{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,29]],"date-time":"2025-12-29T11:12:03Z","timestamp":1767006723024,"version":"build-2065373602"},"reference-count":39,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2025,5,4]],"date-time":"2025-05-04T00:00:00Z","timestamp":1746316800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100009687","name":"Wroclaw Medical University","doi-asserted-by":"publisher","award":["IDUB.A507.24.028","SUBZ.A500.25.019"],"award-info":[{"award-number":["IDUB.A507.24.028","SUBZ.A500.25.019"]}],"id":[{"id":"10.13039\/501100009687","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>Background: Anti-PAR 1 (protease-activated receptor 1) and anti-ACE 2 (angiotensin 2-converting enzyme 2) antibodies are a kind of non-HLA (human leukocyte antigens) antibodies postulated to be of significance in autoimmunological diseases and organ transplantation. Methods: We assessed anti-PAR 1 and anti-ACE 2 antibody levels in patients with membranous nephropathy n= 18, focal and segmental glomerulosclerosis (FSGS) n = 25, lupus nephritis (LN) n = 17, IgA nephropathy n = 14, mesangial proliferative (non-IgA) glomerulonephritis n = 6, c-ANCA (cytoplasmic anti-neutrophil cytoplasmic antibodies) vasculitis n = 40, p (perinuclear)-ANCA vasculitis n = 16, and compared them with a healthy control group n = 22. Next, we observed the clinical course of the patients (creatinine, total protein, and albumin) up to 2 years and correlated the results with the level of antibodies. Results: The anti-PAR 1 antibody level was lower in membranous nephropathy and FSGS compared to the control group. Anti-PAR 1 antibody levels were higher in secondary compared to primary glomerulonephritis. Both anti-PAR 1 and anti-ACE 2 antibody levels correlated positively (in focal and segmental glomerulosclerosis) or negatively (in lupus nephritis) with total protein and albumin at different time points of observation. Anti-PAR 1 and anti-ACE 2 antibody levels correlated also with creatinine level at one time point of observation in IgA nephropathy. Anti-PAR 1 and anti-ACE 2 antibodies correlated with each other in membranous nephropathy, FSGS, and p- and c-ANCA vasculitis (p &lt; 0.05). Conclusions: The anti-PAR 1 antibody level was lower in membranous nephropathy and focal and segmental glomerulosclerosis compared to the control group. Anti-PAR 1 antibody levels tend to be higher in secondary compared to primary glomerulonephritis.<\/jats:p>","DOI":"10.3390\/jcm14093178","type":"journal-article","created":{"date-parts":[[2025,5,4]],"date-time":"2025-05-04T20:10:27Z","timestamp":1746389427000},"page":"3178","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["The Influence of Anti-PAR 1 and Anti-ACE 2 Antibody Levels on the Course of Specific Glomerulonephritis Types"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1248-081X","authenticated-orcid":false,"given":"Maciej","family":"Szymczak","sequence":"first","affiliation":[{"name":"Clinical Department of Nephrology, Transplantation Medicine and Internal Diseases Wroclaw Medical University, 50-556 Wroclaw, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Harald","family":"Heidecke","sequence":"additional","affiliation":[{"name":"CellTrend Gmbh, Im Biotechnologiepark 3 TGZ II, 14943 Luckenwalde, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marcelina","family":"\u017babi\u0144ska","sequence":"additional","affiliation":[{"name":"Department of Preclinical Sciences, Pharmacology and Medical Diagnostics, Faculty of Medicine, Wroc\u0142aw University of Science and Technology, 58-376 Wroclaw, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"\u0141ucja","family":"Janek","sequence":"additional","affiliation":[{"name":"Statistical Analysis Center, Wroclaw Medical University, 50-368 Wroclaw, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jakub","family":"Wronowicz","sequence":"additional","affiliation":[{"name":"Statistical Analysis Center, Wroclaw Medical University, 50-368 Wroclaw, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2812-4702","authenticated-orcid":false,"given":"Krzysztof","family":"Kujawa","sequence":"additional","affiliation":[{"name":"Statistical Analysis Center, Wroclaw Medical University, 50-368 Wroclaw, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-7297-8717","authenticated-orcid":false,"given":"Kai","family":"Schulze-Forster","sequence":"additional","affiliation":[{"name":"CellTrend Gmbh, Im Biotechnologiepark 3 TGZ II, 14943 Luckenwalde, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Karolina","family":"Marek-Bukowiec","sequence":"additional","affiliation":[{"name":"Clinical Department of Nephrology, Transplantation Medicine and Internal Diseases Wroclaw Medical University, 50-556 Wroclaw, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5477-2020","authenticated-orcid":false,"given":"Tomasz","family":"Go\u0142\u0119biowski","sequence":"additional","affiliation":[{"name":"Clinical Department of Nephrology, Transplantation Medicine and Internal Diseases Wroclaw Medical University, 50-556 Wroclaw, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0588-1551","authenticated-orcid":false,"given":"Miros\u0142aw","family":"Banasik","sequence":"additional","affiliation":[{"name":"Clinical Department of Nephrology, Transplantation Medicine and Internal Diseases Wroclaw Medical University, 50-556 Wroclaw, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,5,4]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Szymczak, M., Heidecke, H., \u017babi\u0144ska, M., Janek, \u0141., Wronowicz, J., Kujawa, K., Bukowiec-Marek, K., Go\u0142\u0119biowski, T., Skalec, K., and Schulze-Forster, K. (2024). The influence of anti-ETAR and anti-CXCR3 antibody levels on the course of specific glomerulonephritis types. J. Clin. Med., 13.","DOI":"10.3390\/jcm13247752"},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Sorohan, B.M., Baston, C., Tacu, D., Buc\u0219a, C., \u021aincu, C., Vizireanu, P., Sinescu, I., and Constantinescu, I. (2022). Non-HLA Antibodies in Kidney Transplantation: Immunity and Genetic Insights. Biomedicines, 10.","DOI":"10.3390\/biomedicines10071506"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"558","DOI":"10.1056\/NEJMoa035717","article-title":"Angiotensin II type 1-receptor activating antibodies in renal-allograft rejection","volume":"352","author":"Dragun","year":"2005","journal-title":"N. Engl. J. Med."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1","DOI":"10.2478\/aite-2024-0017","article-title":"Angiotensin II Type 2 Receptor Antibodies in Glomerular Diseases","volume":"72","author":"Szymczak","year":"2024","journal-title":"Arch. Immunol. Ther. Exp."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"603","DOI":"10.1161\/ATVBAHA.123.320185","article-title":"Thrombomodulin Switches Signaling and Protease-Activated Receptor 1 Cleavage Specificity of Thrombin","volume":"44","author":"Biswas","year":"2024","journal-title":"Arterioscler. Thromb. Vasc. Biol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"111413","DOI":"10.1016\/j.cellsig.2024.111413","article-title":"Targeting renal damage: The ACE2\/Ang-(1-7)\/mas axis in chronic kidney disease","volume":"124","author":"Zheng","year":"2024","journal-title":"Cell Signal."},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Bagang, N., Gupta, K., Singh, G., Kanuri, S.H., and Mehan, S. (2023). Protease-activated receptors in kidney diseases: A comprehensive review of pathological roles, therapeutic outcomes and challenges. Rev. Chem. Biol. Interact., 377.","DOI":"10.1016\/j.cbi.2023.110470"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"327","DOI":"10.1038\/nrneph.2011.51","article-title":"Inflammatory molecules and pathways in the pathogenesis of diabetic nephropathy","volume":"7","year":"2011","journal-title":"Nat. Rev. Nephrol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1357","DOI":"10.1093\/cvr\/cvy284","article-title":"Proteinase-activated receptor 1 antagonism ameliorates experimental pulmonary hypertension","volume":"115","author":"Kuwabara","year":"2019","journal-title":"Cardiovasc. Res."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"611","DOI":"10.1161\/HYPERTENSIONAHA.111.173229","article-title":"Proteinase-activated receptors 1 and 2 exert opposite effects on renal renin release","volume":"58","author":"Gerl","year":"2011","journal-title":"Hypertension"},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Andersson, L.I., Sj\u00f6str\u00f6m, D.J., Quach, H.Q., H\u00e4gerstr\u00f6m, K., Hurler, L., Kajd\u00e1csi, E., Cervenak, L., Proh\u00e1szka, Z., Toonen, E.J.M., and Mohlin, C. (2024). Storage of Transfusion Platelet Concentrates Is Associated with Complement Activation and Reduced Ability of Platelets to Respond to Protease-Activated Receptor-1 and Thromboxane A2 Receptor. Int. J. Mol. Sci., 25.","DOI":"10.3390\/ijms25021091"},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Das, M., Ithychanda, S.S., and Plow, E.F. (2022). Histone 2B Facilitates Plasminogen-Enhanced Endothelial Migration through Protease-Activated Receptor 1 (PAR1) and Protease-Activated Receptor 2 (PAR2). Biomolecules, 12.","DOI":"10.3390\/biom12020211"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"996","DOI":"10.1111\/jth.15642","article-title":"Thrombin in complex with dabigatran can still interact with PAR-1 via exosite-I and instigate loss of vascular integrity","volume":"20","author":"Agten","year":"2022","journal-title":"J. Thromb. Haemost."},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Waasdorp, M., Duitman, J., Florquin, S., and Spek, C.A. (2016). Protease-activated receptor-1 deficiency protects against streptozotocin-induced diabetic nephropathy in mice. Sci. Rep., 6.","DOI":"10.1038\/srep33030"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1016\/j.jphs.2017.09.002","article-title":"A protease-activated receptor-1 antagonist protects against podocyte injury in a mouse model of nephropathy","volume":"135","author":"Guan","year":"2017","journal-title":"J. Pharmacol. Sci."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"233","DOI":"10.1002\/jcp.22249","article-title":"Thrombin down-regulates the TGF-beta-mediated synthesis of collagen and fibronectin by human proximal tubule epithelial cells through the EPCR-dependent activation of PAR-1","volume":"225","author":"Bae","year":"2010","journal-title":"J. Cell. Physiol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"F1140","DOI":"10.1152\/ajprenal.00460.2016","article-title":"Protease-activated receptors in kidney disease progression","volume":"311","author":"Palygin","year":"2016","journal-title":"Am. J. Physiol. Renal. Physiol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"265","DOI":"10.1016\/j.kint.2023.02.031","article-title":"Podocyte protease activated receptor 1 stimulation in mice produces focal segmental glomerulosclerosis mirroring human disease signaling events","volume":"104","author":"May","year":"2023","journal-title":"Kidney Int."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"e15343","DOI":"10.14814\/phy2.15343","article-title":"Role of protease-activated receptor-1 (PAR-1) in the glomerular filtration barrier integrity","volume":"10","author":"Medipally","year":"2022","journal-title":"Physiol. Rep."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"2618","DOI":"10.1681\/ASN.2016070789","article-title":"Thrombin-Induced Podocyte Injury Is Protease-Activated Receptor Dependent","volume":"28","author":"Sharma","year":"2017","journal-title":"J. Am. Soc. Nephrol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"zqae030","DOI":"10.1093\/function\/zqae030","article-title":"PAR1-mediated Non-periodical Synchronized Calcium Oscillations in Human Mesangial Cells","volume":"5","author":"Stefanenko","year":"2024","journal-title":"Function"},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Simon, M., L\u00fccht, C., Hosp, I., Zhao, H., Wu, D., Heidecke, H., Witowski, J., Budde, K., Riemekasten, G., and Catar, R. (2021). Autoantibodies from Patients with Scleroderma Renal Crisis Promote PAR-1 Receptor Activation and IL-6 Production in Endothelial Cells. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms222111793"},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Sikorska, D., Kami\u0144ska, D., Catar, R., Banasik, M., Heidecke, H., Schulze-Forster, K., Korybalska, K., Rutkowski, R., \u0141uczak, J., and Jab\u0142ecki, J. (2022). Non-HLA Antibodies in Hand Transplant Recipients Are Connected to Multiple Acute Rejection Episodes and Endothelial Activation. J. Clin. Med., 11.","DOI":"10.3390\/jcm11030833"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1164","DOI":"10.1055\/a-2205-0014","article-title":"Protease-Activated Receptor-1 IgG Autoantibodies in Patients with COVID-19","volume":"124","author":"Reinshagen","year":"2024","journal-title":"Thromb. Haemost."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"515","DOI":"10.1161\/01.HYP.0000196268.08909.fb","article-title":"Angiotensin-converting enzyme 2 and angiotensin-(1-7): An evolving story in cardiovascular regulation","volume":"47","author":"Ferrario","year":"2006","journal-title":"Hypertension."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1902416","DOI":"10.1183\/13993003.02416-2019","article-title":"Angiotensin converting enzyme 2 and angiotensin (1-7) axis in pulmonary arterial hypertension","volume":"56","author":"Sandoval","year":"2020","journal-title":"Eur. Respir. J."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"839","DOI":"10.4239\/wjd.v12.i6.839","article-title":"New perspectives on angiotensin-converting enzyme 2 and its related diseases","volume":"12","author":"Liu","year":"2021","journal-title":"World J. Diabetes."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"74","DOI":"10.5527\/wjn.v4.i1.74","article-title":"ACE and ACE2 in kidney disease","volume":"4","author":"Mizuiri","year":"2015","journal-title":"World J. Nephrol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"3231","DOI":"10.2174\/0929867324666170414162841","article-title":"Circulating ACE2 in Cardiovascular and Kidney Diseases","volume":"24","author":"Anguiano","year":"2017","journal-title":"Curr. Med. Chem."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"52","DOI":"10.1016\/j.jim.2012.12.010","article-title":"Development of an enzymatic assay for the detection of neutralizing antibodies against therapeutic angiotensin-converting enzyme 2 (ACE2)","volume":"389","author":"Liao","year":"2013","journal-title":"J. Immunol. Methods"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"647","DOI":"10.1038\/s41423-020-0426-7","article-title":"Human monoclonal antibodies block the binding of SARS-CoV-2 spike protein to angiotensin converting enzyme 2 receptor","volume":"17","author":"Chen","year":"2020","journal-title":"Cell. Mol. Immunol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"457","DOI":"10.1002\/acr2.11423","article-title":"Presence and Implications of Anti-Angiotensin Converting Enzyme-2 Immunoglobulin M Antibodies in Anti-Melanoma-Differentiation-Associated 5 Dermatomyositis","volume":"4","author":"Mecoli","year":"2022","journal-title":"ACR. Open Rheumatol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"275","DOI":"10.1053\/j.akdh.2024.03.009","article-title":"Focal Segmental Glomerulosclerosis","volume":"31","author":"Suresh","year":"2024","journal-title":"Adv. Kidney Dis. Health"},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Pan, Y., Chen, S., Wu, L., Xing, C., Mao, H., Liang, H., and Yuan, Y. (2024). Animal models of membranous nephropathy: More choices and higher similarity. Front. Immunol., 15.","DOI":"10.3389\/fimmu.2024.1412826"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"e24961","DOI":"10.1002\/jcla.24961","article-title":"Association between anti-endothelial antigen antibodies and allograft rejection in kidney transplantation","volume":"37","author":"Lee","year":"2023","journal-title":"J. Clin. Lab. Anal."},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Bruschi, M., Candiano, G., Petretto, A., Angeletti, A., Meroni, P.L., Prunotto, M., and Ghiggeri, G.M. (2024). Technology Innovation for Discovering Renal Autoantibodies in Autoimmune Conditions. Int. J. Mol. Sci., 25.","DOI":"10.20944\/preprints202408.1027.v1"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"110454","DOI":"10.1016\/j.clim.2025.110454","article-title":"Stimulation of endothelin-1 production by autoantibodies present in patients with scleroderma renal crisis","volume":"273","author":"Wang","year":"2025","journal-title":"Clin. Immunol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"119387","DOI":"10.1016\/j.lfs.2021.119387","article-title":"Xanthenone, ACE2 activator, counteracted gentamicin-induced nephrotoxicity in rats: Impact on oxidative stress and ACE2\/Ang-(1-7) signaling","volume":"275","author":"Elgendy","year":"2021","journal-title":"Life Sci."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"21655","DOI":"10.18632\/oncotarget.25069","article-title":"Vorapaxar treatment reduces mesangial expansion in streptozotocin-induced diabetic nephropathy in mice","volume":"9","author":"Waasdorp","year":"2018","journal-title":"Oncotarget"}],"container-title":["Journal of Clinical Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2077-0383\/14\/9\/3178\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T17:26:57Z","timestamp":1760030817000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2077-0383\/14\/9\/3178"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,5,4]]},"references-count":39,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2025,5]]}},"alternative-id":["jcm14093178"],"URL":"https:\/\/doi.org\/10.3390\/jcm14093178","relation":{},"ISSN":["2077-0383"],"issn-type":[{"type":"electronic","value":"2077-0383"}],"subject":[],"published":{"date-parts":[[2025,5,4]]}}}