Paraneoplastic cerebellar degeneration associated with an onconeural antibody against creatine kinase, brain-type

• Published in: Journal of the neurological sciences Vol. 335; no. 1; pp. 48 - 57
• Main Authors: Tetsuka, Syuichi, Tominaga, Kaoru, Ohta, Eriko, Kuroiwa, Kenji, Sakashita, Eiji, Kasashima, Katsumi, Hamamoto, Toshiro, Namekawa, Michito, Morita, Mitsuya, Natsui, Shinsuke, Morita, Tatsuo, Tanaka, Keiko, Takiyama, Yoshihisa, Nakano, Imaharu, Endo, Hitoshi
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 15.12.2013
• Subjects: Aged; Antibodies - metabolism; Brain - metabolism; Brain - pathology; Cancer; Creatine Kinase - immunology; Creatine kinase, brain-type; Electrophoresis, Gel, Two-Dimensional; Enzyme-Linked Immunosorbent Assay; Humans; Male; Mass Spectrometry; Nerve Tissue Proteins - metabolism; Neurology; Onconeural antibody; Paraneoplastic cerebellar degeneration; Paraneoplastic Cerebellar Degeneration - blood; Paraneoplastic Cerebellar Degeneration - cerebrospinal fluid; Paraneoplastic Cerebellar Degeneration - immunology; Paraneoplastic Cerebellar Degeneration - pathology; Paraneoplastic neurological syndromes; Proteomics; Onconeural antibody; Paraneoplastic neurological syndromes; Creatine kinase, brain-type; Paraneoplastic cerebellar degeneration; Proteomics; Cancer
• ISSN: 0022-510X; 1878-5883
• DOI: 10.1016/j.jns.2013.08.022

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.