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.jpg): Failed to open stream: No such file or directory in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 117 Arthritis+Res+Ther
2014 ; 16
(2
): R77
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Blood-brain barrier damages and intrathecal synthesis of
anti-N-methyl-D-aspartate receptor NR2 antibodies in diffuse
psychiatric/neuropsychological syndromes in systemic lupus erythematosus
#MMPMID24655341
Hirohata S
; Arinuma Y
; Yanagida T
; Yoshio T
Arthritis Res Ther
2014[Mar]; 16
(2
): R77
PMID24655341
show ga
INTRODUCTION: Although neuropsychiatric systemic lupus erythematosus (NPSLE) is
one of the recalcitrant complications of the disease, its pathogenesis still
remains unclear. Previous studies revealed that antibodies reactive with NMDA
(N-methyl-D-aspartate) receptor NR2 (anti-NR2) are elevated in cerebrospinal
fluid (CSF) of patients with diffuse psychiatric/neuropsychological syndromes
(diffuse NPSLE), which is usually more recalcitrant than neurologic syndromes of
NPSLE (focal NPSLE). Two mechanisms have been implicated for the elevation of CSF
IgG, including intrathecal synthesis and transudation through the damaged
blood-brain barrier (BBB). The present study was designed in order to elucidate
the roles of BBB function and intrathecal synthesis of anti-NR2 in the elevation
of CSF anti-NR2 with regard to the severity in NPSLE. METHODS: Paired serum and
CSF samples were obtained from 81 systemic lupus erythematosus (SLE) patients
when they presented active neuropsychiatric manifestations, and from 22 non-SLE
control patients with non-inflammatory neurological diseases. The 81 SLE patients
consisted of 55 patients with diffuse NPSLE, including 23 patients with acute
confusional state (ACS), the severest form of diffuse NPSLE, and 26 patients with
neurologic syndromes or peripheral nervous system involvement (focal NPSLE). IgG
anti-NR2 and albumin were measured by ELISA. BBB function and intrathecal
synthesis of anti-NR2 were evaluated by Q albumin and by CSF anti-NR2 index,
respectively. RESULTS: CSF anti-NR2 levels, Q albumin and CSF anti-NR2 index were
significantly higher in NPSLE than in non-SLE control. CSF anti-NR2 levels and Q
albumin were significantly higher in ACS than in non-ACS diffuse NPSLE (anxiety
disorder, cognitive dysfunction, mood disorder and psychosis) or in focal NPSLE,
whereas there was no significant difference in CSF anti-NR2 index among the 3
groups. CSF anti-NR2 levels were significantly correlated with Q albumin in
diffuse NPSLE (r?=?0.3754, P?=?0.0053). CONCLUSIONS: These results demonstrate
that the severity of BBB damages plays a crucial role in the development of ACS,
the severest form of diffuse NPSLE, through the accelerated entry of larger
amounts of anti-NR2 into the central nervous system.
|Adult
[MESH]
|Autoantibodies/*cerebrospinal fluid
[MESH]
|Autoantigens/immunology
[MESH]
|Blood-Brain Barrier/*pathology
[MESH]
|Cerebrospinal Fluid/immunology
[MESH]
|Enzyme-Linked Immunosorbent Assay
[MESH]
|Female
[MESH]
|Humans
[MESH]
|Lupus Vasculitis, Central Nervous System/cerebrospinal
fluid/*immunology/pathology
[MESH]