HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Figures Only Full Text Full Text (PDF) Correspondence: Submit a response Correspondence: View responses Alert me when this article is cited Alert me when Correspondence are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Bataller, L. Articles by Dalmau, J. Search for Related Content PubMed PubMed Citation Articles by Bataller, L. Articles by Dalmau, J. Related Collections All Immunology Autoimmune diseases All Oncology Paraneoplastic syndrome

Antibodies to Zic4 in paraneoplastic neurologic disorders and small-cell lung cancer

From the Department of Neurology (Dr. Bataller), Hospital Universitario La Fe, Valencia, Spain; the Departments of Microbiology and Immunology (Dr. Wade) and Neurology (H.D. Stacey), University of Arkansas for Medical Sciences, Little Rock; the Service of Neurology and Institut d’Investigacions Biomèdiques August Pí i Sunyer (IDIBAPS) (Dr. Graus), Hospital Clínic, University of Barcelona, Spain; and Department of Neurology (Drs. Rosenfeld and Dalmau), University of Pennsylvania, Philadelphia.

Address correspondence and reprint requests to Dr. Josep Dalmau, Department of Neurology, 3 W. Gates, University of Pennsylvania, 3400 Spruce Street, Philadelphia, PA 19104; e-mail: jdalmau{at}mail.med.upenn.edu

Objective: To determine whether serum Zic4 antibodies associate with paraneoplastic neurologic disorders (PND) and small-cell lung cancer (SCLC), and the association of these antibodies with other onconeuronal immunities associated with SCLC.

Design/Methods: The authors studied 498 patients (215 with PND and 283 without PND or without cancer). The presence of antibodies was tested with immunoblots of Zic4, HuD, and CRMP5 proteins. The tumor expression of these proteins was determined by immunohistochemistry.

Results: Zic4 antibodies were identified in 61 patients. Ninety-two percent of patients with Zic4 antibodies had SCLC; detection of these antibodies segregated with the presence of PND (p = 0.031). Intrathecal synthesis of Zic4 antibodies was demonstrated in 5/7 patients with PND. None of 175 control patients without PND or cancer had Zic4 antibodies. Because of the robust association between Zic autoimmunity and SCLC, all patients were tested for other SCLC-related antibodies; concurrent Zic4, Hu, or CRMP5 antibodies occurred in the serum or CSF of 27% of SCLC patients with PND. Patients with isolated Zic4 antibodies were more likely to develop predominant cerebellar dysfunction than patients with several immunities (p < 0.001). Tumors of patients with and without onconeuronal antibodies coexpressed Zic, Hu, and CRMP5 proteins, indicating that the tumor expression of these antigens is necessary, but not sufficient, for immunologic activation.

Conclusions: In patients with neurologic symptoms of unknown cause detection of Zic4 antibodies predicts a neoplasm, usually a SCLC, and suggests that the neurologic disorder is paraneoplastic. Detection of Zic4 antibodies often associates with anti-Hu or CRMP5 antibodies. Patients with isolated Zic4 antibodies are more likely to develop cerebellar dysfunction than those with concurrent immunities.

Received July 3, 2003. Accepted in final form November 10, 2003.

Presented in part at the 127th annual meeting of the American Neurological Association; New York, NY; October 2002.

This article has been cited by other articles:

				J. W. de Beukelaar and P. A. S. Smitt Managing paraneoplastic neurological disorders. Oncologist, March 1, 2006; 11(3): 292 - 305. [Abstract] [Full Text] [PDF]

				J. H. Jaster and J. Dalmau Antibodies to Zic4 in paraneoplastic neurologic disorders and small-cell lung cancer Neurology, October 12, 2004; 63(7): 1339 - 1339. [Full Text] [PDF]

Correspondence: