BR serine/threonine kinase 2: a new autoantigen in paraneoplastic limbic encephalitis.
We describe a new antigen, BR serine/threonine kinase 2 (BRSK2), identified by an antibody present in the serum of a patient with limbic encephalitis and small-cell lung cancer (SCLC). Patient's serum immunolabeled the neuronal cytoplasm and, less intense, the neuropil of rat brain but did not immunoreact with other rat tissues with the exception of testis. Immunoblots of rat brain homogenate identified several immunoreactive bands in the range of 88-82 kDa and a weaker broad band of 47-43 kDa. Probing a rat hippocampus expression library with the patient's serum resulted in the isolation of BR serine/threonine kinase 2 (BRSK2), a protein (also know as SAD1B kinase) preferentially expressed in the brain and testis and implicated in neuronal polarization as well as synaptic development. Eluted IgG from the BRSK2 clone gave a similar immunolabeling than the patient's serum by immunohistochemistry and immunoblot of rat brain and testis. BRSK2 antibodies reacted with two SCLC from patients without paraneoplastic neurological syndromes. No anti-BRSK2 antibodies were found in the serum of 50 patients with SCLC without PNS, 19 with limbic encephalitis without onconeural antibodies, 50 with anti-Hu antibodies and several paraneoplastic neurological syndromes, including 14 with limbic encephalitis, and 160 with a variety of non-paraneoplastic neurological syndromes. Our study suggests BRSK2 may be an autoantigen involved in the pathogenesis of SCLC-associated limbic encephalitis.
Sabater
Lidia
L
Service of Neurology, Hospital Clinic, Universitat de Barcelona and Institut d' Investigació Biomèdica August Pi i Sunyer (IDIBAPS), Barcelona, Spain.
Gómez-Choco
Manuel
M
Saiz
Albert
A
Graus
Francesc
F
D000915:Antibody Affinity; D001323:Autoantibodies / Q000097:blood / Q000276:immunology; D001324:Autoantigens / Q000097:blood* / Q000235:genetics; D015153:Blotting, Western; D018288:Carcinoma, Small Cell / Q000150:complications*; D016384:Consensus Sequence; D051959:ELAV Proteins / Q000097:blood* / Q000235:genetics; D006801:Humans; D008032:Limbic System; D008175:Lung Neoplasms / Q000150:complications*; D008297:Male; D008875:Middle Aged; D020361:Paraneoplastic Syndromes, Nervous System / Q000209:etiology / Q000276:immunology*; D017346:Protein Serine-Threonine Kinases / Q000097:blood* / Q000235:genetics
D001323:Autoantibodies; D001324:Autoantigens; D051959:ELAV Proteins; C507732:Brsk2 protein, human; D017346:Protein Serine-Threonine Kinases