RESUMO
Mendelian Susceptibility to Mycobacterial Disease (MSMD) is a rare syndrome with infections-among other complications-after Bacillus Calmette-Guerin (BCG) vaccination in children. We focused on the IL-12/IFN-γ pathway to identify new mutations in our patients. This study included 20 patients by vulnerability to mycobacteria and clinical manifestations of severe, recurrent infections. Blood samples were activated with BCG, BCG + IL-12 and BCG + IFN-γ. Cytokine levels were analyzed by ELISA. Measurements of IL-12Rß1 and IL-12Rß2 on the surface of peripheral blood mononuclear cells were performed by flow cytometry. To detect genetic defects, next-generation sequencing was performed by Thermo Fisher immunodeficiency panel. Flow cytometry analysis of 20 patients indicated reduction in IL-12R (ß1/ß2) expression in seven patients who showed incomplete production of IFN-γ by ELISA. In the patient with reduced IL-12 production, IFN-γR and IL-12R (ß1/ß2) expression levels were normal. Mutation analysis showed three previously reported mutations, two novel mutations in IL-12 R (ß1/ß2), and one previously reported mutation in IL-12.
Assuntos
Leucócitos Mononucleares/imunologia , Mutação , Mycobacterium bovis/imunologia , Receptores de Interleucina-12/genética , Tuberculose/genética , Feminino , Citometria de Fluxo , Humanos , Lactente , Subunidade p35 da Interleucina-12/genética , Subunidade p40 da Interleucina-12/genética , Masculino , Receptores de Interferon/genética , Receptores de Interleucina-12/análise , Transdução de Sinais , Receptor de Interferon gamaRESUMO
Angiogenesis and metastasis are two critical steps for cancer cells survival and migration. The microenvironment of tumor sphere induces new blood vessels formation for enhancing tumor mass. Preexisting capillaries and postcapillary venules in tumors bring about new blood vessels. ROBO1-ROBO4 are transmembrane receptors family which act as guidance molecules of the nervous system. The SLITs family is secreted glycoproteins that bind to these receptors. SLIT-ROBO signaling pathway plays an important role in neurogenesis and immune response. Linkage between ROBOs and their ligands (SLITs) induce chemorepllent signal for regulation of axon guidance and leukocyte cell migration, recent finding shows that it is also involved in endothelial cell migration and angiogenesis in various type of cancers. In this article we review recent finding of SLIT-ROBO pathway in angiogenesis and metastasis.
