title: Paraneoplastic cerebellar degeneration associated with an onconeural antibody against creatine kinase, brain-type.
abstract: Onconeural immunity, a cancer-stimulated immune reaction that cross-reacts with neural tissues, is considered to be the principal pathological mechanism for paraneoplastic neurological syndromes (PNS). A common PNS is paraneoplastic cerebellar degeneration (PCD). We had encountered a PCD patient with urothelial carcinomas (UC) of the urinary bladder who was negative for the well-characterized PNS-related onconeural antibodies. In the present study, we aimed to identify a new PCD-related onconeural antibody, capable of recognizing both cerebellar neurons and cancer tissues from the patient, and applied a proteomic approach using mass spectrometry. We identified anti-creatine kinase, brain-type (CKB) antibody as a new autoantibody in the serum and cerebrospinal fluid from the patient. Immunohistochemistry indicated that anti-CKB antibody reacted with both cerebellar neurons and UC of the urinary bladder tissues. However, anti-CKB antibody was not detected in sera from over 30 donors, including bladder cancer patients without PCD, indicating that anti-CKB antibody is required for onset of PCD. We also detected anti-CKB antibody in sera from three other PCD patients. Our study demonstrated that anti-CKB antibody may be added to the list of PCD-related autoantibodies and may be useful for diagnosis of PCD.
authors.affiliation: Division of Neurology, Department of Internal Medicine, Jichi Medical University, 3311-1 Yakushiji, Shimotsuke, Tochigi 329-0498 Japan; Department of Biochemistry, Jichi Medical University, 3311-1 Yakushiji, Shimotsuke, Tochigi 329-0498 Japan.
authors.forename: Syuichi
authors.initials: S
authors.lastname: Tetsuka
authors.forename: Kaoru
authors.initials: K
authors.lastname: Tominaga
authors.forename: Eriko
authors.initials: E
authors.lastname: Ohta
authors.forename: Kenji
authors.initials: K
authors.lastname: Kuroiwa
authors.forename: Eiji
authors.initials: E
authors.lastname: Sakashita
authors.forename: Katsumi
authors.initials: K
authors.lastname: Kasashima
authors.forename: Toshiro
authors.initials: T
authors.lastname: Hamamoto
authors.forename: Michito
authors.initials: M
authors.lastname: Namekawa
authors.forename: Mitsuya
authors.initials: M
authors.lastname: Morita
authors.forename: Shinsuke
authors.initials: S
authors.lastname: Natsui
authors.forename: Tatsuo
authors.initials: T
authors.lastname: Morita
authors.forename: Keiko
authors.initials: K
authors.lastname: Tanaka
authors.forename: Yoshihisa
authors.initials: Y
authors.lastname: Takiyama
authors.forename: Imaharu
authors.initials: I
authors.lastname: Nakano
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Endo
mesh_terms: D000368:Aged; D000906:Antibodies / Q000378:metabolism*; D001921:Brain / Q000378:metabolism* / Q000473:pathology; D003402:Creatine Kinase / Q000276:immunology*; D015180:Electrophoresis, Gel, Two-Dimensional; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D008297:Male; D013058:Mass Spectrometry; D009419:Nerve Tissue Proteins / Q000378:metabolism; D020362:Paraneoplastic Cerebellar Degeneration / Q000097:blood / Q000134:cerebrospinal fluid / Q000276:immunology / Q000473:pathology*
chemical_list: D000906:Antibodies; D009419:Nerve Tissue Proteins; D003402:Creatine Kinase
keywords: Cancer; Creatine kinase, brain-type; Onconeural antibody; Paraneoplastic cerebellar degeneration; Paraneoplastic neurological syndromes; Proteomics