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Type IV collagen and laminin \u03b15\u03b22\u03b31 (laminin 521) within the GBM are two major target antigens in anti-GBM disease. Perlecan is a type of heparan sulphate proteoglycans, ubiquitously expressed in basement membranes. The present study aimed to investigate whether perlecan could be recognized by anti-GBM antibodies and further analysed the properties and clinical associations of anti-perlecan antibodies.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>A total of 108 patients diagnosed with anti-GBM disease between January 2000 and December 2018 were included in the study. Additionally, 100 patients with various active glomerular diseases were utilized as disease controls, along with 40 healthy controls. Immunoglobulin G (IgG) antibodies against perlecan were detected by enzyme-linked immunosorbent assay and immunoblot.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Circulating IgG antibodies against perlecan were detected in 18.5% (20\/108) of the anti-GBM patients but not in the healthy controls or other glomerular disease controls. Anti-perlecan IgG antibodies were predominantly of the IgG3 subclass. Patients with anti-perlecan autoantibodies had a higher prevalence of lung haemorrhage than those without (55.0% versus 26.1%; P\u00a0=\u00a0.012). A \u2018triple-positive\u2019 subgroup with anti-GBM disease was identified, who had circulating autoantibodies simultaneously against type IV collagen, laminin 521 and perlecan. This subgroup had the highest prevalence of lung haemorrhage [66.7% (10\/15)] and incidence of end-stage kidney disease events [93.3% (14\/15)], indicating a more aggressive immune-mediated tissue injury among these patients.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Perlecan expands the repertoire of target antigens in anti-GBM disease. The discovery of autoantibodies against perlecan identified a \u2018triple-positive\u2019 subgroup with a more severe clinical phenotype among patients with anti-GBM disease. The pathogenic role of autoimmunity against perlecan and the pathophysiology of the co-existence of three autoantibodies merit further investigation in the future.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/ndt\/gfaf153","type":"journal-article","created":{"date-parts":[[2025,8,10]],"date-time":"2025-08-10T11:41:04Z","timestamp":1754826064000},"page":"55-66","source":"Crossref","is-referenced-by-count":4,"title":["Perlecan is a novel target of autoantibodies in anti-glomerular basement membrane disease"],"prefix":"10.1093","volume":"41","author":[{"given":"Huang","family":"Kuang","sequence":"first","affiliation":[{"name":"Renal Division, Peking University First Hospital , Beijing ,","place":["China"]},{"name":"Institute of Nephrology, Peking University , Beijing ,","place":["China"]},{"name":"Key Laboratory of Renal Disease, Ministry of Health of China , Beijing ,","place":["China"]},{"name":"Key Laboratory of CKD Prevention and Treatment, Ministry of Education of China 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,","place":["China"]},{"name":"Key Laboratory of CKD Prevention and Treatment, Ministry of Education of China , Beijing ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nan","family":"Jiang","sequence":"additional","affiliation":[{"name":"Renal Division, Peking University First Hospital , Beijing ,","place":["China"]},{"name":"Institute of Nephrology, Peking University , Beijing ,","place":["China"]},{"name":"Key Laboratory of Renal Disease, Ministry of Health of China , Beijing ,","place":["China"]},{"name":"Key Laboratory of CKD Prevention and Treatment, Ministry of Education of China , Beijing ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dorin-Bogdan","family":"Borza","sequence":"additional","affiliation":[{"name":"Meharry Medical College Department of Microbiology, Immunology and Physiology, , Nashville, TN 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