DPPX potassium channel antibody: frequency, clinical accompaniments, and outcomes in 20 patients

• Published in: Neurology Vol. 83; no. 20; p. 1797
• Main Authors: Tobin, William Oliver, Lennon, Vanda A, Komorowski, Lars, Probst, Christian, Clardy, Stacey Lynn, Aksamit, Allen J, Appendino, Juan Pablo, Lucchinetti, Claudia F, Matsumoto, Joseph Y, Pittock, Sean J, Sandroni, Paola, Tippmann-Peikert, Maja, Wirrell, Elaine C, McKeon, Andrew
• Format: Journal Article
• Language: English
• Published: United States 11.11.2014
• Subjects: Adolescent; Adrenal Cortex Hormones - therapeutic use; Adult; Aged; Autonomic Nervous System - pathology; Brain - pathology; Dipeptidyl-Peptidases and Tripeptidyl-Peptidases - immunology; Female; Gastrointestinal Diseases - etiology; HEK293 Cells; Humans; Immunoglobulin G - blood; Immunoglobulin G - cerebrospinal fluid; Immunotherapy; Magnetic Resonance Imaging; Male; Mental Disorders - etiology; Middle Aged; Nerve Tissue Proteins - immunology; Nervous System Diseases - diagnosis; Nervous System Diseases - metabolism; Nervous System Diseases - physiopathology; Nervous System Diseases - therapy; Potassium Channels - immunology; Sleep Wake Disorders - etiology; Transfection; Weight Loss - physiology; Young Adult
• ISSN: 1526-632X
• DOI: 10.1212/WNL.0000000000000991

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. 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. 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. DPPX-IgG is a biomarker for an immunotherapy-responsive multifocal neurologic disorder of the central and autonomic nervous systems.