RESUMO
Retroperitoneal fibrosis (RPF) is a rare disease characterized by the presence of fibro-inflammatory tissue around the aorta entrapping the adjacent structures. RPF can be idiopathic or secondary to many disorders. The physiopathology is unknown but can be part of the spectrum of IgG4 related diseases. Imaging studies and inflammatory markers are essential for initial evaluation and follow-up. Biopsy is usually not recommended. The first line of treatment is corticosteroids associated or not with immunosuppressive drugs. In case of ureteral obstruction with renal failure, ureteral stent placement or nephrostomies are recommended. Initial response to treatment is usually good but relapses are frequent.
Assuntos
Fibrose Retroperitoneal , Doenças Autoimunes/diagnóstico , Doenças Autoimunes/terapia , Biomarcadores/análise , Biomarcadores/sangue , Biópsia , Diagnóstico Diferencial , Glucocorticoides/uso terapêutico , Humanos , Doença Relacionada a Imunoglobulina G4/diagnóstico , Doença Relacionada a Imunoglobulina G4/terapia , Imunossupressores/uso terapêutico , Doenças Raras , Fibrose Retroperitoneal/complicações , Fibrose Retroperitoneal/diagnóstico , Fibrose Retroperitoneal/patologia , Fibrose Retroperitoneal/terapiaRESUMO
BACKGROUND: Mammalian target of rapamycin complex 1 (mTORC 1) drives the proinflammatory expansion of T helper (TH) type 1, TH17â¯cells and controls fibroblast proliferation, typical features of large vessel vasculitis (LVV) pathogenesis. Molecular pathways involved in arterial lesions of LVV are unknown. METHODS: We evaluate mTORC pathway activation in vascular aorta lesions and in T cell homeostasis of patients with LVV. RESULTS: Proliferation of both endothelial cells and vascular smooth-muscle cells was shown in vascular lesions in LVV. The vascular endothelium of proliferating aorta vessels from patients with LVV showed indications of activation of the mTORC1 pathway (S6RP phosphorylation). In cultured vascular endothelial cells, sera from patients with LVV stimulated mTORC1 through the phosphorylation of S6RP. mTORC1 activation was found also in Th1 and Th17â¯cells both systemically and in inflamed vessels. Patients with LVV exhibited a diminished S6RP phosphorylation in Tregs. Inhibition of mTORC1 pathway with rapamycin, increase Tregs and decrease effector CD4+IFNγ+, CD4+IL17+ and CD4+IL21+ T cells in patients with LVV. CONCLUSIONS: We provided evidence that mTORC1 pathway has a central role in driving T cell inflammation and vascular lesions in LVV. Targeting mTORC pathway may represent a new therapeutic option in patients with LVV.
