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March 2021; 8 (2) ArticleOpen Access

Paraneoplastic Cerebellar Degeneration

The Importance of Including CDR2L as a Diagnostic Marker

View ORCID ProfileIda Herdlevær, Mette Haugen, Kibret Mazengia, Cecilie Totland, View ORCID ProfileChristian Vedeler
First published February 2, 2021, DOI: https://doi.org/10.1212/NXI.0000000000000963
Ida Herdlevær
From the Department of Neurology (I.H., M.H., C.T., C.V.), Haukeland University Hospital; Department of Clinical Medicine (I.H., K.M., C.V.), University of Bergen; and Departments of Neurology and Clinical Medicine (I.H., C.T., C.V.), Neuro-SysMed—Centre of Excellence for Experimental Therapy in Neurology, Bergen, Norway.
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Mette Haugen
From the Department of Neurology (I.H., M.H., C.T., C.V.), Haukeland University Hospital; Department of Clinical Medicine (I.H., K.M., C.V.), University of Bergen; and Departments of Neurology and Clinical Medicine (I.H., C.T., C.V.), Neuro-SysMed—Centre of Excellence for Experimental Therapy in Neurology, Bergen, Norway.
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Kibret Mazengia
From the Department of Neurology (I.H., M.H., C.T., C.V.), Haukeland University Hospital; Department of Clinical Medicine (I.H., K.M., C.V.), University of Bergen; and Departments of Neurology and Clinical Medicine (I.H., C.T., C.V.), Neuro-SysMed—Centre of Excellence for Experimental Therapy in Neurology, Bergen, Norway.
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Cecilie Totland
From the Department of Neurology (I.H., M.H., C.T., C.V.), Haukeland University Hospital; Department of Clinical Medicine (I.H., K.M., C.V.), University of Bergen; and Departments of Neurology and Clinical Medicine (I.H., C.T., C.V.), Neuro-SysMed—Centre of Excellence for Experimental Therapy in Neurology, Bergen, Norway.
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Christian Vedeler
From the Department of Neurology (I.H., M.H., C.T., C.V.), Haukeland University Hospital; Department of Clinical Medicine (I.H., K.M., C.V.), University of Bergen; and Departments of Neurology and Clinical Medicine (I.H., C.T., C.V.), Neuro-SysMed—Centre of Excellence for Experimental Therapy in Neurology, Bergen, Norway.
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Citation
Paraneoplastic Cerebellar Degeneration
The Importance of Including CDR2L as a Diagnostic Marker
Ida Herdlevær, Mette Haugen, Kibret Mazengia, Cecilie Totland, Christian Vedeler
Neurol Neuroimmunol Neuroinflamm Mar 2021, 8 (2) e963; DOI: 10.1212/NXI.0000000000000963

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    Figure 1 Representative Images of Rat Cerebellar Sections Incubated With Patient Samples

    (A) Sera from confirmed paraneoplastic cerebellar degeneration (PCD) cases (cerebellar degeneration-related protein 2-like [CDR2L]+/cerebellar degeneration-related protein 2 [CDR2]+, patients 1–6) show granular, cytoplasmic staining of Purkinje neurons. (B) Sera from the 2 cases without PCD but with previously detected cancer (CDR2L−/CDR2+, patients 7 and 8) stain the cytoplasm of Purkinje neurons, but no granular staining is observed. (C) Sera from the remaining cases without PCD and without cancer (CDR2L−/CDR2+, patient 9–13) do not stain Purkinje neurons of rat cerebellar sections. CDR2L/CDR2 testing is based on line blots and cell-based assays. G = granular layer; M = molecular layer; P = Purkinje neuron layer. Scale bar = 20 μm; zoom in scale bar = 10 μm.

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    Figure 2 No Cross-Reactivity Is Observed Between CDR2 Antibodies and CDR2L in Human Embryonic Kidney 293 Cells That Express Myc-DDK-Tagged CDR2L

    Upper row: cells stained with anti-CDR2L (green) and anti-DDK (red). Lower row: cells stained with anti-CDR2 (no reaction), and anti-DDK (red). Nuclei are stained with DAPI. Scale bar = 20 μm. CDR2 = cerebellar degeneration-related protein 2; CDR2L = cerebellar degeneration-related protein 2-like.

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    Figure 3 Representative Images of Patient Sera (1:100) Double Positive for CDR2L and CDR2 (A.a–A.c), and Single Positive for CDR2 (B.a–B.c) in Indirect Immunofluorescence of CDR2L Transfected Human Embryonic Kidney 293 Cells (A.a, B.a), Commercial CBA for CDR2 (A.b, B.b), and WB (A.c, B.c)

    A negative control containing reticulocyte lysate without recombinant protein was included in each experiment. Anti-CDR2/CDR2L, green; anti-DDK, red; merge, yellow. Scale bar = 20 μm. CBA = cell-based assay; CDR2 = cerebellar degeneration-related protein 2; CDR2L = cerebellar degeneration-related protein 2-like; WB = Western blot analysis.

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