{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T05:54:15Z","timestamp":1792130055089,"version":"4.4.0"},"reference-count":28,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2021,2,28]],"date-time":"2021-02-28T00:00:00Z","timestamp":1614470400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Annals of Neurology"],"published-print":{"date-parts":[[2021,5]]},"abstract":"<jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>This study was undertaken to describe a novel biomarker of germ cell tumor and associated paraneoplastic neurological syndrome (PNS).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Archival sera from patients with germ cell tumor\u2013associated PNS were evaluated. We identified a common autoantigen in a human testicular cancer cell line (TCam\u20102) by Western blot and mass spectrometry. Its identity was confirmed by recombinant\u2010protein Western blot, enzyme\u2010linked immunosorbent assay (ELISA), and cell\u2010based assay. Autoantibody specificity was confirmed by analyzing assorted control sera\/cerebrospinal fluid.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Leucine zipper 4 (LUZP4)\u2013immunoglobulin G (IgG) was detected in 28 patients' sera, 26 of whom (93%) were men. The median age at neurological symptom onset was 45\u2009years (range = 28\u201384). Median titer (ELISA) was 1:300 (1:50 to &gt;1:6,400, normal value &lt;\u20091:50). Coexistent kelchlike protein 11\u2013IgG was identified in 18 cases (64%). The most common presenting phenotype was rhombencephalitis (17\/28, 61%). Other presentations included limbic encephalitis (n = 5, 18%), seizures and\/or encephalitis (n = 2, 7%), and motor neuronopathy\/polyradiculopathy (n = 4, 14%). The most common malignancy among cancer\u2010evaluated PNS patients was seminoma (21\/27, 78%). Nine of the 21 seminomas detected by whole\u2010body fluorodeoxyglucose positron emission tomography scan (43%) were extratesticular. Both female patients had ovarian teratoma. Regressed testicular germ cell tumors were found in 4 patients. Exposure of T\u2010cell\u2013dendritic\u2010cell cocultures from chronic immunosuppression\u2010na\u00efve LUZP4\u2010IgG\u2013seropositive patients to recombinant LUZP4 protein evoked a marked increase in CD69 expression on both CD4+ and CD8+ T cells when compared to vehicle\u2010exposed and healthy control cultures.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Interpretation<\/jats:title>\n                    <jats:p>LUZP4\u2010IgG represents a novel serological biomarker of PNS and has high predictive value for germ cell tumors. The demonstrated antigen\u2010specific T\u2010cell responses support a CD8+\u2009T\u2010cell\u2013mediated cytotoxic paraneoplastic and antitumor potential. ANN NEUROL 2021;89:1001\u20131010<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/ana.26050","type":"journal-article","created":{"date-parts":[[2021,2,14]],"date-time":"2021-02-14T12:56:38Z","timestamp":1613307398000},"page":"1001-1010","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":62,"title":["Leucine Zipper 4 Autoantibody: A Novel Germ Cell Tumor and Paraneoplastic Biomarker"],"prefix":"10.1002","volume":"89","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4302-4075","authenticated-orcid":false,"given":"Divyanshu","family":"Dubey","sequence":"first","affiliation":[{"name":"Department of Neurology Mayo Clinic  Rochester NY"},{"name":"Department of Laboratory Medicine and Pathology Mayo Clinic  Rochester NY"},{"name":"Center for Multiple Sclerosis and Autoimmune Neurology Mayo Clinic  Rochester NY"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Kryzer","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine and Pathology Mayo Clinic  Rochester NY"},{"name":"Center for Multiple Sclerosis and Autoimmune Neurology Mayo Clinic  Rochester NY"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yong","family":"Guo","sequence":"additional","affiliation":[{"name":"Department of Neurology Mayo Clinic  Rochester NY"},{"name":"Center for Multiple Sclerosis and Autoimmune Neurology Mayo Clinic  Rochester NY"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2054-3486","authenticated-orcid":false,"given":"Benjamin","family":"Clarkson","sequence":"additional","affiliation":[{"name":"Department of Neurology Mayo Clinic  Rochester NY"},{"name":"Center for Multiple Sclerosis and Autoimmune Neurology Mayo Clinic  Rochester NY"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John C.","family":"Cheville","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine and Pathology Mayo Clinic  Rochester NY"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brian A.","family":"Costello","sequence":"additional","affiliation":[{"name":"Division of Medical Oncology Mayo Clinic  Rochester NY"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bradley C.","family":"Leibovich","sequence":"additional","affiliation":[{"name":"Department of Urology Mayo Clinic  Rochester NY"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alicia","family":"Algeciras\u2010Schimnich","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine and Pathology Mayo Clinic  Rochester NY"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claudia","family":"Lucchinnetti","sequence":"additional","affiliation":[{"name":"Department of Neurology Mayo Clinic  Rochester NY"},{"name":"Center for Multiple Sclerosis and Autoimmune Neurology Mayo Clinic  Rochester NY"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M. Bakri","family":"Hammami","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine and Pathology Mayo Clinic  Rochester NY"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew M.","family":"Knight","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine and Pathology Mayo Clinic  Rochester NY"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charles","family":"Howe","sequence":"additional","affiliation":[{"name":"Department of Neurology Mayo Clinic  Rochester NY"},{"name":"Center for Multiple Sclerosis and Autoimmune Neurology Mayo Clinic  Rochester NY"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vanda A.","family":"Lennon","sequence":"additional","affiliation":[{"name":"Department of Neurology Mayo Clinic  Rochester NY"},{"name":"Department of Laboratory Medicine and Pathology Mayo Clinic  Rochester NY"},{"name":"Center for Multiple Sclerosis and Autoimmune Neurology Mayo Clinic  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