Clinical significance of the determination of antibodies to the NR2 subunit of glutamate N-methyl-D-aspartate receptors (aNMDAR) in patients with systemic lupus erythematosus and antiphospholipid syndrome

The aim – to determine the clinical significance of hyperproduction of antibodies to the NR2 subunit of glutamate N-methyl-D-aspartate receptors (aNMDAR) in patients with systemic lupus erythematosus (SLE) and antiphospholipid syndrome (APS).

Material and methods. The study included 66 patients with reliable diagnoses of SLE and APS (SLE – 24 patients; SLE+APS – 18 patients, primary APS – 24 patients). Young women (35.5±10.2 years) prevailed (72.7%). All patients were examined according to the standards recommended by the Association of Rheumatologists of Russia, and also examined by a psychiatrist. Neuropsychiatric syndromes, mainly psychiatric, were detected in 62 (93.9%) patients. aNMDAR was determined in all patients and 20 healthy donors, matched by gender and age, by enzyme immunoassay in blood serum.

Results. The concentration of aNMDAR in patients with neurological manifestations of SLE and APS did not exceed the threshold value, but was significantly higher than in healthy donors (4.32±2.0 versus 2.96±1.44 ng/ml, respectively; p=0.042). Patients with elevated aNMDAR concentrations had a statistically significantly higher (p<0.05) probability of detecting neurological manifestations such as acute/transient cerebrovascular accident/epilepsy (odds ratio (OR) – 9.0), as well as bipolar affective disorder (OR=14.0), and statistically not significantly – schizotypal disorder (OR=3.8) and moderate cognitive impairment (organic type) (OR=2.15). The probability of detecting APS in patients with elevated aNMDAR values was 1.7 times higher, the risk of thrombosis according to the GAPSS (Global Anti-Phospholipid Syndrome Score) was 4.28 times higher, and aPL positivity (aCL, aß2GP-1, aFs/Pt) and a-ds-DNA – 2.5–6.73 times (the differences were not statistically significant).

Conclusion. aNMDAR may play an important role in the development of certain neuropsychiatric manifestations in patients with SLE and APS. It is advisable to conduct larger-scale studies aimed at confirming the need to identify aNMDAR as a biomarker for the diagnosis and monitoring of the progression of neuropsychiatric manifestations of SLE and APS.

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