{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,3]],"date-time":"2026-11-03T20:15:28Z","timestamp":1793736928069,"version":"4.6.1"},"reference-count":42,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2021,1,25]],"date-time":"2021-01-25T00:00:00Z","timestamp":1611532800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["ascpt.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clinical Translational Sci"],"published-print":{"date-parts":[[2021,5]]},"abstract":"<jats:sec>\n                    <jats:title>Abstract<\/jats:title>\n                    <jats:p>\n                      To assess whether NLRP3 gene promoter methylation was able to discriminate glucocorticoid (GC)\u2010resistant from GC\u2010sensitive idiopathic nephrotic syndrome (INS), patients with minimal change disease (MCD) or focal segmental glomerulosclerosis (FSGS), we measured the methylation level of NLRP3 promoter in DNA from peripheral blood cells of 10 adult patients with GC\u2010resistant FSGS already in hemodialysis and 18 patients with GC\u2010sensitive INS (13 MCD\/5 FSGS) and in 21 pediatric patients with INS with MCD\/FSGS before starting any treatment. Association of NLRP3 inflammasome with GC resistance was recapitulated in vitro in monocytic cell lines (THP\u20101 and U937). In both adults and pediatric patients, NLRP3 promoter methylation was significantly reduced in GC\u2010resistant compared with GC\u2010sensitive patients. Indeed, NLRP3 methylation distinguished GC\u2010resistant and GC\u2010sensitive patients (area under the receiver operating characteristic curve [AUROC] 86.7% in adults,\n                      <jats:italic>p<\/jats:italic>\n                      \u00a0=\u00a00.00019, and 73.5% in children,\n                      <jats:italic>p<\/jats:italic>\n                      \u00a0=\u00a00.00097). NLRP3 knock\u2010down augmented sensitivity to GCs in THP\u20101 cells, whereas NLRP3 inflammasome activation lowered GC receptor concentration, increasing GC resistance in U937 cells. Our results uncovered a new biological mechanism by which patients with INS may acquire GC resistance, that could be used in future as a novel noninvasive diagnostic tool.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:label\/>\n                    <jats:p>\n                      <jats:boxed-text content-type=\"box\" position=\"anchor\">\n                        <jats:caption>\n                          <jats:title>Study Highlights<\/jats:title>\n                        <\/jats:caption>\n                        <jats:p>\n                          <jats:list list-type=\"simple\">\n                            <jats:list-item>\n                              <jats:p>\n                                <jats:bold>WHAT IS THE CURRENT KNOWLEDGE ON THE TOPIC?<\/jats:bold>\n                              <\/jats:p>\n                            <\/jats:list-item>\n                          <\/jats:list>\n                        <\/jats:p>\n                        <jats:p>\n                          \u2611 Approximately 80% of patients with idiopathic nephrotic syndrome (INS) respond to glucocorticoids, with the remaining 20% being steroid\u2010resistant.\n                          <jats:list list-type=\"simple\">\n                            <jats:list-item>\n                              <jats:p>\n                                <jats:bold>WHAT QUESTION DID THIS STUDY ADDRESS?<\/jats:bold>\n                              <\/jats:p>\n                            <\/jats:list-item>\n                          <\/jats:list>\n                        <\/jats:p>\n                        <jats:p>\n                          \u2611 Whether NLRP3 gene promoter methylation was able to discriminate glucocorticoid\u2010resistant from glucocorticoid (GC)\u2010sensitive INS.\n                          <jats:list list-type=\"simple\">\n                            <jats:list-item>\n                              <jats:p>\n                                <jats:bold>WHAT DOES THIS STUDY ADD TO OUR KNOWLEDGE?<\/jats:bold>\n                              <\/jats:p>\n                            <\/jats:list-item>\n                          <\/jats:list>\n                        <\/jats:p>\n                        <jats:p>\n                          \u2611 In both adults and children, NLRP3 promoter methylation was significantly reduced in leukocytes of patients with GC\u2010resistant compared with GC\u2010sensitive INS. NLRP3 inflammasome activation lowered GC receptor concentration and augmented GC resistance, whereas NLRP3 knockdown increased sensitivity to GCs in cell lines representative of monocytes (U937 and THP1).\n                          <jats:list list-type=\"simple\">\n                            <jats:list-item>\n                              <jats:p>\n                                <jats:bold>HOW MIGHT THIS CHANGE CLINICAL PHARMACOLOGY OR TRANSLATIONAL SCIENCE?<\/jats:bold>\n                              <\/jats:p>\n                            <\/jats:list-item>\n                          <\/jats:list>\n                        <\/jats:p>\n                        <jats:p>\u2611 Our findings uncovered a new biological mechanism whereby patients with INS may develop resistance to GCs that could be used in the future as a novel noninvasive diagnostic tool.<\/jats:p>\n                      <\/jats:boxed-text>\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/cts.12961","type":"journal-article","created":{"date-parts":[[2020,12,31]],"date-time":"2020-12-31T17:39:11Z","timestamp":1609436351000},"page":"964-975","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":22,"title":["Hypomethylation of NLRP3 gene promoter discriminates glucocorticoid\u2010resistant from glucocorticoid\u2010sensitive idiopathic nephrotic syndrome patients"],"prefix":"10.1111","volume":"14","author":[{"given":"Marianna","family":"Lucaf\u00f2","sequence":"first","affiliation":[{"name":"Institute for Maternal and Child Health I.R.C.C.S. Burlo Garofolo Trieste Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simona","family":"Granata","sequence":"additional","affiliation":[{"name":"Renal Unit Department of Medicine University Hospital of Verona Verona Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erik J.","family":"Bonten","sequence":"additional","affiliation":[{"name":"Hematological Malignancies Program Department of Pharmaceutical Sciences St. Jude Children\u2019s Research Hospital Memphis Tennessee USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert","family":"McCorkle","sequence":"additional","affiliation":[{"name":"Hematological Malignancies Program Department of Pharmaceutical Sciences St. Jude Children\u2019s Research Hospital Memphis Tennessee USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gabriele","family":"Stocco","sequence":"additional","affiliation":[{"name":"Department of Life Sciences University of Trieste Trieste Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chiara","family":"Caletti","sequence":"additional","affiliation":[{"name":"Renal Unit Department of Medicine University Hospital of Verona Verona Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Davide","family":"Selvestrel","sequence":"additional","affiliation":[{"name":"Department of Life Sciences University of Trieste Trieste Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alessio","family":"Cozzarolo","sequence":"additional","affiliation":[{"name":"Department of Life Sciences University of Trieste Trieste Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chan","family":"Zou","sequence":"additional","affiliation":[{"name":"Hematological Malignancies Program Department of Pharmaceutical Sciences St. Jude Children\u2019s Research Hospital Memphis Tennessee USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eva","family":"Cuzzoni","sequence":"additional","affiliation":[{"name":"Department of Life Sciences University of Trieste Trieste Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea","family":"Pasini","sequence":"additional","affiliation":[{"name":"Nephrology and Dialysis Unit Department of Pediatrics Azienda Ospedaliero Universitaria, Policlinico Sant'Orsola\u2010Malpighi Bologna Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giovanni","family":"Montini","sequence":"additional","affiliation":[{"name":"Pediatric Nephrology, Dialysis and Transplant Unit Fondazione Ca\u2019 Granda IRCCS, Policlinico di Milano Milano Italy"},{"name":"Giuliana and Bernardo Caprotti Chair of Pediatrics Department of Clinical Sciences and Community Health University of Milano Milano Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giovanni","family":"Gambaro","sequence":"additional","affiliation":[{"name":"Renal Unit Department of Medicine University Hospital of Verona Verona Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giuliana","family":"Decorti","sequence":"additional","affiliation":[{"name":"Institute for Maternal and Child Health I.R.C.C.S. 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