title: DPPX potassium channel antibody: frequency, clinical accompaniments, and outcomes in 20 patients.
abstract: OBJECTIVE
  To describe the detection frequency and clinical associations of immunoglobulin G (IgG) targeting dipeptidyl-peptidase-like protein-6 (DPPX), a regulatory subunit of neuronal Kv4.2 potassium channels.
  
  
  METHODS
  Specimens from 20 patients evaluated on a service basis by tissue-based immunofluorescence yielded a synaptic immunostaining pattern consistent with DPPX-IgG (serum, 20; CSF, all 7 available). Transfected HEK293 cell-based assay confirmed DPPX specificity in all specimens. Sixty-nine patients with stiff-person syndrome and related disorders were also evaluated by DPPX-IgG cell-based assay.
  
  
  RESULTS
  Of 20 seropositive patients, 12 were men; median symptom onset age was 53 years (range, 13-75). Symptom onset was insidious in 15 and subacute in 5. Twelve patients reported prodromal weight loss. Neurologic disorders were multifocal. All had one or more brain or brainstem manifestations: amnesia (16), delirium (8), psychosis (4), depression (4), seizures (2), and brainstem disorders (15; eye movement disturbances [8], ataxia [7], dysphagia [6], dysarthria [4], respiratory failure [3]). Nine patients reported sleep disturbance. Manifestations of central hyperexcitability included myoclonus (8), exaggerated startle (6), diffuse rigidity (6), and hyperreflexia (6). Dysautonomia involved the gastrointestinal tract (9; diarrhea [6], gastroparesis, and constipation [3]), bladder (7), cardiac conduction system (3), and thermoregulation (1). Two patients had B-cell neoplasms: gastrointestinal lymphoma (1), and chronic lymphocytic leukemia (1). Substantial neurologic improvements followed immunotherapy in 7 of 11 patients with available treatment data. DPPX-IgG was not detected in any of the stiff-person syndrome patients.
  
  
  CONCLUSIONS
  DPPX-IgG is a biomarker for an immunotherapy-responsive multifocal neurologic disorder of the central and autonomic nervous systems.
authors.affiliation: From the Departments of Neurology (W.O.T., V.A.L., S.L.C., A.J.A., C.F.L., J.Y.M., S.J.P., P.S., M.T.-P., E.C.W., A.M.), Laboratory Medicine and Pathology (V.A.L., S.J.P., A.M.), Immunology (V.A.L.), and Pediatrics (E.C.W.), College of Medicine, Mayo Clinic, Rochester, MN; Euroimmun AG (L.K., C.P.), Lübeck, Germany; and Neurology (J.P.A.), Faculty of Medicine, University of Manitoba, Canada.
authors.forename: William Oliver
authors.initials: WO
authors.lastname: Tobin
authors.affiliation: From the Departments of Neurology (W.O.T., V.A.L., S.L.C., A.J.A., C.F.L., J.Y.M., S.J.P., P.S., M.T.-P., E.C.W., A.M.), Laboratory Medicine and Pathology (V.A.L., S.J.P., A.M.), Immunology (V.A.L.), and Pediatrics (E.C.W.), College of Medicine, Mayo Clinic, Rochester, MN; Euroimmun AG (L.K., C.P.), Lübeck, Germany; and Neurology (J.P.A.), Faculty of Medicine, University of Manitoba, Canada.
authors.forename: Vanda A
authors.initials: VA
authors.lastname: Lennon
authors.affiliation: From the Departments of Neurology (W.O.T., V.A.L., S.L.C., A.J.A., C.F.L., J.Y.M., S.J.P., P.S., M.T.-P., E.C.W., A.M.), Laboratory Medicine and Pathology (V.A.L., S.J.P., A.M.), Immunology (V.A.L.), and Pediatrics (E.C.W.), College of Medicine, Mayo Clinic, Rochester, MN; Euroimmun AG (L.K., C.P.), Lübeck, Germany; and Neurology (J.P.A.), Faculty of Medicine, University of Manitoba, Canada.
authors.forename: Lars
authors.initials: L
authors.lastname: Komorowski
authors.affiliation: From the Departments of Neurology (W.O.T., V.A.L., S.L.C., A.J.A., C.F.L., J.Y.M., S.J.P., P.S., M.T.-P., E.C.W., A.M.), Laboratory Medicine and Pathology (V.A.L., S.J.P., A.M.), Immunology (V.A.L.), and Pediatrics (E.C.W.), College of Medicine, Mayo Clinic, Rochester, MN; Euroimmun AG (L.K., C.P.), Lübeck, Germany; and Neurology (J.P.A.), Faculty of Medicine, University of Manitoba, Canada.
authors.forename: Christian
authors.initials: C
authors.lastname: Probst
authors.affiliation: From the Departments of Neurology (W.O.T., V.A.L., S.L.C., A.J.A., C.F.L., J.Y.M., S.J.P., P.S., M.T.-P., E.C.W., A.M.), Laboratory Medicine and Pathology (V.A.L., S.J.P., A.M.), Immunology (V.A.L.), and Pediatrics (E.C.W.), College of Medicine, Mayo Clinic, Rochester, MN; Euroimmun AG (L.K., C.P.), Lübeck, Germany; and Neurology (J.P.A.), Faculty of Medicine, University of Manitoba, Canada.
authors.forename: Stacey Lynn
authors.initials: SL
authors.lastname: Clardy
authors.affiliation: From the Departments of Neurology (W.O.T., V.A.L., S.L.C., A.J.A., C.F.L., J.Y.M., S.J.P., P.S., M.T.-P., E.C.W., A.M.), Laboratory Medicine and Pathology (V.A.L., S.J.P., A.M.), Immunology (V.A.L.), and Pediatrics (E.C.W.), College of Medicine, Mayo Clinic, Rochester, MN; Euroimmun AG (L.K., C.P.), Lübeck, Germany; and Neurology (J.P.A.), Faculty of Medicine, University of Manitoba, Canada.
authors.forename: Allen J
authors.initials: AJ
authors.lastname: Aksamit
authors.affiliation: From the Departments of Neurology (W.O.T., V.A.L., S.L.C., A.J.A., C.F.L., J.Y.M., S.J.P., P.S., M.T.-P., E.C.W., A.M.), Laboratory Medicine and Pathology (V.A.L., S.J.P., A.M.), Immunology (V.A.L.), and Pediatrics (E.C.W.), College of Medicine, Mayo Clinic, Rochester, MN; Euroimmun AG (L.K., C.P.), Lübeck, Germany; and Neurology (J.P.A.), Faculty of Medicine, University of Manitoba, Canada.
authors.forename: Juan Pablo
authors.initials: JP
authors.lastname: Appendino
authors.affiliation: From the Departments of Neurology (W.O.T., V.A.L., S.L.C., A.J.A., C.F.L., J.Y.M., S.J.P., P.S., M.T.-P., E.C.W., A.M.), Laboratory Medicine and Pathology (V.A.L., S.J.P., A.M.), Immunology (V.A.L.), and Pediatrics (E.C.W.), College of Medicine, Mayo Clinic, Rochester, MN; Euroimmun AG (L.K., C.P.), Lübeck, Germany; and Neurology (J.P.A.), Faculty of Medicine, University of Manitoba, Canada.
authors.forename: Claudia F
authors.initials: CF
authors.lastname: Lucchinetti
authors.affiliation: From the Departments of Neurology (W.O.T., V.A.L., S.L.C., A.J.A., C.F.L., J.Y.M., S.J.P., P.S., M.T.-P., E.C.W., A.M.), Laboratory Medicine and Pathology (V.A.L., S.J.P., A.M.), Immunology (V.A.L.), and Pediatrics (E.C.W.), College of Medicine, Mayo Clinic, Rochester, MN; Euroimmun AG (L.K., C.P.), Lübeck, Germany; and Neurology (J.P.A.), Faculty of Medicine, University of Manitoba, Canada.
authors.forename: Joseph Y
authors.initials: JY
authors.lastname: Matsumoto
authors.affiliation: From the Departments of Neurology (W.O.T., V.A.L., S.L.C., A.J.A., C.F.L., J.Y.M., S.J.P., P.S., M.T.-P., E.C.W., A.M.), Laboratory Medicine and Pathology (V.A.L., S.J.P., A.M.), Immunology (V.A.L.), and Pediatrics (E.C.W.), College of Medicine, Mayo Clinic, Rochester, MN; Euroimmun AG (L.K., C.P.), Lübeck, Germany; and Neurology (J.P.A.), Faculty of Medicine, University of Manitoba, Canada.
authors.forename: Sean J
authors.initials: SJ
authors.lastname: Pittock
authors.affiliation: From the Departments of Neurology (W.O.T., V.A.L., S.L.C., A.J.A., C.F.L., J.Y.M., S.J.P., P.S., M.T.-P., E.C.W., A.M.), Laboratory Medicine and Pathology (V.A.L., S.J.P., A.M.), Immunology (V.A.L.), and Pediatrics (E.C.W.), College of Medicine, Mayo Clinic, Rochester, MN; Euroimmun AG (L.K., C.P.), Lübeck, Germany; and Neurology (J.P.A.), Faculty of Medicine, University of Manitoba, Canada.
authors.forename: Paola
authors.initials: P
authors.lastname: Sandroni
authors.affiliation: From the Departments of Neurology (W.O.T., V.A.L., S.L.C., A.J.A., C.F.L., J.Y.M., S.J.P., P.S., M.T.-P., E.C.W., A.M.), Laboratory Medicine and Pathology (V.A.L., S.J.P., A.M.), Immunology (V.A.L.), and Pediatrics (E.C.W.), College of Medicine, Mayo Clinic, Rochester, MN; Euroimmun AG (L.K., C.P.), Lübeck, Germany; and Neurology (J.P.A.), Faculty of Medicine, University of Manitoba, Canada.
authors.forename: Maja
authors.initials: M
authors.lastname: Tippmann-Peikert
authors.affiliation: From the Departments of Neurology (W.O.T., V.A.L., S.L.C., A.J.A., C.F.L., J.Y.M., S.J.P., P.S., M.T.-P., E.C.W., A.M.), Laboratory Medicine and Pathology (V.A.L., S.J.P., A.M.), Immunology (V.A.L.), and Pediatrics (E.C.W.), College of Medicine, Mayo Clinic, Rochester, MN; Euroimmun AG (L.K., C.P.), Lübeck, Germany; and Neurology (J.P.A.), Faculty of Medicine, University of Manitoba, Canada.
authors.forename: Elaine C
authors.initials: EC
authors.lastname: Wirrell
authors.affiliation: From the Departments of Neurology (W.O.T., V.A.L., S.L.C., A.J.A., C.F.L., J.Y.M., S.J.P., P.S., M.T.-P., E.C.W., A.M.), Laboratory Medicine and Pathology (V.A.L., S.J.P., A.M.), Immunology (V.A.L.), and Pediatrics (E.C.W.), College of Medicine, Mayo Clinic, Rochester, MN; Euroimmun AG (L.K., C.P.), Lübeck, Germany; and Neurology (J.P.A.), Faculty of Medicine, University of Manitoba, Canada. mckeon.andrew@mayo.edu.
authors.forename: Andrew
authors.initials: A
authors.lastname: McKeon
mesh_terms: D000293:Adolescent; D000305:Adrenal Cortex Hormones / Q000627:therapeutic use; D000328:Adult; D000368:Aged; D001341:Autonomic Nervous System / Q000473:pathology; D001921:Brain / Q000473:pathology; D004152:Dipeptidyl-Peptidases and Tripeptidyl-Peptidases / Q000276:immunology*; D005260:Female; D005767:Gastrointestinal Diseases / Q000209:etiology; D057809:HEK293 Cells; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood* / Q000134:cerebrospinal fluid*; D007167:Immunotherapy; D008279:Magnetic Resonance Imaging; D008297:Male; D001523:Mental Disorders / Q000209:etiology; D008875:Middle Aged; D009419:Nerve Tissue Proteins / Q000276:immunology*; D009422:Nervous System Diseases / Q000175:diagnosis* / Q000378:metabolism / Q000503:physiopathology* / Q000628:therapy; D015221:Potassium Channels / Q000276:immunology*; D012893:Sleep Wake Disorders / Q000209:etiology; D014162:Transfection; D015431:Weight Loss / Q000502:physiology; D055815:Young Adult
chemical_list: D000305:Adrenal Cortex Hormones; D007074:Immunoglobulin G; D009419:Nerve Tissue Proteins; D015221:Potassium Channels; C503535:DPP6 protein, human; D004152:Dipeptidyl-Peptidases and Tripeptidyl-Peptidases