Impaired regulatory function and enhanced intrathecal activation of B cells in neuromyelitis optica: distinct from multiple sclerosis

Impaired regulatory function and enhanced intrathecal activation of B cells in neuromyelitis optica: distinct from multiple sclerosis
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视神经脊髓炎中 B 细胞的调节功能受损和鞘内激活增强:与多发性硬化症不同

DOI:
10.1177/1352458512454771
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发表时间:
2013-03-01
影响因子:
5.8
通讯作者:
Lu, Chuanzhen
Lu, Chuanzhen
中科院分区:
医学2区
文献类型:
--
作者:
Quan, Chao;Yu, Hai;Lu, Chuanzhen

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Background: The effective treatment of neuromyelitis optica (NMO) with rituximab has suggested an important role for B cells in NMO pathogenesis.Objective:To explore the antibody-independent function of B cells in NMO and relapsing remitting multiple sclerosis (RRMS).Methods: Fifty-one NMO patients and 42 RRMS patients in an acute relapse phase and 37 healthy controls (HC) were enrolled in the study. The B cell expression of B cell activating factor receptor (BAFF-R), CXCR5 and very late antigen-4 (VLA-4), the B cell production of interleukin (IL)-10 and interferon (IFN)-gamma and the proportion of circulating memory and CDI9(+)CD24(high)CD38(high) regulatory B cells were evaluated by flow cytometry. The cerebrospinal fluid (CSF) levels of BAFF and CXCLI3 were determined by enzyme-linked immunosorbent assay (ELISA).Results:The CDI9(+)CD24(high)CD38(high) regulatory B cell levels and the B cell expression of IL-10 were significantly lower in NMO patients than in RRMS patients and the HC. In aquaporin-4 antibody (AQP4-ab)-positive NMO patients, the B cell IL-10 production and CDI9+CD24highCD38high regulatory B cell levels were even lower than in AQP4-ab-negative NMO patients.The CSF BAFF and CXCL I 3 levels were significantly higher in NMO patients than in patients with RRMS and other non-inflammatory neurologic diseases (ONDs).Conclusions: The imnnuno-regulatory properties of B cells are significantly impaired in NMO patients and particularly in AQP4-ab-positive NMO patients.The elevated CSF levels of BAFF and CXCLI3 in NMO suggest an enhanced intrathecal B cell recruitment and activation. Our results further define the distinct immunological nature of NMO and RRMS from the B cell perspective.