Anti-NR2 glutamate receptor antibodies and cognitive function in systemic lupus erythematosus.
Bibliographic record
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.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one teacher head, not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".