{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T15:11:35Z","timestamp":1792509095020,"version":"4.5.0"},"reference-count":24,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"3","content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":["JASN"],"published-print":{"date-parts":[[2021,3]]},"abstract":"<jats:sec>\n                    <jats:title>Significance Statement<\/jats:title>\n                    <jats:p>Approximately 20% of patients with lupus nephritis, the most common renal manifestation of systemic lupus erythematosus, show membranous lupus nephritis on kidney biopsy, and nearly 10% eventually develop ESKD. Recently, two proteins, Exostosin 1 and Exostosin 2 (EXT1\/EXT2), were shown to be present in a subset of membranous lupus nephritis kidney biopsy specimens. In an examination of 374 membranous lupus nephritis kidney biopsy specimens, the authors found 32.6% to be EXT1\/EXT2-positive. Kidney biopsy specimens from patients with EXT1\/EXT2-positive membranous lupus nephritis showed less chronicity features (glomerulosclerosis, interstitial fibrosis, and tubular atrophy) compared with those from EXT1\/EXT2-negative patients. EXT1\/EXT2-negative patients were also more likely to reach ESKD than EXT1\/EXT2-positive patients. These findings suggest that the presence of EXT1\/EXT2 is favorable, and that EXT1\/EXT2-positive patients have better renal outcomes compared with EXT1\/EXT2-negative patients.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>In patients with secondary (autoimmune) membranous nephropathy, two novel proteins, Exostosin 1 and Exostosin 2 (EXT1\/EXT2), are potential disease antigens, biomarkers, or both. In this study, we validate the EXT1\/EXT2 findings in a large cohort of membranous lupus nephritis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We conducted a retrospective cohort study of patients with membranous lupus nephritis, and performed immunohistochemistry studies on the kidney biopsy specimens against EXT1 and EXT2. Clinicopathologic features and outcomes of EXT1\/EXT2-positive versus EXT1\/EXT2-negative patients were compared.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Our study cohort included 374 biopsy-proven membranous lupus nephritis cases, of which 122 (32.6%) were EXT1\/EXT2-positive and 252 (67.4%) were EXT1\/EXT2-negative. EXT1\/EXT2-positive patients were significantly younger (\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      =0.01), had significantly lower serum creatinine levels (\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      =0.02), were significantly more likely to present with proteinuria \u22653.5 g\/24 h (\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      =0.009), and had significantly less chronicity features (glomerulosclerosis,\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      =0.001 or interstitial fibrosis and tubular atrophy,\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      &lt;0.001) on kidney biopsy. Clinical follow-up data were available for 160 patients, of which 64 (40%) biopsy results were EXT1\/EXT2-positive and 96 (60%) were EXT1\/EXT2-negative. The proportion of patients with class 3\/4 lupus nephritis coexisting with membranous lupus nephritis was not different between the EXT1\/EXT2-positive and EXT1\/EXT2-negative groups (25.0% versus 32.3%;\n                      <jats:italic toggle=\"yes\">P=<\/jats:italic>\n                      0.32). The patients who were EXT1\/EXT2-negative evolved to ESKD faster and more frequently compared with EXT1\/EXT2-positive patients (18.8% versus 3.1%;\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      =0.003).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>The prevalence of EXT1\/EXT2 positivity was 32.6% in our cohort of membranous lupus nephritis. Compared with EXT1\/EXT2-negative membranous lupus nephritis, EXT1\/EXT2-positive disease appears to represent a subgroup with favorable kidney biopsy findings with respect to chronicity indices. Cases of membranous lupus nephritis that are EXT1\/EXT2-negative are more likely to progress to ESKD compared with those that are EXT1\/EXT2-positive.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1681\/asn.2020081181","type":"journal-article","created":{"date-parts":[[2021,1,21]],"date-time":"2021-01-21T15:20:19Z","timestamp":1611242419000},"page":"695-706","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":87,"title":["In Patients with Membranous Lupus Nephritis, Exostosin-Positivity and Exostosin-Negativity Represent Two Different Phenotypes"],"prefix":"10.1681","volume":"32","author":[{"given":"Aishwarya","family":"Ravindran","sequence":"first","affiliation":[{"name":"Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marta","family":"Casal Moura","sequence":"additional","affiliation":[{"name":"Division of Pulmonary and Critical Care Medicine, Mayo Clinic, Rochester, Minnesota"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9952-209X","authenticated-orcid":false,"given":"Fernando C.","family":"Fervenza","sequence":"additional","affiliation":[{"name":"Division of Nephrology and Hypertension, Mayo Clinic, Rochester, Minnesota"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samih H.","family":"Nasr","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mariam P.","family":"Alexander","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mary E.","family":"Fidler","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Loren P.","family":"Herrera Hernandez","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pingchuan","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joseph P.","family":"Grande","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lynn D.","family":"Cornell","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lou Ann","family":"Gross","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vivian","family":"Negron","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Grace E.","family":"Jenson","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benjamin J.","family":"Madden","sequence":"additional","affiliation":[{"name":"Medical Genome Facility, Proteomics Core, Mayo Clinic, Rochester, Minnesota"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M. 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