title: 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.affiliation: Department of Neurology, Huashan Hospital, Shanghai Medical College, Fudan University, Shanghai, China.
authors.forename: Chao
authors.initials: C
authors.lastname: Quan
authors.forename: Hai
authors.initials: H
authors.lastname: Yu
authors.forename: Jian
authors.initials: J
authors.lastname: Qiao
authors.forename: Baoguo
authors.initials: B
authors.lastname: Xiao
authors.forename: Guixian
authors.initials: G
authors.lastname: Zhao
authors.forename: Zhiying
authors.initials: Z
authors.lastname: Wu
authors.forename: Zhenxin
authors.initials: Z
authors.lastname: Li
authors.forename: Chuanzhen
authors.initials: C
authors.lastname: Lu
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000918:Antibody Specificity; D016175:B-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism / Q000473:pathology*; D003937:Diagnosis, Differential; D006801:Humans; D008213:Lymphocyte Activation / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000134:cerebrospinal fluid / Q000276:immunology* / Q000473:pathology*; D009471:Neuromyelitis Optica / Q000134:cerebrospinal fluid / Q000276:immunology* / Q000473:pathology*; D013116:Spinal Cord / Q000276:immunology / Q000473:pathology; D015854:Up-Regulation / Q000276:immunology*; D055815:Young Adult