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Anti-NR2 Glutamate Receptor Antibodies and Cognitive Function in Systemic Lupus Erythematosus
JOHN G. HANLY, JODY ROBICHAUD, and JOHN D. FISK ABSTRACT. Objective. To determine the prevalence of circulating anti-NR2 antibodies and their association with neuropsychiatric systemic lupus erythematosus (NP-SLE), particularly cognitive function, in women with SLE. Methods. Cognitive function was assessed in 65 consecutive women with SLE from a single referral center using standardized neuropsychological tests. These were selected subtests of the Wechsler Adult Intelligence Scale-Revised, the Wechsler Memory Scale-Revised, and the California Verbal Learning Test, which provided information on 8 areas of cognitive function. After a mean followup of 64 (range 52–71) months, cognitive assessments were repeated. Global and domain-specific cognitive impairment was examined using predetermined decision rules, and the change in individual tests of cognitive performance over time was also examined. Overt NP-SLE was identified by clinical assessment and classified using the American College of Rheumatology nomenclature. Circulating IgG anti-NR2 and anti-dsDNA antibodies were determined by ELISA on up to 4 occasions over the study period. A positive result was defined as at least 3 standard deviations above the mean of healthy controls. Results. At enrollment, 15/65 (23%) patients had cognitive impairment. This fell to 7/54 (13%) at followup. In addition 15/65 (23%) patients had a history of clinically overt NP-SLE. Twenty-three of 65 (35%) patients had anti-NR2 antibodies and 48/65 (74%) had anti-dsDNA antibodies. Anti-NR2 antibodies were present in 18/48 (38%) patients with anti-DNA antibodies, and 18/23 patients (78%) with anti-NR2 antibodies also had anti-dsDNA antibodies. There was no association between global cognitive impairment, domain-specific cognitive impairment, or a history of clinically overt NP-SLE and either the presence or amount of anti-NR2 or anti-dsDNA antibodies (p > 0.05). When change in cognitive performance or the occurrence of new NP-SLE events over the 5-year followup period was examined, there was no significant association with persistent elevation of either antibody (p > 0.05). Similarly there was no association between a rise in autoantibodies over time and the development of overt NP events or cognitive decline (p > 0.05). Conclusion. These results indicate that anti-NR2 antibodies occur in 35% of women with SLE and are infrequent in the absence of detectable anti-dsDNA antibodies. Their presence in the circulation is not associated with cognitive dysfunction at a single timepoint, and an increase in or persistently elevated antibody levels are not associated with a change in cognitive performance over time. There was no association with clinically overt NP-SLE. However, as our study did not examine cerebrospinal fluid samples, these results do not exclude a potential pathogenic role in selected patients for this group of autoantibodies should they penetrate the blood-brain barrier and thereby gain direct access to neuronal tissues. (J Rheumatol 2006;33:1553–8) Key Indexing Terms:
GLUTAMATE RECEPTOR ANTIBODIES From the Division of Rheumatology, Department of Medicine, and the Department of Psychiatry, Dalhousie University, Halifax, Nova Scotia, Canada. Supported by a grant from the Canadian Institutes of Health Research. J.G. Hanly, MD, MRCPI, FRCPC, Professor of Medicine; J. Robichaud, BSc, Research Technologist, Division of Rheumatology, Department of Medicine; J.D. Fisk, PhD, Associate Professor of Psychiatry, Department of Psychiatry, Dalhousie University. Address reprint requests to Dr. J.G. Hanly, Division of Rheumatology, Nova Scotia Rehabilitation Center, 2nd Floor, 1341 Summer Street, Halifax, Nova Scotia B3H 4K4, Canada. E-mail: john.hanly@cdha.nshealth.ca Accepted for publication March 2, 2006.
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