Evaluation of blood-brain barrier function by quotient alpha2 macroglobulin and its relationship with interleukin-6 and complement component 3 levels in neuropsychiatric systemic lupus erythematosus

被引：27

作者：

Asano, Tomoyuki ^{[1
]}

Ito, Hiromi ^{[2
]}

Kariya, Yoshinobu ^{[2
]}

Hoshi, Kyoka ^{[2
]}

Yoshihara, Akioh ^{[3
]}

Ugawa, Yoshikazu ^{[3
]}

Sekine, Hideharu ^{[4
]}

Hirohata, Shunsei ^{[5
]}

Yamaguchi, Yoshiki ^{[6
]}

Sato, Shuzo ^{[1
]}

Kobayashi, Hiroko ^{[1
]}

Migita, Kiyoshi ^{[1
]}

Ohira, Hiromasa

Hashimoto, Yasuhiro ^{[2
,7
]}

Watanabe, Hiroshi ^{[1
]}

机构：

[1] Fukushima Med Univ, Sch Med, Dept Rheumatol, Fukushima, Japan

[2] Fukushima Med Univ, Sch Med, Dept Biochem, Fukushima, Japan

[3] Fukushima Med Univ, Sch Med, Dept Neurol, Fukushima, Japan

[4] Fukushima Med Univ, Sch Med, Dept Immunol, Fukushima, Japan

[5] Kitasato Univ, Sch Med, Dept Rheumatol & Infect Dis, Kanagawa, Japan

[6] RIKEN Global Res Cluster, RIKEN Max Planck Joint Res Ctr, Syst Glycobiol Res Grp, Struct Glycobiol Team, Wako, Saitama, Japan

[7] Fukushima Med Univ, Sch Med, Dept Gastroenterol, Fukushima, Japan

来源：

PLOS ONE | 2017年 / 12卷 / 10期

基金：

日本学术振兴会;

关键词：

CENTRAL-NERVOUS-SYSTEM; CEREBROSPINAL-FLUID; CSF BARRIER; INVOLVEMENT; DIAGNOSIS; DISEASE; CELLS; SERUM; MANIFESTATIONS; AUTOANTIBODIES;

D O I：

10.1371/journal.pone.0186414

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Although quotient of alpha2 macroglobulin (Q alpha 2MG) was previously reported to be useful for the evaluation of blood-brain barrier (BBB) function, it is not commonly used. We therefore evaluated BBB function among the various subsets of neuropsychiatric systemic lupus erythematosus (NPSLE) using quotient Q alpha 2MG. Furthermore, we determined the correlation between Q alpha 2MG and cerebrospinal (CSF) interleukin (IL)-6 level and quotient complement component 3 (Q C3). To determine intrathecal production of C3, the C3 index (Q C3/Q alpha 2MG) was also calculated. Fifty-six patients with SLE were included in this study. Of these, 48 were diagnosed with NPSLE, consisting of 30 diffuse NPSLE patients (acute confusional state (ACS): n = 14, non-ACS: n = 16) and 18 patients with focal NPSLE. CSF IL-6 concentration, and paired serum and CSF levels of alpha 2MG and C3, were measured by enzymelinked immuno solvent assay (ELISA). The Q alpha 2MG, Q C3, and C3 index were then calculated. Q alpha 2MG, Q C3, and IL-6 concentrations in the CSF were significantly elevated in NPSLE compared with non-NPSLE. Among the subsets of NPSLE, significant increases in Q alpha 2MG, CSF IL-6, and Q C3 were observed in ACS compared with non-ACS or focal NPSLE. There was a positive correlation between CSF IL-6 level and Q alpha 2MG, as well as between Q C3 and Q alpha 2MG, in diffuse NPSLE. There were no significant differences in C3 index between NPSLE and non-NPSLE, as well as among the subgroups of NPSLE. Our study suggests that BBB disruption is present in ACS, and elevated levels of IL-6 and C3 in CSF in diffuse NPSLE, especially in ACS, might result from their entry to the CSF from the systemic circulation through the damaged BBB, as well as increased intrathecal production. Furthermore, Q alpha 2MG might be useful for the evaluation of BBB integrity.

引用

页数：18

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