BACKGROUND: Antibodies to the water channel protein aquaporin-4 (AQP4), which is expressed in astrocytic endfeet at the blood brain barrier, have been identified in the serum of Neuromyelitis optica (NMO) patients and are believed to induce damage to astrocytes. However, AQP4 specific T helper cell responses that are required for the generation of anti-AQP4 antibodies and most likely also for the formation of intraparenchymal CNS lesions have not been characterized. METHODOLOGY/PRINCIPAL FINDINGS: Using overlapping 15-meric peptides of AQP4, we identified the immunogenic T cell epitopes of AQP4 that are restricted to murine major histocompatibility complex (MHC) I-A(b).
Neuromyelitis optica (NMO) is an inflammatory disease affecting the optic nerve and spinal cord, in which autoantibodies against aquaporin 4 (AQP4) water channel protein probably play a pathogenic role. Here we show that a B-cell subpopulation, exhibiting the CD19intCD27highCD38highCD180− phenotype, is selectively increased in the peripheral blood of NMO patients and that anti-AQP4 antibodies (AQP4-Abs) are mainly produced by these cells in the blood of these patients. These B cells showed the morphological as well as the phenotypical characteristics of plasmablasts (PB) and were further expanded during NMO relapse
BACKGROUND: Anti-aquaporin-4 antibodies are believed to have a central pathogenetic role in neuromyelitis optica (NMO). B-cell activating factor (BAFF) is one of the crucial factors that determines the fate and survival of B cells and may play a role in induction of antibody-mediated autoimmunity. OBJECTIVES: To evaluate the blood and cerebrospinal fluid (CSF) levels of BAFF in NMO and multiple sclerosis (MS) patients
Background: Neuromyelitis optica (NMO) is characterized by severe optic neuritis and transverse myelitis. A disease-specific autoantibody against aquaporin (AQP) 4, mainly expressed in astrocytic foot processes, was found in the sera from patients with NMO.
Devic’s neuromyelitis optica is an inflammatory demyelinating disorder normally restricted to the optic nerves and spinal cord. Since the identification of a specific autoantibody directed against aquaporin 4, neuromyelitis optica-immunoglobulin G/aquaporin 4 antibody, neuromyelitis optica has been considered an entity distinct from multiple sclerosis
We describe two patients with recurrent longitudinally extensive transverse myelitis (LETM) associated with human T-lymphotropic virus type I or II (HTLV-I/II) exposure, and with neuromyelitis optica (NMO) immunoglobulin G (IgG) antibody in one case. HTLV-I/II are well known retroviral agents of myelopathy and B-cell dysfunction in humans.
Objective: Clinical studies indicate that anti-CD20 B-cell depletion may be an effective multiple sclerosis (MS) therapy. We investigated mechanisms of anti-CD20-mediated immune modulation using 2 paradigms of experimental autoimmune encephalomyelitis (EAE). Methods: Murine EAE was induced by recombinant myelin oligodendrocyte glycoprotein (rMOG), a model in which B cells are considered to contribute pathogenically, or MOG peptide (p)35-55, which does not require B cells.
Immune cells cross the inflamed blood–brain barrier. But it’s unclear how brain inflammation begins before immune-cell entry. Studies of a model of multiple sclerosis start to solve this ‘chicken and egg’ conundrum
Objective: To study antibody-independent contributions of B cells to inflammatory disease activity, and the immune consequences of B-cell depletion with rituximab, in patients with multiple sclerosis (MS).Methods: B-Cell effector-cytokine responses were compared between MS patients and matched controls using a 3-signal model of activation. The effects of B-cell depletion on Th1/Th17 CD4 and CD8 T-cell responses in MS patients were assessed both ex vivo and in vivo, together with pharmacokinetic/pharmacodynamic studies as part of 2 rituximab clinical trials in relapsing–remitting MS.Results: B Cells of MS patients exhibited aberrant proinflammatory cytokine responses, including increased lymphotoxin (LT):interleukin-10 ratios and exaggerated LT and tumor necrosis factor (TNF) secretion, when activated in the context of the pathogen-associated TLR9-ligand CpG-DNA, or the Th1 cytokine interferon-y, respectively
Astrocytes are specialized glial cells that outnumber neurons by over fivefold. They contiguously tile the entire central nervous system (CNS) and exert many essential complex functions in the healthy CNS
BACKGROUND: Antibodies to aquaporin-4 (AQP4) are found in a fraction of Japanese opticospinal multiple sclerosis (OSMS) patients. However, it remains unknown whether anti-AQP4 antibody-positive and negative OSMS patients possess an identical disease
Abstract Background: Neuromyelitis optica (NMO, Devic syndrome) is an inflammatory disorder of the central nervous system of putative autoimmune etiology that primarily affects the optic nerves and spinal cord. NMO is frequently associated with immunoglobulin G (IgG) antibodies to aquaporin-4 (AQP4-IgG), which are thought to be involved in the pathogenesis of the disease