Our study indicates that the addition of rituximab to conventional therapy in patients with MMP results in more rapid and sustained disease control with potentially fewer adverse events.

Pemphigus vulgaris (PV) is an autoimmune epidermal blistering disease in which autoantibodies (IgG) are directed against the desmosomal cadherin desmoglein 3 (Dsg3). In order to better understand how PV IgG alters desmosome morphology and function in vivo, PV patient biopsies were analyzed by structured illumination microscopy (SIM), a form of super-resolution fluorescence microscopy. In patient tissue, desmosomal proteins were aberrantly clustered and localized to PV IgG-containing endocytic linear arrays. Patient IgG also colocalized with markers for lipid rafts and endosomes. Additionally, steady-state levels of Dsg3 were decreased and desmosomes were reduced in size in patient tissue. Desmosomes at blister sites were occasionally split, with PV IgG decorating the extracellular faces of split desmosomes. Desmosome splitting was recapitulated in vitro by exposing cultured keratinocytes both to PV IgG and to mechanical stress, demonstrating that splitting at the blister interface in patient tissue is due to compromised desmosomal adhesive function. These findings indicate that Dsg3 clustering and endocytosis are associated with reduced desmosome size and adhesion defects in PV patient tissue. Further, this study reveals that super-resolution optical imaging is powerful approach for studying epidermal adhesion structures in normal and diseased skin.

The present findings show that in the rat, changes in cardiovascular responsiveness occur after a brief period of uraemia which are similar to those observed in patients and rats with chronic renal failure.

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