{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n Cerebellar degeneration‐related protein 2‐like (CDR2L) has emerged as a key autoantigen in paraneoplastic cerebellar degeneration (PCD) associated with anti‐Yo antibodies. Studies of ovarian carcinomas from patients with Yo‐PCD have demonstrated that, along with CDR2, CDR2L frequently undergoes somatic mutations and gene copy gains that lead to tumor protein overexpression and protein deposits, suggesting that genetic alterations in CDR2L may trigger a breakdown in immune tolerance and precipitate the autoimmune response."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n In ovarian cancer tissue, CDR2L is widely expressed not only in tumors from patients with paraneoplastic neurological syndromes but also in normal tissues, supporting its role as a broadly distributed antigen. However, its clinical significance is especially pronounced in PCD, where it is recognized preferentially by Yo antibodies. Indeed, functional and diagnostic studies have demonstrated that Yo antibodies bind endogenous CDR2L (but not endogenous CDR2), making CDR2L the major antigen in these disorders."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n Subcellular localization studies reveal that CDR2L resides predominantly in the cytoplasm of Purkinje neurons, where it colocalizes with components of the ribosomal machinery (such as the 40S ribosomal protein S6). This finding suggests that the binding of Yo antibodies to CDR2L may directly interfere with protein synthesis, potentially disrupting neuronal function and contributing to neurodegeneration in PCD."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n Moreover, diagnostic assays that include cell‐based testing for CDR2L have shown improved specificity for detecting PCD, underlining the importance of CDR2L as a biomarker in the disease. In fact, only sera from patients with confirmed PCD react with CDR2L in such assays, and its cell membrane accessibility further supports a primary pathogenic role in mediating antibody‐induced neuronal injury."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "6", "end_ref": "8"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n In summary, CDR2L functions as the principal target of Yo antibodies in PCD. Its altered expression and genetic modifications in tumors, coupled with its strategic localization in neurons where it is involved in ribosomal interactions, render it a critical mediator of immune‐driven neurodegeneration and a promising diagnostic marker for PCD.\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Mathilde Small, Isabelle Treilleux, Coline Couillault, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Genetic alterations and tumor immune attack in Yo paraneoplastic cerebellar degeneration."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Acta Neuropathol (2018)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1007/s00401-017-1802-y"}], "href": "https://doi.org/10.1007/s00401-017-1802-y"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "29299667"}], "href": "https://pubmed.ncbi.nlm.nih.gov/29299667"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Clément Vialatte de Pémille, Giulia Berzero, Mathilde Small, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Transcriptomic immune profiling of ovarian cancers in paraneoplastic cerebellar degeneration associated with anti-Yo antibodies."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Br J Cancer (2018)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/s41416-018-0125-7"}], "href": "https://doi.org/10.1038/s41416-018-0125-7"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "29899393"}], "href": "https://pubmed.ncbi.nlm.nih.gov/29899393"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Margrethe Raspotnig, Mette Haugen, Maria Thorsteinsdottir, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Cerebellar degeneration-related proteins 2 and 2-like are present in ovarian cancer in patients with and without Yo antibodies."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cancer Immunol Immunother (2017)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1007/s00262-017-2041-8"}], "href": "https://doi.org/10.1007/s00262-017-2041-8"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "28710511"}], "href": "https://pubmed.ncbi.nlm.nih.gov/28710511"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Torbjørn Kråkenes, Ida Herdlevaer, Margrethe Raspotnig, et al. "}, {"type": "b", "children": [{"type": "t", "text": "CDR2L Is the Major Yo Antibody Target in Paraneoplastic Cerebellar Degeneration."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Ann Neurol (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/ana.25511"}], "href": "https://doi.org/10.1002/ana.25511"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "31148214"}], "href": "https://pubmed.ncbi.nlm.nih.gov/31148214"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Ida Herdlevaer, Torbjørn Kråkenes, Manja Schubert, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Localization of CDR2L and CDR2 in paraneoplastic cerebellar degeneration."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Ann Clin Transl Neurol (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/acn3.51212"}], "href": "https://doi.org/10.1002/acn3.51212"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "33009713"}], "href": "https://pubmed.ncbi.nlm.nih.gov/33009713"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Ida Herdlevær, Mette Haugen, Kibret Mazengia, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Paraneoplastic Cerebellar Degeneration: The Importance of Including CDR2L as a Diagnostic Marker."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Neurol Neuroimmunol Neuroinflamm (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1212/NXI.0000000000000963"}], "href": "https://doi.org/10.1212/NXI.0000000000000963"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "33531379"}], "href": "https://pubmed.ncbi.nlm.nih.gov/33531379"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Margrethe Raspotnig, Torbjørn Kråkenes, Ida Herdlevær, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Expression of cerebellar degeneration-related proteins CDR2 and CDR2L in human and rat brain tissue."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Neuroimmunol (2022)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.jneuroim.2021.577766"}], "href": "https://doi.org/10.1016/j.jneuroim.2021.577766"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "34823119"}], "href": "https://pubmed.ncbi.nlm.nih.gov/34823119"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Tilo W Eichler, Cecilie Totland, Mette Haugen, et al. "}, {"type": "b", "children": [{"type": "t", "text": "CDR2L Antibodies: A New Player in Paraneoplastic Cerebellar Degeneration."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "PLoS One (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1371/journal.pone.0066002"}], "href": "https://doi.org/10.1371/journal.pone.0066002"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23823982"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23823982"}]}]}]}