Behçhet disease (BD) is a rare, systemic, inflammatory disorder with multiorgan damage and various clinical manifestations such as oral ulcers, genital ulcers and uveitis. Pathogenesis is still unknown. BD is currently considered a rheumatic disorder with some features of both autoimmune and autoinflammatory conditions. Additionally, some authors have recently proposed to classify BD as ‘MHC-I-opathy’. Despite HLA-B51 and some gene polymorphisms have been associated with BD, diagnosis is based on clinical parameters and currently laboratory tests are only of a little help. The aims of this study were: 1) to increase the knowledge about BD pathogenesis; 2) to identify laboratory tests which can support BD diagnosis; 3) to identify potential therapeutic targets for BD treatment. In details, based on the hypothesis that impaired cytotoxicity mechanisms of circulating Natural Killer (NK), NKT and T cells might have a role in the pathogenesis of BD, the first part of the study was aimed to identify a specific profile of circulating NK, NKT and T cells able to discriminate between BD patients and healthy controls, by investigating the phenotypic characteristics, the cytotoxic potential of circulating NK and NKT cells, and by quantifying 27 plasmatic cytokines/chemokines. The second part of the study was focused on BD-related uveitis, which may cause irreversible ocular structural changes and permanent damage in sensory retina with visual loss, if left untreated. The therapeutic armamentarium for BD uveitis is very limited. The aim of this part of the study was to investigate differences in the mechanisms of two distinct types of endogenous uveitis (i.e. BD uveitis versus Vogt-Koyanagi-Harada disease, VKH-related uveitis) - to search for potential markers and therapeutic targets. Levels of pro- and antiinflammatory cytokines were measured in aqueous humor from patients with active BD uveitis and VKH. Secondly, given the evidence about the impairment of cytotoxicity mechanisms in BD, a different distribution of NK cell subsets in the aqueous humor of patients with different types of endogenous uveitis could also be hypothesised. With this aim, frequency of NK and NKT cells in the same groups of patients has been explored.

Immunological profiling of peripheral blood mononuclear cells and aqueous humor in Behçet disease / Alessandra Soriano - : . , 2018 Apr 26. ((30. ciclo

Immunological profiling of peripheral blood mononuclear cells and aqueous humor in Behçet disease

2018-04-26

Abstract

Behçhet disease (BD) is a rare, systemic, inflammatory disorder with multiorgan damage and various clinical manifestations such as oral ulcers, genital ulcers and uveitis. Pathogenesis is still unknown. BD is currently considered a rheumatic disorder with some features of both autoimmune and autoinflammatory conditions. Additionally, some authors have recently proposed to classify BD as ‘MHC-I-opathy’. Despite HLA-B51 and some gene polymorphisms have been associated with BD, diagnosis is based on clinical parameters and currently laboratory tests are only of a little help. The aims of this study were: 1) to increase the knowledge about BD pathogenesis; 2) to identify laboratory tests which can support BD diagnosis; 3) to identify potential therapeutic targets for BD treatment. In details, based on the hypothesis that impaired cytotoxicity mechanisms of circulating Natural Killer (NK), NKT and T cells might have a role in the pathogenesis of BD, the first part of the study was aimed to identify a specific profile of circulating NK, NKT and T cells able to discriminate between BD patients and healthy controls, by investigating the phenotypic characteristics, the cytotoxic potential of circulating NK and NKT cells, and by quantifying 27 plasmatic cytokines/chemokines. The second part of the study was focused on BD-related uveitis, which may cause irreversible ocular structural changes and permanent damage in sensory retina with visual loss, if left untreated. The therapeutic armamentarium for BD uveitis is very limited. The aim of this part of the study was to investigate differences in the mechanisms of two distinct types of endogenous uveitis (i.e. BD uveitis versus Vogt-Koyanagi-Harada disease, VKH-related uveitis) - to search for potential markers and therapeutic targets. Levels of pro- and antiinflammatory cytokines were measured in aqueous humor from patients with active BD uveitis and VKH. Secondly, given the evidence about the impairment of cytotoxicity mechanisms in BD, a different distribution of NK cell subsets in the aqueous humor of patients with different types of endogenous uveitis could also be hypothesised. With this aim, frequency of NK and NKT cells in the same groups of patients has been explored.
Behçet disease; NK cells; NKT cells; aqueous humor; uveitis
Immunological profiling of peripheral blood mononuclear cells and aqueous humor in Behçet disease / Alessandra Soriano - : . , 2018 Apr 26. ((30. ciclo
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/20.500.12610/68772
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