Vidalino, Laura (2008) Espressione di membrana della serpina SCCA e deregolazione dei linfociti B: studio in pazienti con infezione virale ed in pazienti con Lupus Eritematoso sistemico. [Ph.D. thesis]
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Background.HCV infection may progress to a broad spectrum of liver diseases, as a consequence of complex interactions between viral and host factors. The role of B cells in HCV infection is largely unknown. Systemic Lupus erythematosus (SLE) is a systemic autoimmune disease. B cell deregulation represents a central feature both of HCV infection and SLE. SCCA, an ov-serpin, found in majority of primary liver cancers, is detectable in lymphocytes. To date, the potential involvement of SCCA in the pathogenesis of SLE and in HCV have not yet been investigated.
Aim. To characterize SCCA expression in peripheral blood mononuclear cells (PBMC) in HCV infected and in SLE patients.
Patients and methods. 45 HCV patients (14 with chronic hepatitis, 17 with cirrhosis and 14 with hepatocellular carcinoma), 12 with LES and 24 healthy controls were analyzed. Surface expression of SCCA in PBMC was assessed by FACS analysis. To define SCCA co-expression in B lymphocytes, different activation molecules (CD27, CD69, CD71, CD86 and CXCR3) were simultaneously evaluated. In purified B cells, SCCA RNA was quantified by Real Time PCR and localization of SCCA was defined by confocal microscopy.
Results. FACS analysis and confocal microscopy showed that SCCA was expressed on the surface of B lymphocytes in 68% of normal subjects and in 32% of HCV patients (p<0.03). In SLE patients SCCA resulted not expressed in any of the patients (p=0.0000). Real Time PCR confirmed higher levels of transcription of the serpin in purified B cells of control subjects (p=0.0041). SCCA positivity was significantly associated with CD27 reactivity.
Conclusions. HCV infection is associated with a marked reduction of SCCA being associated with the memory B cells molecule CD27 on B lymphocytes surface, suggesting a possible involvement of SCCA in B cell defects in HCV and in SLE. In SLE patients the serpin is not expressed on the surface of B lymphocytes. These findings suggest a possible involvement of SCCA in the deregulation of B cell reactivity, during HCV infection and SLE.
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