Background/Purpose: Neuropsychiatric manifestation in systemic lupus erythematosus (NPSLE) is one of the most serious complications of the disease. We have recently demonstrated that the breakdown of blood brain barrier (BBB) plays a crucial role in the development of diffuse psychiatric/neuropsychological manifestations (diffuse NPSLE), allowing influx of neuron-reactive autoantibodies from systemic circulation into the brain. However, the mechanism of BBB damages remains unclear. Of note, various autoantibodies have been implicated in the pathogenesis in NPSLE. The present study was designed in order to elucidate the roles of serum autoantibodies in the development of BBB damages In NPSLE.

Methods: Paired serum and cerebrospinal fluid (CSF) samples were obtained from 101 SLE patients when they presented active neuropsychiatric manifestations (69 patients with diffuse psychiatric/neuropsychological syndromes [diffuse NPSLE] and 32 patients with neurologic syndromes or peripheral nervous system involvement [focal NPSLE]). IgG anti-NR2 subunit of NMDA receptor (anti-NR2), anti-Sm, anti-RNP and anti-ribosomal P (anti-P) in sera and albumin in CSF and sera were measured by ELISA.

Results: Q albumin (CSF/serum albumin quotient) was significantly higher in acute confusional state (ACS) than in non-ACS diffuse NPSLE (anxiety disorder, cognitive dysfunction, mood disorder and psychosis) or in focal NPSLE. Serum anti-Sm, but not anti-RNP, anti-NR2 or anti-P, was significantly elevated in ACS compared with the other 2 groups of NPSLE. Accordingly, only serum anti-Sm (r=0.2655, p=0.0073), but not anti-RNP (r=0.0551), anti-NR2 (r=0.0817) or anti-P (r=0.1280), was significantly correlated with Q albumin.

Conclusion: These results confirm that the severity of BBB damages plays a crucial role in the development of ACS, the severest form of diffuse NPSLE. Moreover, the data indicate that serum anti-Sm might play a most important role in BBB breakdown in NPSLE.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/role-of-serum-autoantibodies-in-blood-brain-barrier-damages-in-neuropsychiatric-systemic-lupus-erythematosus/