title: Changes in B and T-cell subsets and NMO-IgG levels after immunoglobulins and rituximab treatment for an acute attack of neuromyelitis optica.
abstract: BACKGROUND
  There is increasing evidence supporting that neuromyelitis optica (NMO) is an inflammatory humoral mediated disorder associated with NMO-IgG/AQP-4 antibodies. However, little is known about the subsets of B cells and T cells that contribute to the pathogenesis or therapy response.
  
  
  OBJECTIVE
  To describe the clinical and immunological changes associated with intravenous immunoglobulins (IV-Igs) plus rituximab (RTX) in a patient with a severe acute attack of NMO and intrathecal synthesis of NMO-IgG/AQP-4, who previously did not respond to intravenous methylprednisolone and plasma exchange.
  
  
  METHODS
  We sequentially analysed the levels of NMO-IgG/AQP-4 by immunohistochemistry, and B and T cells subsets by multiparametric flow-cytometry, in the CSF and peripheral blood (PB), before and alter IV-Igs plus RTX therapy.
  
  
  RESULTS
  In the CSF before treatment, and compared with PB, there was a higher percentage of CD4(+) T cells and a lower percentage of CD8(+) T cells and CD19(+) B cells. After therapy, the percentage of CD4(+) T cells remained high, and that of CD8(+) T cells increased. The observed decrease in the percentage of CD19(+) B cells was lower than in the PB. When the CSF was compared, it was found that the percentage of effector-memory and effector CD8(+) T cells had increased after therapy, and that of IgM memory B cells and switched-memory B cells decreased. The observed changes paralleled the decrease of NMO-IgG/AQP-4 results to negative and the clinical improvement.
  
  
  CONCLUSIONS
  Our findings confirm that, besides intrathecal humoral immune response against AQP4, B and T cell subsets are involved in the modulation of inflammation within and outside the central nervous system.
authors.affiliation: Servicio de Neurología, Hospital General Universitario Gregorio Marañón, Madrid, España. Electronic address: claradeandres@hotmail.com.
authors.forename: C
authors.initials: C
authors.lastname: de Andrés
authors.affiliation: Servicio de Inmunología, Hospital General Universitario Gregorio Marañón, Madrid, España.
authors.forename: R
authors.initials: R
authors.lastname: Teijeiro
authors.affiliation: Servicio de Neurología, Hospital Clínico e Institut d́Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, España.
authors.forename: A
authors.initials: A
authors.lastname: Saiz
authors.affiliation: Servicio de Neuroradiología, Hospital General Universitario Gregorio Marañón, Madrid, España.
authors.forename: P
authors.initials: P
authors.lastname: Fernández
authors.affiliation: Servicio de Inmunología, Hospital General Universitario Gregorio Marañón, Madrid, España.
authors.forename: S
authors.initials: S
authors.lastname: Sánchez-Ramón
mesh_terms: D000293:Adolescent; D051401:Aquaporin 4 / Q000276:immunology*; D001323:Autoantibodies / Q000097:blood; D016175:B-Lymphocyte Subsets / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D016756:Immunoglobulins, Intravenous / Q000627:therapeutic use*; D007155:Immunologic Factors / Q000627:therapeutic use*; D009471:Neuromyelitis Optica / Q000134:cerebrospinal fluid / Q000188:drug therapy / Q000276:immunology*; D000069283:Rituximab / Q000627:therapeutic use*; D013116:Spinal Cord / Q000276:immunology / Q000473:pathology; D016176:T-Lymphocyte Subsets / Q000276:immunology*
chemical_list: C496030:AQP4 protein, human; D051401:Aquaporin 4; D001323:Autoantibodies; D016756:Immunoglobulins, Intravenous; D007155:Immunologic Factors; D000069283:Rituximab
keywords: Anti-aquaporin-4 autoantibodies; Autoanticuerpos Anti-acuaporina-4; CD19(+) and CD8(+) T cell subsets; Cerebrospinal fluid; Líquido cefalorraquídeo; Neuromielitis óptica; Neuromyelitis optica; Subclases de células B CD19(+) y T CD8(+)