Interferon-free, guideline-tailored therapy with direct-acting antivirals is highly effective and safe for HCV-associated MC patients; the overall 100% rate of clinical response of vasculitis, on an intention-to-treat basis, opens the perspective for curing the large majority of these so far difficult-to-treat patients. (Hepatology 2016;64:1473-1482).

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Chemokine and chemokine receptors expressed by normal and neoplastic lymphocytes play a key role in cell recruitment into skin and lymph nodes. The aim of this study was to get further insights into the role of chemokines in pathogenesis and progression of cutaneous T-cell lymphoma (CTCL) with particular regard to Sézary Syndrome (SS), a CTCL variant with blood involvement. Here, we show that functional CXCL13 homeostatic chemokine is strongly up-regulated in SS cells, well-detectable in skin lesions and lymph nodes, and measurable at high concentration in plasma of SS patients, at different levels during disease progression. Furthermore, we show that the addition of CXCL13 to CCL19 or to CCL21, the selective CCR7 agonists responsible for lymph node homing, strongly enhances the migration of CCR7+ SS cells. We also show that neutralization of the CCR7 receptor strongly impairs CCL19/21-induced chemotaxis of SS cells both in the absence or presence of CXCL13. Additional experiments performed to investigate the survival, adhesion, and metalloproteases secretion indicate that CXCL13 combined with CCL19 and CCL21 mainly affects the chemotaxis of SS cells. Our findings suggest that this newly described CXCL13 expression in SS represents a new pathogenetic mechanism of diagnostic significance. [Cancer Res 2008;68(17):7137-46]

In IgA nephropathy, abnormal O-glycosylation of IgA1 molecules contributes to mesangial IgA1 deposition and the development of glomerular injury; however, direct in situ demonstration of aberrantly O-glycosylated IgA1 within glomerular immune deposits has not been reported. This study investigated the presence of abnormally glycosylated IgA1 in situ and its spatial relationship with complement within the immune deposits and correlated these features with glomerular lesion severity. Immunofluorescence and confocal microscopy were used to evaluate 19 consecutive renal biopsies, and the severity of glomerular lesions were also scored. Aberrantly glycosylated IgA was observed within the immune deposits, and its amount was found to correlate with both the severity of glomerular lesions and the amount of C3c on the surface of the deposits. These results demonstrate that qualitative and quantitative evaluation of aberrantly glycosylated IgA can be performed on routine renal biopsy samples. Its presence in immune deposits likely influences the spatial organization of IgA and C3c, thereby contributing to the glomerular inflammatory response in IgA nephropathy.

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b-Catenin is a ubiquitously cytoplasmic protein that has a critical role in embryonic development and mature tissue homeostasis through its effects on E-cadherin-mediated cell adhesion and Wnt-dependent signal transduction. Mutations that alter specific b-catenin residues important for GSK-3b phosphorylation, or increase the half-life of the protein, were identified in human cancer. However, the role of the Wnt pathway in B-and T-cell oncogenesis has not been extensively investigated. To assess the role of b-catenin defects in primary cutaneous lymphomas, we examined the expression pattern and the genetic alteration of b-catenin on 79 samples from 74 patients with primary cutaneous lymphomas from B-and T-cell origin. Immunohistochemical analysis revealed b-catenin deregulation in five primary cutaneous B-cell lymphomas (21%) and in 21 primary cutaneous T-cell lymphomas (42%) without nuclear accumulation suggesting that activation and accumulation of b-catenin may play an important role in the development of skin lymphomas. Mutation analysis of b-catenin exon 3, which included the responsible element for Wnt signaling, was therefore done in 19 samples. However, genetic alterations of b-catenin exon 3 were not detected in any of these cases suggesting that other regulatory mechanisms may be relevant in activating b-catenin signaling in cutaneous lymphomas.

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