title: Role of BAFF in Opsoclonus-Myoclonus syndrome, a bridge between cancer and autoimmunity.
abstract: OMS is a rare paraneoplastic disorder that affects adults and children. Pediatric OMS is often associated with NB, a common, solid tumor of childhood, derived from the sympathetic nervous system. The detection of autoantibodies and lymphocytic infiltration in NB patients led to advance an autoimmune hypothesis for the pathogenesis of OMS-related NB. BAFF is a potent modulator of B cell growth and survival upon interaction with its receptors BAFF-R and BCMA. The aim of this study was to investigate mechanism(s) involved in ectopic lymphoid neogenesis in OMS-associated NB. We investigated BAFF, BAFF-R, and BCMA expression in NB tumors associated or not with OMS. Furthermore, we evaluated BAFF expression and secretion in NB cell lines, treated or untreated with differentiating agents. Immunohistochemically, lymphocytes infiltrating NB tumors from patients, with or without OMS, expressed BAFF, BAFF-R, and BCMA, whereas neuroblasts expressed BAFF and BCMA but not BAFF-R. By flow cytometry, BAFF was found to be consistently expressed in NB cell lines. Similarly to the results obtained in tissue lesions, BCMA but not BAFF-R was detected on the surface of all NB cell lines under basal conditions. De novo synthesis of BAFF-R and up-regulation of BCMA were observed in NB cell lines upon treatment with IFN-γ or 13-cis retinoic acid. This study provides new insights in the mechanisms driving the neogenesis of lymphoid follicles and in the functional interactions between tumor and immune cells in OMS-associated NB.
authors.affiliation: Laboratories of Oncology, Istituto Giannina Gaslini, Genoa, Italy.
authors.forename: Lizzia
authors.initials: L
authors.lastname: Raffaghello
authors.forename: Verena
authors.initials: V
authors.lastname: Fuhlhuber
authors.forename: Giovanna
authors.initials: G
authors.lastname: Bianchi
authors.forename: Massimo
authors.initials: M
authors.lastname: Conte
authors.forename: Franz
authors.initials: F
authors.lastname: Blaes
authors.forename: Claudio
authors.initials: C
authors.lastname: Gambini
authors.forename: Vito
authors.initials: V
authors.lastname: Pistoia
mesh_terms: D000328:Adult; D000998:Antiviral Agents / Q000494:pharmacology; D015551:Autoimmunity; D053264:B-Cell Activating Factor / Q000378:metabolism*; D053265:B-Cell Activation Factor Receptor / Q000378:metabolism*; D053301:B-Cell Maturation Antigen / Q000378:metabolism*; D002454:Cell Differentiation / Q000187:drug effects; D002478:Cells, Cultured; D002648:Child; D002675:Child, Preschool; D003879:Dermatologic Agents / Q000494:pharmacology; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D007124:Immunoenzyme Techniques; D007223:Infant; D007371:Interferon-gamma / Q000494:pharmacology; D015474:Isotretinoin / Q000494:pharmacology; D008214:Lymphocytes / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D008297:Male; D009447:Neuroblastoma / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D053578:Opsoclonus-Myoclonus Syndrome / Q000276:immunology / Q000378:metabolism* / Q000473:pathology
chemical_list: D000998:Antiviral Agents; D053264:B-Cell Activating Factor; D053265:B-Cell Activation Factor Receptor; D053301:B-Cell Maturation Antigen; D003879:Dermatologic Agents; C435926:TNFRSF13C protein, human; C086966:TNFRSF17 protein, human; C505719:TNFSF13B protein, human; D007371:Interferon-gamma; D015474:Isotretinoin
keywords: B lymphocytes; mechanisms of intratumor lymphoid neogenesis; neuroblastoma; paraneoplastic syndrome