RESUMO
Dyspareunia and vulvodynia are genital pain disorders that have devastating effects on women's quality of life. These disorders occur with high prevalence and place a significant financial burden on women and the health care system. Many women do not report genital pain, and most providers do not inquire about this type of pain. As a result, women also experience social isolation. Numerous treatments are thought to improve quality of life and decrease pain; however, more studies are needed. This review aims to provide an overview of clinical evaluation methods and to summarize treatment options for women suffering from dyspareunia and vulvodynia.
RESUMO
Neuromyelitis optica (NMO) is an inflammatory demyelinating disease that predominantly affects the optic nerves and spinal cord. Recombinant antibodies (rAbs) generated from clonally expanded plasma cells in an NMO patient are specific to AQP4 and pathogenic. We screened phage-displayed peptide libraries with these rAbs, and identified 14 high affinity linear and conformational peptides. The linear peptides shared sequence homologies with NMO autoantigen AQP4 on the extracellular surface. Competitive inhibition ELISA and immunocytochemistry demonstrated that these peptides represent epitopes of NMO autoantigen AQP4. Peptide epitopes/mimotopes may have potential uses for disease prognosis, monitoring, and therapy.
Assuntos
Autoanticorpos/metabolismo , Marcação de Genes/métodos , Neuromielite Óptica/metabolismo , Fragmentos de Peptídeos/metabolismo , Sequência de Aminoácidos , Animais , Autoanticorpos/genética , Humanos , Imunoglobulina G/genética , Imunoglobulina G/metabolismo , Dados de Sequência Molecular , Neuromielite Óptica/genética , Fragmentos de Peptídeos/genética , Biblioteca de Peptídeos , Ratos , Ratos Endogâmicos F344 , Sindecana-1/genética , Sindecana-1/metabolismoRESUMO
OBJECTIVE: The serum of most neuromyelitis optica (NMO) patients contains autoantibodies (NMO-IgGs) directed against the aquaporin-4 (AQP4) water channel located on astrocyte foot processes in the perivessel and subpial areas of the brain. Our objectives were to determine the source of central nervous system (CNS) NMO-IgGs and their role in disease pathogenesis. METHODS: Fluorescence-activated cell sorting and single-cell reverse transcriptase polymerase chain reaction were used to identify overrepresented plasma cell immunoglobulin (Ig) sequences in the cerebrospinal fluid (CSF) of an NMO patient after a first clinical attack. Monoclonal recombinant antibodies (rAbs) were generated from the paired heavy and light chain sequences and tested for target specificity and Fc effector function. The effect of CSF rAbs on CNS immunopathology was investigated by delivering single rAbs to rats with experimental autoimmune encephalomyelitis (EAE). RESULTS: Repertoire analysis revealed a dynamic, clonally expanded plasma cell population with features of an antigen-targeted response. Using multiple independent assays, 6 of 11 rAbs generated from CSF plasma cell clones specifically bound to AQP4. AQP4-specific rAbs recognized conformational epitopes and mediated both AQP4-directed antibody-dependent cellular cytotoxicity and complement-mediated lysis. When administered to rats with EAE, an AQP4-specific NMO CSF rAb induced NMO immunopathology: perivascular astrocyte depletion, myelinolysis, and complement and Ig deposition. INTERPRETATION: Molecular characterization of the CSF plasma cell repertoire in an early NMO patient demonstrates that AQP4-specific Ig is synthesized intrathecally at disease onset and directly contributes to CNS pathology. AQP4 is now the first confirmed antigenic target in human demyelinating disease.