{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,10]],"date-time":"2026-08-10T14:41:59Z","timestamp":1786372919785,"version":"build-2736575974"},"reference-count":53,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"12","funder":[{"DOI":"10.13039\/100007388","name":"Compagnia di San Paolo","doi-asserted-by":"publisher","award":["ROL 9849"],"award-info":[{"award-number":["ROL 9849"]}],"id":[{"id":"10.13039\/100007388","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100014865","name":"Fondation Maladies Rares","doi-asserted-by":"crossref","award":["LAM-RD_20170304"],"award-info":[{"award-number":["LAM-RD_20170304"]}],"id":[{"id":"10.13039\/100014865","id-type":"DOI","asserted-by":"crossref"}]},{"name":"National Research Agency","award":["ANR-17-CE17-0012-01"],"award-info":[{"award-number":["ANR-17-CE17-0012-01"]}]},{"name":"Investments for the Future Laboratory of Excellence SIGNALIFE","award":["ANR-11-LABX-0028-01"],"award-info":[{"award-number":["ANR-11-LABX-0028-01"]}]},{"DOI":"10.13039\/501100002915","name":"Fondation pour la Recherche M\u00e9dicale","doi-asserted-by":"crossref","award":["ING20140129210"],"award-info":[{"award-number":["ING20140129210"]}],"id":[{"id":"10.13039\/501100002915","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100002915","name":"Fondation pour la Recherche M\u00e9dicale","doi-asserted-by":"crossref","award":["SPF20150934219"],"award-info":[{"award-number":["SPF20150934219"]}],"id":[{"id":"10.13039\/501100002915","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100002915","name":"Fondation pour la Recherche M\u00e9dicale","doi-asserted-by":"crossref","award":["DEQ20180339193"],"award-info":[{"award-number":["DEQ20180339193"]}],"id":[{"id":"10.13039\/501100002915","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100002915","name":"Fondation pour la Recherche M\u00e9dicale","doi-asserted-by":"crossref","award":["FDT201805005509"],"award-info":[{"award-number":["FDT201805005509"]}],"id":[{"id":"10.13039\/501100002915","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["CJASN"],"published-print":{"date-parts":[[2020,12]]},"abstract":"<jats:sec>\n                    <jats:title>Background and objectives<\/jats:title>\n                    <jats:p>Patients with membranous nephropathy can have circulating autoantibodies against membrane-bound (phospholipase A2 receptor 1 [PLA2R1] and thrombospondin type-1 domain containing 7A [THSD7A]) and intracellular (aldose reductase, SOD2, and \u03b1-enolase) podocyte autoantigens. We studied their combined association with clinical outcomes.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Design, setting, participants, &amp; measurements<\/jats:title>\n                    <jats:p>\n                      Serum levels of anti-PLA2R1, anti-THSD7A, anti-aldose reductase, anti-SOD2, and anti\u2212\u03b1-enolase autoantibodies were determined in 285 patients at diagnosis and during follow-up using standardized and homemade assays. An eGFR&gt;60 ml\/min per 1.73 m\n                      <jats:sup>2<\/jats:sup>\n                      and remission of proteinuria (&lt;0.3\/&lt;3.5 g per d) after 12 months were the outcomes of interest.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      At diagnosis, 182 (64%), eight (3%), and 95 (33%) patients were anti-PLA2R1\n                      <jats:sup>+<\/jats:sup>\n                      , anti-THSD7A\n                      <jats:sup>+<\/jats:sup>\n                      , and double negative, respectively. The prevalence of a detectable antibody to at least one intracellular antigen was similarly distributed in patients who were anti-PLA2R1\n                      <jats:sup>+<\/jats:sup>\n                      (\n                      <jats:italic toggle=\"yes\">n<\/jats:italic>\n                      =118, 65%) and double negative (\n                      <jats:italic toggle=\"yes\">n<\/jats:italic>\n                      =64, 67%). Positivity for anti-PLA2R1, anti-SOD2, and anti\u2013\u03b1-enolase antibodies and higher titers at diagnosis were associated with poor clinical outcome independently to each other. Combined positivity for anti-PLA2R1, anti-SOD2, and anti\u2212\u03b1-enolase was associated with highest risk of poor outcome (odds ratio, 5.5; 95% confidence interval, 1.2 to 24;\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      =0.01). In Kaplan\u2013Meier analysis, patients who were anti-PLA2R1\n                      <jats:sup>+<\/jats:sup>\n                      \/anti-SOD2\n                      <jats:sup>+<\/jats:sup>\n                      or anti-PLA2R1\n                      <jats:sup>+<\/jats:sup>\n                      \/anti\u2212\u03b1-enolase\n                      <jats:sup>+<\/jats:sup>\n                      had lower eGFR at 12 months compared with patients who were anti-PLA2R1\n                      <jats:sup>+<\/jats:sup>\n                      \/anti-SOD2\n                      <jats:sup>\u2212<\/jats:sup>\n                      or anti\u2212\u03b1-enolase\n                      <jats:sup>\u2212<\/jats:sup>\n                      . Predictive tests (net reclassification index and area under the curve\u2013receiver-operating characteristic analysis) showed that combined assessment of antibodies improved classification of outcome in 22%\u201334% of cases for partial remission of proteinuria and maintenance of normal eGFR. For patients with nephrotic syndrome at diagnosis, anti-SOD2 positivity and high anti-PLA2R1 titer were associated with a lack of complete remission. Patients who were anti-PLA2R1\n                      <jats:sup>\u2212<\/jats:sup>\n                      \/anti-intracellular antigens\n                      <jats:sup>\u2212<\/jats:sup>\n                      had the lowest proteinuria and the highest eGFR at diagnosis and the lowest risk of lower eGFR at 12 months. Epitope spreading was present in 81% of patients who were anti-PLA2R1\n                      <jats:sup>+<\/jats:sup>\n                      and was associated with increased positivity for intracellular antigens and poor eGFR at diagnosis and 12 months.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Combined serological analysis of autoantibodies targeting membrane-bound and intracellular autoantigens identifies patients with poor clinical outcomes.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.2215\/cjn.02500220","type":"journal-article","created":{"date-parts":[[2020,11,30]],"date-time":"2020-11-30T14:00:34Z","timestamp":1606744834000},"page":"1762-1776","source":"Crossref","is-referenced-by-count":30,"title":["Multi-Autoantibody Signature and Clinical Outcome in Membranous Nephropathy"],"prefix":"10.2215","volume":"15","clinical-trial-number":[{"clinical-trial-number":"nct02199145","registry":"10.18810\/clinical-trials-gov"}],"author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3659-9062","authenticated-orcid":false,"given":"Gian Marco","family":"Ghiggeri","sequence":"first","affiliation":[{"name":"Department of Pediatric and Hemato-Oncology Science, Institute Giannina Gaslini Scientific Institute for Research, Hospitalization and Healthcare, Nephrology, Dialysis and Transplantation Unit, Genoa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Barbara","family":"Seitz-Polski","sequence":"additional","affiliation":[{"name":"University C\u00f4te d\u2019Azur, National Centre for Scientific Research, Institute of Molecular and Cellular Pharmacology, Valbonne Sophia Antipolis, Nice, France"},{"name":"Department of Immunology, University C\u00f4te d\u2019Azur, Nice Hospital, Nice, France"},{"name":"Centre de R\u00e9f\u00e9rence Maladies Rares Syndrome N\u00e9phrotique Idiopathique, CHU de Nice, Universit\u00e9 C\u00f4te d\u2019Azur, Nice, France"},{"name":"Unit\u00e9 de Recherche Clinique de la C\u00f4te d\u2019Azur (UR2CA), Universit\u00e9 C\u00f4te d\u2019Azur, Nice, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joana","family":"Justino","sequence":"additional","affiliation":[{"name":"University C\u00f4te d\u2019Azur, National Centre for Scientific Research, Institute of Molecular and Cellular Pharmacology, Valbonne Sophia Antipolis, Nice, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christelle","family":"Zaghrini","sequence":"additional","affiliation":[{"name":"University C\u00f4te d\u2019Azur, National Centre for Scientific Research, Institute of Molecular and Cellular Pharmacology, Valbonne Sophia Antipolis, Nice, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christine","family":"Payr\u00e9","sequence":"additional","affiliation":[{"name":"University C\u00f4te d\u2019Azur, National Centre for Scientific Research, Institute of Molecular and Cellular Pharmacology, Valbonne Sophia Antipolis, Nice, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vesna","family":"Brglez","sequence":"additional","affiliation":[{"name":"University C\u00f4te d\u2019Azur, National Centre for Scientific Research, Institute of Molecular and Cellular Pharmacology, Valbonne Sophia Antipolis, Nice, France"},{"name":"Department of Immunology, University C\u00f4te d\u2019Azur, Nice Hospital, Nice, France"},{"name":"Centre de R\u00e9f\u00e9rence Maladies Rares Syndrome N\u00e9phrotique Idiopathique, CHU de Nice, Universit\u00e9 C\u00f4te d\u2019Azur, Nice, France"},{"name":"Unit\u00e9 de Recherche Clinique de la C\u00f4te d\u2019Azur (UR2CA), Universit\u00e9 C\u00f4te d\u2019Azur, Nice, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guillaume","family":"Dolla","sequence":"additional","affiliation":[{"name":"University C\u00f4te d\u2019Azur, National Centre for Scientific Research, Institute of Molecular and Cellular Pharmacology, Valbonne Sophia Antipolis, Nice, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alberto","family":"Sinico","sequence":"additional","affiliation":[{"name":"Department of Medicine and Surgery, University of Bicocca, Milan, Italia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesco","family":"Scolari","sequence":"additional","affiliation":[{"name":"Nephrology and Dialysis Unit, University of Brescia, Montichiari Hospital, Montichiari, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Augusto","family":"Vaglio","sequence":"additional","affiliation":[{"name":"Department of Clinical Medicine, Nephrology and Health Sciences, University of Parma, Parma, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0203-0129","authenticated-orcid":false,"given":"Marco","family":"Prunotto","sequence":"additional","affiliation":[{"name":"School of Pharmaceutical Sciences, University of Geneva, Geneva, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giovanni","family":"Candiano","sequence":"additional","affiliation":[{"name":"Institute Giannina Gaslini Scientific Institute for Research, Hospitalization and Healthcare, Molecular Nephrology Laboratory, Genoa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonella","family":"Radice","sequence":"additional","affiliation":[{"name":"Microbiology Institute, ASST Santi Paolo e Carlo, S. Carlo Borromeo Hospital, Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maurizio","family":"Bruschi","sequence":"additional","affiliation":[{"name":"Institute Giannina Gaslini Scientific Institute for Research, Hospitalization and Healthcare, Molecular Nephrology Laboratory, Genoa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9239-518X","authenticated-orcid":false,"given":"G\u00e9rard","family":"Lambeau","sequence":"additional","affiliation":[{"name":"University C\u00f4te d\u2019Azur, National Centre for Scientific Research, Institute of Molecular and Cellular Pharmacology, Valbonne Sophia Antipolis, Nice, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"on behalf of The Italian Study Group for Membranous 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