Relationship between serum NR2a antibodies and cognitive dysfunction in systemic lupus erythematosus

To assess the association between serum NR2a antibodies and cognitive dysfunction in systemic lupus erythematosus (SLE).

The study population consisted of English-speaking adults who met American College of Rheumatology (ACR) criteria for SLE and had at least 1 serum sample stored in the Hospital for Special Surgery Autoimmune Registry and Repository. Demographic and clinical information was obtained, and patients completed the neuropsychological test battery recommended by the ACR, the Center for Epidemiologic Studies Depression Scale, and the Spielberger State-Trait Anxiety Inventory. Cognitive impairment was defined as scores >1.5 SD below the mean of age-matched published normative data on at least 2 neuropsychological tests. Sera were tested for NR2a antibodies by enzyme-linked immunosorbent assay. Performance on neuropsychological tests was compared between NR2a-positive and NR2a-negative patients.

Of the 93 patients, 24 (25.8%) were positive for NR2a antibodies. Of the 48 patients who were cognitively impaired based on test results, 31% were positive for NR2a antibodies, compared with 20% of those who were not cognitively impaired (P = 0.24). Among antibody-positive patients, the mean +/- SD number of neuropsychological tests with abnormal results was 2.3 +/- 2.2, compared with 2.0 +/- 1.8 in the antibody-negative group (P = 0.59). Similar nonsignificant differences were found when impairment was defined using a more stringent definition (i.e., test scores >2.0 SD below the mean) and using a neuropsychologist's clinical ratings. No association was detected between NR2a antibody positivity and depressive symptoms (P = 0.73) or anxiety (P = 0.42).

No significant association was found between NR2a antibody positivity and cognitive dysfunction, depressive symptoms, or anxiety. These results indicate that the presence of these antibodies alone does not have a direct effect on cognitive functioning or any other neuropsychiatric manifestation of SLE.