title: Antibodies to Delta/notch-like epidermal growth factor-related receptor in patients with anti-Tr, paraneoplastic cerebellar degeneration, and Hodgkin lymphoma.
abstract: OBJECTIVE
  The anti-Tr immune response is associated with paraneoplastic cerebellar degeneration and Hodgkin lymphoma (HL). One case series has reported that the Delta/notch-like epidermal growth factor-related receptor (DNER) is the actual target for anti-Tr antibodies, but this result has not been replicated.
  
  
  OBJECTIVE
  To describe a patient with anti-Tr and confirm that DNER is the autoantigen for a series of patients with anti-Tr.
  
  
  METHODS
  Observational study and analysis of biological samples for antibodies to DNER at the hospital of the University of Pennsylvania. We examined a cerebrospinal fluid sample from 1 patient with anti-Tr and serum and/or cerebrospinal fluid samples from 5 other patients with anti-Tr.
  
  
  METHODS
  Transfection of HEK293T and Hela cells to express DNER coupled to an enhanced green fluorescent protein tag using a plasmid previously used to detect human DNER antibodies.
  
  
  RESULTS
  A man in his 30s with paraneoplastic cerebellar degeneration and anti-Tr underwent treatment with corticosteroids and intravenous immunoglobulin, resulting in clinical improvement before chemotherapy. Despite close oncologic follow-up, a biopsy, positron emission tomography, and computed tomography, he was not diagnosed as having HL until 6 months after symptom onset. The cerebrospinal fluid sample from this patient reacted with cells transfected to express DNER, as did cerebrospinal fluid and/or serum samples from 5 other patients with paraneoplastic cerebellar degeneration, HL, and anti-Tr. Only 4 of the 5 serum samples reacted to permeabilized cells enough to be distinguished from background, but all 5 serum samples convincingly labeled live cells, which had considerably less background. All 6 control serum samples and 1 serum sample from a patient previously diagnosed as having anti-Tr (but without HL or cerebellitis) did not recognize DNER.
  
  
  CONCLUSIONS
  This case demonstrates the importance of testing for the anti-Tr immune response in patients with cerebellar degeneration. The strong association of anti-Tr with HL requires careful surveillance for this tumor. We also confirm that DNER is the target antigen of the anti-Tr immune response. Screening for DNER antibodies against living transfected cells may offer an improved signal-to-noise characteristic compared with immunostaining of fixed, permeabilized cells.
authors.affiliation: Department of Neurology, University of Pennsylvania School of Medicine, Philadelphia.
authors.forename: Maxwell
authors.initials: M
authors.lastname: Greene
authors.affiliation: Department of Neurology, University of Pennsylvania School of Medicine, Philadelphia.
authors.forename: Yongjie
authors.initials: Y
authors.lastname: Lai
authors.affiliation: currently an undergraduate at the University of Pennsylvania, Philadelphia.
authors.forename: Nicolle
authors.initials: N
authors.lastname: Baella
authors.affiliation: Department of Neurology, University of Pennsylvania School of Medicine, Philadelphia3Department of Neurology, Hospital Clinic, Institut d'Investigacions Biomèdiques August Pi i Sunyer, Barcelona, Spain4Department of Neurology, Institució Catalana de Recer.
authors.forename: Josep
authors.initials: J
authors.lastname: Dalmau
authors.affiliation: Department of Neurology, University of Pennsylvania School of Medicine, Philadelphia.
authors.forename: Eric
authors.initials: E
authors.lastname: Lancaster
mesh_terms: D000328:Adult; D001323:Autoantibodies / Q000097:blood / Q000134:cerebrospinal fluid; D002648:Child; D005260:Female; D006689:Hodgkin Disease / Q000175:diagnosis* / Q000276:immunology; D006801:Humans; D008297:Male; D008875:Middle Aged; D009419:Nerve Tissue Proteins / Q000276:immunology*; D020362:Paraneoplastic Cerebellar Degeneration / Q000175:diagnosis* / Q000276:immunology; D011956:Receptors, Cell Surface / Q000276:immunology*
chemical_list: D001323:Autoantibodies; C462501:DNER protein, human; D009419:Nerve Tissue Proteins; D011956:Receptors, Cell Surface