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

Abstract

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)-γ and the proportion of circulating memory and CD19(+)CD24(high)CD38(high) regulatory B cells were evaluated by flow cytometry. The cerebrospinal fluid (CSF) levels of BAFF and CXCL13 were determined by enzyme-linked immunosorbent assay (ELISA).

RESULTS:

The CD19(+)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 CD19(+)CD24(high)CD38(high) regulatory B cell levels were even lower than in AQP4-ab-negative NMO patients. The CSF BAFF and CXCL13 levels were significantly higher in NMO patients than in patients with RRMS and other non-inflammatory neurologic diseases (ONDs).

CONCLUSIONS:

The immuno-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 CXCL13 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.

• Authors: Chao Quan, Hai Yu, Jian Qiao, Baoguo Xiao, Guixian Zhao, Zhiying Wu, Zhenxin Li, Chuanzhen Lu
• Journal: Multiple sclerosis (Houndmills, Basingstoke, England) (Mult Scler) Vol. 19 Issue 3 Pg. 289-98 (Mar 2013) ISSN: 1477-0970 [Electronic] England
• PMID: 22864301 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)

Topics

• Adolescent
• Adult
• Aged
• Antibody Specificity
• B-Lymphocyte Subsets (immunology, metabolism, pathology)
• Diagnosis, Differential
• Humans
• Lymphocyte Activation (immunology)
• Male
• Middle Aged
• Multiple Sclerosis (cerebrospinal fluid, immunology, pathology)
• Neuromyelitis Optica (cerebrospinal fluid, immunology, pathology)
• Spinal Cord (immunology, pathology)
• Up-Regulation (immunology)
• Young Adult