Background/Purpose: Neuropsychiatric (NP) events are found in patients with rheumatic diseases, commonly in systemic lupus erythematosus (SLE) and Sjögren’s syndrome (SS). The standard nomenclature and case definitions for 19 NPSLE syndromes by the American College of Rheumatology (ACR) Committee on Research cover a wide range of NP events seen in both SLE and SS. Despite advances in the understanding of SLE and SS, NP syndromes continue to pose diagnostic challenges. Correct attribution of NP events is critical in determining the correct treatment and prognosis. Anti-N-methyl-_D-aspartate receptor subunits NR2A/B (anti-NR2A/B) antibodies (Abs) have been demonstrated in the sera of SLE and SS patients and have been associated with collective or specific NP syndromes, though not consistently. Interpretation of anti-NR2A/B Abs data in the medical literature is rendered difficult by small sample size of patient groups. By combining different studies to generate a pooled effect size, a meta-analysis can increase the power to detect differences in the presence or absence of NP syndromes. Hence, we set out to perform a meta-analysis to assess the association between anti-NR2A/B Abs and NP syndromes in SLE and SS.

Methods: A literature search was conducted using PubMed and other databases from inception to June 2016. We abstracted data relating to anti-NR2A/B Abs from the identified studies. Random-effects model was used to calculate overall combined odds ratio (OD) with its corresponding 95% confidence interval (CI) to evaluate the relationship between anti-NR2A/B Ab and NP syndromes in SLE and SS patients with and without NP events. We also included our own series of 57 SLE patients fulfilling the ACR 1997 revised classification criteria and 58 healthy controls (HCs).

Results: In total, 17 studies with data on anti-NR2A/B Abs in 2,212 SLE patients, 66 SS patients, 99 disease controls (DCs) (e.g. antiphospholipid syndrome, myasthenia gravis and autoimmune polyendocrine syndrome I) and 538 HCs were used in this analysis. Overall pooled prevalence of serum/plasma anti-NR2A/B Abs was higher in SLE patients [24.6% (95% CI 18.5-32.0%)] and SS patients [19.7% (95% CI 11.8-31.0%)] compared to DCs [14.8% (95% CI 2.2-56.9)] and HCs [7.6% (95% CI 4.6-12.4%)] (p = 0.001). There was a significantly greater proportion of SLE and SS patients with NP syndromes who demonstrated positivity for serum/plasma anti-NR2A/B Abs [pooled OR = 1.607 (95% CI 1.041-2.479), p = 0.032] as compared to SLE and SS patients without NP syndromes in 13 studies. Usable data for cerebrospinal fluid anti-NR2A/B Abs was available in only 4 studies [pooled OR = 0.831 (95% CI 0.365-1.888), p = 0.658]. Among the 19 NP syndromes, serum/plasma anti-NR2A/B Abs were not specifically associated with any NP syndrome, including cognitive dysfunction (p = 0.259) and mood disorder (p = 0.503). Meta-regression identified proportion of anti-double-stranded deoxyribonucleic acid Ab positivity (p = 0.009) and SLE Disease Activity Index (p = 0.028) as moderators for the heterogeneity of serum/plasma anti-NR2A/B Abs.

Conclusion: Circulating anti-NR2A/B Abs testing has a diagnostic value for NP syndromes in SLE and SS collectively, but it is not helpful in differentiating specific NP syndromes.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/clinical-utility-of-circulating-anti-n-methyl-d-aspartate-receptor-subunits-nr2ab-antibody-for-the-diagnosis-of-neuropsychiatric-syndromes-in-systemic-lupus-erythematosus-and-sjogrens-syndrome-an/