", "4 (40)", "4 (19)", "0.381", "4 (33)", "4 (21)", "0.676"], ["Anti-centromere,n(%)", "3 (30)", "5 (24)", "0.715", "5 (42)", "3 (16)", "0.206"], ["mRSS (mean ± SD)n = 26", "19 ± 13", "9 ± 6", "0.012*", "9 ± 5", "15 ± 12", "0.098"], ["FVC % predicted,n = 17 (mean ± SD)", "64.85 ± 35.29", "54.27 ± 35.40", "0.545", "52.63 ± 33.50", "63.80 ± 36.46", "0.472"], ["DLCO% predicted,n = 8 (mean ± SD)", "81.74 ± 32.99", "66.57 ± 11.25", "0.488", "61.35 ± 20.29", "80.79 ± 27.21", "0.387"], ["FEV1/FVC%n = 17 (mean ± SD)", "88.42 ± 15.84", "85.53 ± 8.49", "0.638", "83.58 ± 9.22", "88.97 ± 12.79", "0.344"], ["ESR, mm/h (mean ± SD)", "11.10 ± 5.04", "19.95 ± 11.77", "0.031*", "13.92 ± 8.45", "19.11 ± 11.90", "0.167"], ["Platelets count, 109/L (mean ± SD)", "201 ± 71", "209 ± 66", "0.772", "194 ± 83", "214 ± 56", "0.442"], ["MPV, fL (mean ± SD)", "11.59 ± 1.66", "10.64 ± 1.33", "0.096", "11.25 ± 1.82", "10.75 ± 1.25", "0.373"], ["PDW, fL (mean ± SD)", "0.22 ± 0.07", "0.22 ± 0.07", "0.867", "0.21 ± 0.08", "0.23 ± 0.06", "0.480"], ["PCT, % (mean ± SD)", "37.74 ± 11.69", "28.04 ± 9.62", "0.021*", "30.98 ± 12.95", "31.29 ± 10.20", "0.944"], ["P-LCR, % (mean ± SD)", "15.17 ± 3.94", "12.66 ± 2.68", "0.045*", "14.08 ± 4.01", "13.08 ± 2.81", "0.465"]], "row_count": 22, "column_count": 7, "numeric_cells": 136, "header_rows": 1, "locator": "section[15]/table-wrap[1]#Tab2"}}, {"id": "asset:table:pmid:32393322:3", "role": "table", "format": "jats-table", "media_type": "application/vnd.jats.table+json", "uri": null, "sha256": "sha256:5dddcc2634ca0ac82727ad5d6ce3078dbbc08ed7dd332694c990519918a85967", "bytes": 1605, "access": "open", "state": "verified", "reader": "read_table", "reader_status": "available", "identifier": "section[16]/table-wrap[1]#Tab3", "version": null, "note": "Univariate and multivariate logistic regression of clinical and laboratory parameters to ILD in patients with SSc", "structure": {"pmcid": "PMC7216546", "section_index": 16, "section_title": "Diagnostic value of serum calpain activity and HMGB1 levels", "row_count": 22, "column_count": 7}, "table": {"label": "Table 3", "caption": "Univariate and multivariate logistic regression of clinical and laboratory parameters to ILD in patients with SSc", "rows": [["Hub genes/clinical traits", "Univariate logistic regression", "Multivariate logistic regression"], ["OR", "95% CI", "p value", "OR", "95% CI", "p value"], ["Gender", "1.578", "0.218, 7.618", "0.929", "", "", ""], ["Age", "0.943", "0.878, 1.013", "0.108", "", "", ""], ["Course of disease", "0.991", "0.898, 1.093", "0.857", "", "", ""], ["Raynaud’s phenomenon", "0.421", "0.050, 3.532", "0.425", "", "", ""], ["Anti-Scl-70 antibody (+)", "2.121", "0.428, 10.515", "0.357", "", "", ""], ["ANA (+)", "0.970", "0.982, 1.0010", "0.834", "", "", ""], ["Anti-RNP (+)", "0.353", "0.066, 1.874", "0.221", "", "", ""], ["Anti-centromere (+)", "4.500", "0.471, 42.970", "0.191", "", "", ""], ["mRSS", "0.876", "0.770, 0.997", "0.044*", "0.917", "0.807, 1.042", "0.184"], ["FVC (%predict)", "1.003", "0.973, 1.033", "0.865", "", "", ""], ["DLCO (%predict)", "1.071", "0.934, 1.228", "0.325", "", "", ""], ["FEV1/FVC%", "1.087", "0.944, 1.253", "0.245", "", "", ""], ["ESR, mm/h", "0.991", "0.925, 1.062", "0.800", "", "", ""], ["PLT, 109/L", "0.999", "0.987, 1.010", "0.850", "", "", ""], ["MPV, fL", "0.829", "0.503, 1.365", "0.461", "", "", ""], ["PDW, fL", "0.282", "0.000, 21.236", "0.825", "", "", ""], ["PCT, %", "0.959", "0.895, 1.028", "0.235", "", "", ""], ["P-LCR, %", "0.916", 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